Risk factors for humanized IgG1 monoclonal antibody in the treatment of Crohn's disease: pharmacovigilance of the FDA adverse event reporting system (FAERS)

Risk factors for humanized IgG1 monoclonal antibody in the treatment of Crohn's disease: pharmacovigilance of the FDA adverse event reporting system (FAERS) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk factors for humanized IgG1 monoclonal antibody in the treatment of Crohn's disease: pharmacovigilance of the FDA adverse event reporting system (FAERS) Jiangchuan Xie, Chun Tao, Linli XIE, Yongchuan Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6189305/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Ustekinumab and risankizumab, humanized IgG1 monoclonal antibody that selectively inhibits interleukin(IL)-23/IL-12 and IL-23, respectively, is currently approved for treating Crohn’s disease(CD). This study identified and characterized adverse events (AEs) significantly related to IgG1 monoclonal antibodies in treating CD and compared the differences between the two drugs to provide clinical reference. Methods AEs reports were collected from the United States Food and Drug Administration Adverse Event Reporting System(FAERS). Ustekinumab’s AEs were collected from the third quarter of 2016 to the second quarter of 2024, while risankizumab’s AEs were collected from the second quarter of 2022 to the second quarter of 2024. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to assess the reporting of AEs induced by ustekinumab and risankizumab in treating CD. When the lower limit of the 95% confidence interval (CI) of ROR > 1.0 and PRR ≥ 2 with an associated χ2 value of 4 or more was considered the threshold for a signal. Results A total of 2,5223 AE reports were retrieved from FAERS, with 1,9753 for ustekinumab, and 5470 for risankizumab. Reports for females were approximately 20% more than males, and patients aged 18-64.9 years reported the highest number of AEs. Interestingly, 50/77 PTs in at least 10 cases were classified as unexpected AEs, such as clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab. There are similarities and differences in the presentation of ustekinumab-related and risankizumab-related AEs in males and females. Conclusions Gender-specific patients should be concerned about the occurrence of appropriate AEs when taking medications for CD. Our study provided evidence for ustekinumab and risankizumab in the treatment of CD. FAERS ustekinumab risankizumab IgG1 monoclonal antibody adverse events Crohn's disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Crohn’s disease(CD) is a chronic infammatory bowel disease(IBD) that can result in progressive bowel damage and disability[1]. CD is a global disease in the 21st century and it’s main symptoms include abdominal pain, diarrhea, fatigue, and weight loss[2]. The treatment principle of CD patients is to induce remission and maintain remission. Medical management for CD includes the categories of steroids, immunomodulators(thiopurines, methotrexate), TNFα antagonists(infliximab, adalimumab, certolizumab), Janus kinase inhibitors(upadacitinib), anti-integrin therapies(vedolizumab), interleukin(IL)-12/IL-23 inhibitors(ustekinumab, risankizumab)[2]. Despite the significance of TNF inhibitors in the treatment of CD, in clinical trials and practice, some patients do not respond to treatment and nearly half of the patients require increased doses after 12 weeks of treatment[3]. Therefore, risankizumab and ustekinumab entered everyone's field of vision. Risankizumab and ustekinumab are both IgG1 monoclonal antibodies. The ustekinumab acts by binding to the p40 subunit shared by proinflammatory IL-23 and IL-12[4]. The studyshowed that for patients with non-response to anti-TNF treatment and immunosuppressive therapy failure or intolerance, ustekinumab group’s clinical remission rate was higher than the placebo group at week 3 and week 8, and the levels of C-reactive protein and fecal calprotectin were significantly improved and continuously decreased at week 3 of ustekinumab treatment[5]. One meta-analysis and systematic review study showed that ustekinumab provided clinical remission and improvement in patients with moderate to severe CD[6]. Two substudiesinvolving 252 patients showed more endoscopic improvements in patients treated with ustekinumab compared with placebo, and the mean histology activity scores decreased at week 8[7,8].Risankizumab acts by binding to the p19 subunit shared by proinflammatory IL-23[4]. Two placebo-controlled randomized controlled trial studiesshowed that patients with moderate to severe active CD, treated with risankizumab were more likely to achieve clinical response and clinical remission compared with placebo[9]. In addition, risankizumab was more likely to achieve endoscopic response and endoscopic remission than placebo[9]. In a subsequent trial of single maintenance therapy, more patients treated with risankizumab achieved clinical remission or endoscopic response compared with placebo[10,11]. Clinical trial data suggest a favorable benefit-to-risk profile for IL-12/IL-23 inhibitors in CD. Researches showed that there was no significant difference between ustekinumab or risankizumab and placebo for AEs, serious adverse events(SAEs), or serious infection events[9,12]. AEs of concern for ustekinumab include infections, headache, nausea, arthralgia, injection site reactions, abdominal pain, pyrexia, nasopharyngitis, and fatigue[5], while AEs of concern for risankizumab include nasopharyngitis, arthralgia, headache, nausea, abdominal pain, diarrhoea, and anaemia[9]. In a head-to-head study[13], risankizumab demonstrated superiority in clinical response at week 24 and endoscopic response at week 48 compared with ustekinumab. In terms of safety, the percentages of patients who experienced any AEs, SAEs, or AEs that led to discontinuation of treatment were similar, and Covid-19 was the most frequently reported AE in both groups[13]. Although the proportion of SAEs was lower with risankizumab than with ustekinumab, the proportion of developed serious infections was similar in both groups[13]. While much has been learned about the efficacy and safety profile of ustekinumab and risankizumab in CD in clinical trials, there is a paucity of studies on comparative real-world safety profiles. The FDA Adverse Event Reporting System (FAERS) is one of the most representative self-reporting databases for AEs monitoring, which can help researchers identify new and potential AEs in the real world[14]. In this study, we evaluated AE reports for ustekinumab and risankizumab, aiming to evaluate potential associations between drugs and AE reports through FAERS data mining. Furthermore, it also aims to compare the AEs of two drugs in the real world and provide references for the clinical safety of drug use. Materials and Methods Data sources and procedures Our study collected ustekinumab’ AEs data from the FAERS Quarterly Data Extract Files between the third quarter of 2016 (FDA marketing approval of ustekinumab for the treatment of CD) and second quarter of 2024, and risankizumab data was collected from the second quarter of 2022 (FDA marketing approval of risankizumab for the treatment of CD) to the second quarter of 2024. Drug identification Reports involving two humanized IgG1 monoclonal antibodies for CD: ustekinumab and risankizumab. During the data mining process, they were identified in the FAERS by brand and generic name. Statistical analysis As shown in Table 1, we assessed the relationship between AEs and humanized IgG1 monoclonal antibodies using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) using the contingency table calculator from Open Vigil. A risk signal was considered when the lower limit of the corresponding 95% CI was >1, a >3, and PRR ≥2 with an associated χ2 value of 4 or more. Table S1 shows the calculation formula. Data were analyzed using MYSQL (version 8.0) and R studio software (version 9.1.0). Table 1 Calculation of reporting odds ratio (ROR) and Proportional Reporting Ratio(PRR) . Items Reports with target AE Reports without target AE Reports with ustekinumab/risankizumab a b Reports without ustekinumab/risankizumab c d Total a+c b+d Abbreviations: a, number of reports containing both the target drug (ustekinumab/risankizumab) and target AE; b, number of reports containing other AEs of the target drug; c, number of reports containing the target AE of other drugs; d, number of reports containing other drugs and other AEs Results Baseline characteristics of ustekinumab and risankizumab The baseline characteristics of AEs related to drug treatment of CD are shown in Table 2. For the treatment of CD, a total of 2,5223 AE reports were retrieved from FAERS, with 1,9753 for ustekinumab (Q3 of 2016-Q2 of 2024), and 5470 for risankizumab (Q2 of 2022-Q2 of 2024). In terms of gender, reports for females were approximately 20% more than males for two drugs. As for age composition, the highest proportion is 18-64.9 years old(48.9% for ustekinumab, 31.7% for risankizumab). What's more, hospitalization was the most common outcome for two drugs(22.2% for ustekinumab, 25.7% for risankizumab). The United States and Canada reported the highest number of AEs. Table 2 Clinical characteristics of reports with ustekinumab and risankizumab from the FAERS database. Characteristic Ustekinumab Risankizumab Overall N=19753 N=5470 Gender Female 11378 57.60% 3107 56.80% Male 6945 35.20% 2102 38.40% Uknown 1430 7.20% 261 4.80% Weight(kg) ＜50 535 2.70% 19 0.30% 50-100 4017 20.30% 390 1.10% ＞100 574 2.90% 59 7.10% Unknown 14627 74.00% 5002 91.40% Age（year） ＜18 513 2.6% 12 0.2% 18～64.9 9664 48.9% 1733 31.7% 65～85 1681 8.5% 608 11.1% >85 51 0.3% 16 0.3% Unknown 7844 39.7% 3101 56.7% Years 2016 104 0.5% / / 2017 962 4.9% / / 2018 2155 10.9% / / 2019 2602 13.2% / / 2020 5254 26.6% / / 2021 2427 12.3% / / 2022 2535 12.8% 598 10.9% 2023 2582 13.1% 2778 50.8% 2024 1123 5.7% 2094 38.3% Occupation of the reporter Customer 8323 42.10% 4529 82.80% Other health-professional 5087 25.80% 478 8.70% Medical Doctor 3041 15.40% 374 6.80% Pharmacists 1600 8.10% 70 1.30% Others 1445 7.30% / / Unknown 256 1.30% 19 0.30% Outcomes unknown 7105 36.0% 2261 41.30% Other serious outcomes 7679 38.9% 1707 31.20% Hospitalization 4377 22.2% 1404 25.70% Death 261 1.3% 74 1.40% Life-threatening 209 1.1% 8 0.10% Disability 74 0.4% 13 0.20% Required intervention 26 0.1% 3 0.10% Congenital Anomaly 22 0.1% 0 0 Country of the reporter United States 10827 54.80% 4525 82.70% Canada 4273 21.60% 782 14.30% others 4653 23.60% 163 3.00% Disproportionality analysis As shown in Table 3, the disproportionality at the system organ class (SOC) level of ustekinumab and risankizumab was observed in the FAERS. Ustekinumab-induced AEs presented eight areas of toxicity with statistically significant RORs and risankizumab-induced AEs presented eleven areas of toxicity. Of the statistically significant areas of toxicity, ustekinumab and risankizumab had five identical areas: nervous system disorders; product issues; surgical and medical procedures; neoplasms benign, malignant and unspecified (incl cysts and polyps); hepatobiliary disorders, respectively. In addition, ustekinumab-induced AEs were statistically significant in three areas: injury, poisoning and procedural complications; infections and infestations; congenital, familial and genetic disorders. Risankizumab-induced AEs were statistically significant in six areas: gastrointestinal disorders; general disorders and administration site conditions; metabolism and nutrition disorders; renal and urinary disorders; cardiac disorders; and ear and labyrinth disorders. There are 129/114 different preferred terms (PTs) of ustekinumab-associated/ risankizumab-associated AEs reported in the FAERS in at least 10 cases. The top 20 PTs of the two drugs are shown in Fig. 1. Table 4 lists the number of PTs in the top 10 for each corresponding SOC, including 69/95 PTs and 18/18 SOCs for ustekinumab/risankizumab, and others are described in Supplementary Table S2. Interestingly, among the 69/95 PTs, 50/77 PTs were classified as unexpected AEs in our data analysis, which were uncovered in the drug label and phase II/III clinical trial, such as clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab. Table 3 Signal strength of AEs of ustekinumab and risankizumab at the system organ class (SOC) level in the FAERS database. (Quantity from high to low) Ustekinumab Risankizumab SOC case number ROR(95%Cl) SOC case number ROR(95%Cl) *injury, poisoning and procedural complications 11544 1.69 ( 1.66 - 1.73 ) *gastrointestinal disorders 3655 1.33 ( 1.28 - 1.38 ) gastrointestinal disorders 8509 0.78 ( 0.76 - 0.8 ) *general disorders and administration site conditions 3132 1.16 ( 1.11 - 1.21 ) *infections and infestations 7583 1.77 ( 1.72 - 1.81 ) infections and infestations 1309 0.91 ( 0.86 - 0.96 ) general disorders and administration site conditions 6579 0.69 ( 0.67 - 0.7 ) *surgical and medical procedures 1179 4.33 ( 4.06 - 4.61 ) *nervous system disorders 2725 1.23 ( 1.18 - 1.28 ) *nervous system disorders 1076 1.81 ( 1.7 - 1.93 ) *product issues 2661 8.14 ( 7.76 - 8.53 ) musculoskeletal and connective tissue disorders 948 0.8 ( 0.75 - 0.85 ) musculoskeletal and connective tissue disorders 2057 0.55 ( 0.52 - 0.57 ) injury, poisoning and procedural complications 907 0.3 ( 0.28 - 0.32 ) *surgical and medical procedures 2041 1.77 ( 1.69 - 1.86 ) investigations 746 0.57 ( 0.53 - 0.62 ) skin and subcutaneous tissue disorders 1810 0.84 ( 0.8 - 0.88 ) skin and subcutaneous tissue disorders 624 0.98 ( 0.9 - 1.06 ) investigations 1632 0.4 ( 0.39 - 0.43 ) respiratory, thoracic and mediastinal disorders 433 0.81 ( 0.73 - 0.89 ) respiratory, thoracic and mediastinal disorders 1251 0.72 ( 0.68 - 0.76 ) psychiatric disorders 306 0.85 ( 0.75 - 0.95 ) *neoplasms benign, malignant and unspecified (incl cysts and polyps) 1012 1.37 ( 1.28 - 1.46 ) *metabolism and nutrition disorders 296 1.33 ( 1.18 - 1.5 ) psychiatric disorders 788 0.62 ( 0.58 - 0.67 ) *neoplasms benign, malignant and unspecified (incl cysts and polyps) 285 1.78 ( 1.57 - 2 ) vascular disorders 634 0.6 ( 0.56 - 0.65 ) *product issues 264 2.39 ( 2.1 - 2.71 ) eye disorders 454 0.65 ( 0.59 - 0.71 ) vascular disorders 262 0.83 ( 0.74 - 0.94 ) metabolism and nutrition disorders 448 0.53 ( 0.48 - 0.58 ) *renal and urinary disorders 201 1.49 ( 1.3 - 1.72 ) renal and urinary disorders 423 0.79 ( 0.72 - 0.88 ) *hepatobiliary disorders 153 1.67 ( 1.41 - 1.96 ) *hepatobiliary disorders 403 1.18 ( 1.07 - 1.31 ) *cardiac disorders 147 1.27 ( 1.08 - 1.5 ) immune system disorders 371 0.85 ( 0.76 - 0.94 ) eye disorders 141 0.66 ( 0.56 - 0.78 ) cardiac disorders 362 0.77 ( 0.7 - 0.86 ) immune system disorders 93 0.78 ( 0.63 - 0.95 ) blood and lymphatic system disorders 274 0.85 ( 0.75 - 0.96 ) blood and lymphatic system disorders 74 1.02 ( 0.81 - 1.29 ) reproductive system and breast disorders 200 0.68 ( 0.59 - 0.79 ) reproductive system and breast disorders 71 0.85 ( 0.67 - 1.08 ) pregnancy, puerperium and perinatal conditions 175 0.85 ( 0.73 - 0.99 ) *ear and labyrinth disorders 70 1.34 ( 1.05 - 1.7 ) ear and labyrinth disorders 121 0.69 ( 0.58 - 0.83 ) social circumstances 46 0.56 ( 0.42 - 0.75 ) social circumstances 121 0.49 ( 0.41 - 0.59 ) pregnancy, puerperium and perinatal conditions 24 0.6 ( 0.4 - 0.89 ) *congenital, familial and genetic disorders 82 1.74 ( 1.38 - 2.18 ) endocrine disorders 18 1.31 ( 0.82 - 2.1 ) endocrine disorders 45 0.76 ( 0.56 - 1.02 ) congenital, familial and genetic disorders 9 0.71 ( 0.37 - 1.38 ) *indicates statistically significant signals in the algorithm. Abbreviations: ROR, reporting odds ratio; CI, confidence interval. Table 4 Signal strength of the preferred term (PT) and the clinical priority assessing results. Drugs Ustekinumab Risankizumab SOC PT case number ROR(95%Cl) PRR(χ2) PT case number ROR(95%Cl) PRR(χ2) injury, poisoning and procedural complications infusion related reaction 511 2.85 ( 2.59 - 3.13 ) 2.83 ( 513.94 ) fall* 99 2.06 ( 1.68 - 2.53 ) 2.05 ( 50.08 ) injection related reaction 29 24.84 ( 13.79 - 44.73 ) 24.83 ( 253.97 ) / / / / exposure via breast milk* 18 3.38 ( 2.03 - 5.64 ) 3.38 ( 24.77 ) / / / / anastomotic stenosis* 11 2.32 ( 1.23 - 4.38 ) 2.32 ( 7.19 ) / / / / skin abrasion* 10 2.03 ( 1.05 - 3.92 ) 2.03 ( 4.6 ) / / / / gastrointestinal disorders / / / / intestinal obstruction* 300 3.94 ( 3.49 - 4.45 ) 3.89 ( 569.96 ) / / / / small intestinal obstruction* 81 4.07 ( 3.22 - 5.14 ) 4.05 ( 163.37 ) / / / / flatulence* 79 2.59 ( 2.06 - 3.27 ) 2.59 ( 70.57 ) / / / / gastrointestinal sounds abnormal* 75 9.07 ( 6.99 - 11.76 ) 9.03 ( 407.67 ) / / / / gastrointestinal haemorrhage* 24 4.47 ( 2.91 - 6.88 ) 4.47 ( 55.9 ) / / / / intestinal perforation* 23 2.91 ( 1.89 - 4.47 ) 2.9 ( 26.09 ) / / / / gastrointestinal obstruction* 23 3.91 ( 2.53 - 6.04 ) 3.9 ( 43.7 ) / / / / gastrointestinal pain 20 2.29 ( 1.45 - 3.62 ) 2.29 ( 13.51 ) / / / / gastrointestinal scarring* 18 4.27 ( 2.6 - 7 ) 4.26 ( 39.16 ) / / / / large intestine perforation* 14 5.43 ( 3.06 - 9.61 ) 5.42 ( 42.48 ) / / / / small intestinal stenosis* 14 2.53 ( 1.46 - 4.36 ) 2.52 ( 11.84 ) infections and infestations pneumonia 575 2.35 ( 2.15 - 2.56 ) 2.33 ( 382.16 ) sepsis 56 3.11 ( 2.36 - 4.09 ) 3.1 ( 71.93 ) lower respiratory tract infection 492 7.35 ( 6.6 - 8.18 ) 7.29 ( 1815.62 ) upper respiratory tract infection 36 3.58 ( 2.53 - 5.06 ) 3.57 ( 59.29 ) clostridium difficile infection* 275 2.7 ( 2.37 - 3.06 ) 2.69 ( 248.54 ) kidney infection 21 2.2 ( 1.41 - 3.43 ) 2.2 ( 12.73 ) anal abscess 200 2.18 ( 1.88 - 2.53 ) 2.18 ( 111.64 ) diverticulitis* 21 2.49 ( 1.59 - 3.89 ) 2.49 ( 17.2 ) cellulitis* 141 2.58 ( 2.16 - 3.08 ) 2.57 ( 116.44 ) postoperative wound infection* 20 3.05 ( 1.92 - 4.84 ) 3.05 ( 24.91 ) kidney infection 133 4.42 ( 3.64 - 5.36 ) 4.41 ( 272.61 ) abdominal abscess* 17 2.18 ( 1.33 - 3.56 ) 2.18 ( 10.04 ) abdominal abscess* 98 2.69 ( 2.17 - 3.34 ) 2.69 ( 88.77 ) appendicitis 14 3.79 ( 2.17 - 6.62 ) 3.79 ( 25.36 ) gastrointestinal infection 84 2.14 ( 1.7 - 2.69 ) 2.14 ( 44.79 ) post procedural infection* 14 2.11 ( 1.23 - 3.64 ) 2.11 ( 7.64 ) tooth abscess* 82 3.71 ( 2.91 - 4.72 ) 3.71 ( 130.63 ) vascular device infection* 11 3.85 ( 2.05 - 7.22 ) 3.85 ( 20.42 ) upper respiratory tract infection 82 2.19 ( 1.74 - 2.76 ) 2.19 ( 46.45 ) bacteraemia 10 5.31 ( 2.7 - 10.43 ) 5.31 ( 29.51 ) general disorders and administration site conditions therapeutic response decreased* 308 7.38 ( 6.44 - 8.46 ) 7.35 ( 1144.71 ) injection site haemorrhage* 127 6.99 ( 5.76 - 8.5 ) 6.95 ( 521.17 ) complication associated with device* 25 3.74 ( 2.42 - 5.79 ) 3.74 ( 40.39 ) unevaluable event* 98 4.47 ( 3.61 - 5.53 ) 4.44 ( 226.87 ) / / / / feeling abnormal* 92 2.6 ( 2.1 - 3.22 ) 2.59 ( 82.76 ) / / / / injection site erythema 56 3.46 ( 2.62 - 4.57 ) 3.45 ( 87.15 ) / / / / injection site papule 45 10.69 ( 7.59 - 15.05 ) 10.66 ( 287.26 ) / / / / obstruction* 45 4.29 ( 3.14 - 5.88 ) 4.29 ( 98.68 ) / / / / hernia* 45 2.7 ( 1.99 - 3.66 ) 2.69 ( 43.83 ) / / / / injection site swelling 43 4.09 ( 2.97 - 5.63 ) 4.08 ( 87.63 ) / / / / injection site reaction 31 4.01 ( 2.75 - 5.84 ) 4 ( 61.31 ) / / / / injection site pruritus 22 2.03 ( 1.32 - 3.13 ) 2.03 ( 10.71 ) / / / / injection site mass 22 9.57 ( 5.9 - 15.5 ) 9.56 ( 126.41 ) nervous system disorders cerebrovascular accident 103 2.09 ( 1.7 - 2.57 ) 2.09 ( 51.31 ) loss of consciousness* 78 4.52 ( 3.56 - 5.75 ) 4.51 ( 184.2 ) transient ischaemic attack* 33 2.4 ( 1.66 - 3.46 ) 2.4 ( 23.29 ) cerebrovascular accident* 53 4.13 ( 3.09 - 5.51 ) 4.12 ( 109.47 ) multiple sclerosis* 26 2.21 ( 1.47 - 3.34 ) 2.21 ( 15.13 ) seizure* 43 4.41 ( 3.2 - 6.08 ) 4.4 ( 98.07 ) facial paralysis* 25 4.01 ( 2.58 - 6.23 ) 4.01 ( 44.87 ) presyncope* 18 3.88 ( 2.37 - 6.35 ) 3.88 ( 33.9 ) posterior reversible encephalopathy syndrome* 23 13.13 ( 7.53 - 22.9 ) 13.13 ( 139.14 ) lethargy* 15 2.04 ( 1.21 - 3.44 ) 2.04 ( 7.41 ) cerebral haemorrhage 14 2.63 ( 1.49 - 4.64 ) 2.63 ( 12.09 ) balance disorder* 14 2.08 ( 1.21 - 3.58 ) 2.08 ( 7.32 ) sensory disturbance* 13 2.71 ( 1.5 - 4.88 ) 2.71 ( 11.9 ) hypersomnia* 13 3.59 ( 2.01 - 6.38 ) 3.58 ( 21.52 ) idiopathic intracranial hypertension* 11 8.07 ( 3.89 - 16.74 ) 8.07 ( 44.72 ) transient ischaemic attack* 12 3.82 ( 2.09 - 6.99 ) 3.82 ( 22.07 ) ischaemic stroke* 11 2.65 ( 1.4 - 5.02 ) 2.65 ( 9.63 ) multiple sclerosis* 12 5.46 ( 2.95 - 10.13 ) 5.46 ( 36.73 ) / / / / head discomfort* 10 2.43 ( 1.27 - 4.64 ) 2.43 ( 7.75 ) *product issues syringe issue* 588 208.15 ( 153.21 - 282.8 ) 205.92 ( 8353.85 ) device issue* 217 8.03 ( 6.9 - 9.34 ) 7.93 ( 1032.09 ) needle issue* 547 36.69 ( 31.46 - 42.79 ) 36.33 ( 5602 ) product quality issue* 12 3.96 ( 2.16 - 7.24 ) 3.95 ( 23.28 ) device issue* 336 1.72 ( 1.54 - 1.93 ) 1.72 ( 90.56 ) / / / / device deployment issue* 177 248.75 ( 135.28 - 457.4 ) 247.94 ( 2547.65 ) / / / / device malfunction* 146 17.62 ( 13.9 - 22.34 ) 17.58 ( 1066.54 ) / / / / device defective* 116 35.12 ( 25.26 - 48.82 ) 35.05 ( 1171.95 ) / / / / product leakage* 99 49.3 ( 32.93 - 73.8 ) 49.21 ( 1115.14 ) / / / / drug delivery system malfunction* 80 49.38 ( 31.51 - 77.38 ) 49.31 ( 901.6 ) / / / / liquid product physical issue* 78 15.63 ( 11.41 - 21.42 ) 15.61 ( 529.9 ) / / / / product packaging issue* 67 43.07 ( 27.02 - 68.66 ) 43.02 ( 725.26 ) / / / / surgical and medical procedures intestinal resection 419 3.38 ( 3.04 - 3.76 ) 3.36 ( 571.46 ) surgery* 199 9.74 ( 8.29 - 11.45 ) 9.64 ( 1154.57 ) surgery 269 2.63 ( 2.31 - 2.99 ) 2.62 ( 230.48 ) intestinal resection* 97 4.69 ( 3.78 - 5.81 ) 4.67 ( 240.57 ) colectomy 141 2.25 ( 1.89 - 2.69 ) 2.25 ( 85.46 ) colectomy* 84 7.58 ( 5.96 - 9.65 ) 7.55 ( 378.03 ) therapy cessation* 70 3.77 ( 2.91 - 4.9 ) 3.77 ( 114.57 ) ileostomy* 59 4.86 ( 3.69 - 6.41 ) 4.85 ( 154.18 ) small intestinal resection* 58 2.44 ( 1.85 - 3.22 ) 2.44 ( 42.64 ) hospitalisation* 55 2.13 ( 1.62 - 2.8 ) 2.13 ( 30.65 ) intestinal operation* 52 2.65 ( 1.98 - 3.56 ) 2.65 ( 45.71 ) ostomy bag placement* 37 18.01 ( 11.94 - 27.18 ) 17.98 ( 364.64 ) ileectomy* 25 2.88 ( 1.88 - 4.41 ) 2.87 ( 25.76 ) stoma creation* 34 8.07 ( 5.51 - 11.81 ) 8.05 ( 164.05 ) caesarean section* 22 2.09 ( 1.34 - 3.27 ) 2.09 ( 11.05 ) small intestinal resection* 34 7.13 ( 4.89 - 10.38 ) 7.11 ( 143.18 ) colectomy total* 21 4 ( 2.47 - 6.46 ) 3.99 ( 37.45 ) colostomy* 25 4.82 ( 3.15 - 7.36 ) 4.81 ( 64.62 ) proctectomy* 17 3.01 ( 1.79 - 5.06 ) 3.01 ( 19.1 ) intestinal operation* 24 4.33 ( 2.82 - 6.66 ) 4.33 ( 53.36 ) skin and subcutaneous tissue disorders skin reaction 20 2.14 ( 1.34 - 3.42 ) 2.14 ( 10.67 ) hyperhidrosis* 45 2.53 ( 1.87 - 3.44 ) 2.53 ( 38.28 ) / / / / rash papular 13 2.85 ( 1.61 - 5.03 ) 2.84 ( 14.15 ) investigations liver function test abnormal* 23 3.17 ( 2.02 - 4.96 ) 3.16 ( 28.25 ) haemoglobin decreased 36 2.12 ( 1.51 - 2.98 ) 2.12 ( 19.83 ) general physical condition abnormal* 12 2.43 ( 1.32 - 4.47 ) 2.43 ( 8.75 ) sars-cov-2 test positive 25 2.51 ( 1.67 - 3.78 ) 2.51 ( 20.81 ) / / / / blood potassium decreased* 23 3.59 ( 2.32 - 5.53 ) 3.58 ( 38.09 ) / / / / white blood cell count increased* 19 2.04 ( 1.28 - 3.25 ) 2.04 ( 9.41 ) / / / / full blood count decreased* 15 13.04 ( 7.08 - 24.01 ) 13.03 ( 114.55 ) / / / / blood magnesium decreased* 14 3.4 ( 1.96 - 5.92 ) 3.4 ( 21.22 ) / / / / inflammatory marker increased* 14 3.09 ( 1.78 - 5.36 ) 3.09 ( 17.84 ) / / / / blood glucose increased* 13 3.24 ( 1.83 - 5.75 ) 3.24 ( 18.1 ) / / / / alanine aminotransferase increased 13 2.54 ( 1.44 - 4.47 ) 2.54 ( 11.11 ) / / / / white blood cell count decreased* 11 2.5 ( 1.35 - 4.64 ) 2.5 ( 9.13 ) respiratory, thoracic and mediastinal disorders pharyngeal swelling 19 2.82 ( 1.73 - 4.59 ) 2.82 ( 18.8 ) pulmonary embolism* 28 3.1 ( 2.1 - 4.58 ) 3.1 ( 35.94 ) interstitial lung disease* 17 2.3 ( 1.38 - 3.83 ) 2.3 ( 10.85 ) pulmonary thrombosis* 21 15.07 ( 8.88 - 25.56 ) 15.05 ( 180.63 ) pneumonitis 15 2.14 ( 1.25 - 3.67 ) 2.14 ( 8 ) throat tightness* 14 2.28 ( 1.32 - 3.93 ) 2.28 ( 9.32 ) dry throat 11 2.12 ( 1.13 - 3.98 ) 2.12 ( 5.71 ) pneumothorax* 11 5.01 ( 2.64 - 9.5 ) 5.01 ( 30.02 ) neoplasms benign, malignant and unspecified (incl cysts and polyps) breast cancer* 57 2.49 ( 1.88 - 3.29 ) 2.49 ( 43.7 ) neoplasm malignant* 24 2.27 ( 1.5 - 3.44 ) 2.27 ( 15.82 ) squamous cell carcinoma 35 2.18 ( 1.53 - 3.1 ) 2.17 ( 19.47 ) breast cancer female* 14 4.51 ( 2.57 - 7.93 ) 4.51 ( 33.04 ) gastrointestinal carcinoma* 20 2.14 ( 1.34 - 3.42 ) 2.14 ( 10.67 ) malignant melanoma* 12 2.48 ( 1.37 - 4.47 ) 2.47 ( 9.71 ) pancreatic carcinoma* 14 3.22 ( 1.81 - 5.73 ) 3.22 ( 17.72 ) colon cancer* 11 3.85 ( 2.05 - 7.22 ) 3.85 ( 20.42 ) hepatic cancer* 13 2.36 ( 1.31 - 4.23 ) 2.36 ( 8.81 ) lung neoplasm malignant 10 2.37 ( 1.24 - 4.52 ) 2.37 ( 7.31 ) anal cancer* 10 2.49 ( 1.27 - 4.85 ) 2.49 ( 7.64 ) / / / / psychiatric disorders mood swings* 15 2.34 ( 1.36 - 4.02 ) 2.33 ( 9.94 ) insomnia* 88 2.16 ( 1.74 - 2.68 ) 2.15 ( 50.52 ) / / / / suicidal ideation* 11 2.72 ( 1.47 - 5.05 ) 2.72 ( 10.92 ) vascular disorders / / / / hypotension* 42 2.18 ( 1.59 - 2.98 ) 2.18 ( 24.87 ) / / / / thrombosis* 35 2.96 ( 2.09 - 4.2 ) 2.96 ( 41.19 ) / / / / internal haemorrhage* 12 4.99 ( 2.7 - 9.21 ) 4.99 ( 32.57 ) metabolism and nutrition disorders / / / / dehydration* 89 2.82 ( 2.26 - 3.5 ) 2.81 ( 94.46 ) / / / / hypophagia* 25 3.62 ( 2.39 - 5.49 ) 3.62 ( 42.1 ) renal and urinary disorders iga nephropathy* 15 2.34 ( 1.36 - 4.02 ) 2.33 ( 9.94 ) renal failure* 21 3.26 ( 2.07 - 5.12 ) 3.25 ( 29.46 ) / / / / dysuria* 14 2.28 ( 1.32 - 3.93 ) 2.28 ( 9.32 ) / / / / chromaturia* 13 6.21 ( 3.41 - 11.32 ) 6.21 ( 46.72 ) hepatobiliary disorders cholelithiasis* 75 2.03 ( 1.6 - 2.59 ) 2.03 ( 34.71 ) hepatic cirrhosis 26 2.39 ( 1.6 - 3.57 ) 2.39 ( 19.39 ) cholecystitis* 16 2.65 ( 1.56 - 4.51 ) 2.65 ( 14.04 ) cholelithiasis* 18 2.09 ( 1.29 - 3.37 ) 2.09 ( 9.53 ) hepatic function abnormal* 15 4.06 ( 2.3 - 7.16 ) 4.05 ( 27.33 ) hepatic steatosis* 15 2.99 ( 1.76 - 5.09 ) 2.99 ( 17.95 ) / / / / gallbladder disorder* 13 2.94 ( 1.66 - 5.2 ) 2.93 ( 15.04 ) immune system disorders anaphylactic reaction 81 2.68 ( 2.12 - 3.39 ) 2.68 ( 72.62 ) / / / / cardiac disorders / / / / myocardial infarction* 24 2.92 ( 1.92 - 4.44 ) 2.92 ( 27.42 ) / / / / cardiac disorder* 19 2.06 ( 1.29 - 3.28 ) 2.06 ( 9.61 ) / / / / atrial fibrillation* 17 2.32 ( 1.42 - 3.81 ) 2.32 ( 11.82 ) / / / / cardiac failure congestive* 14 6.18 ( 3.47 - 11.01 ) 6.17 ( 49.95 ) blood and lymphatic system disorders thrombocytopenia* 23 2.19 ( 1.41 - 3.39 ) 2.19 ( 12.99 ) / / / / reproductive system and breast disorders erectile dysfunction* 10 3.02 ( 1.53 - 5.95 ) 3.02 ( 11.31 ) / / / / pregnancy, puerperium and perinatal conditions premature labour* 11 2.87 ( 1.51 - 5.47 ) 2.87 ( 11.32 ) / / / / ear and labyrinth disorders / / / / hypoacusis* 13 2.63 ( 1.49 - 4.63 ) 2.62 ( 11.98 ) social circumstances insurance issue* 27 2.21 ( 1.48 - 3.31 ) 2.21 ( 15.7 ) / / / / *PTs uncovered by drug package insert and phase II/III clinical trials Time-to-onset analysis The time from ustekinumab or risankizumab use to AEs occurrence was assessed and shown in Fig. 2. The median time to the ustekinumab-related onset of AEs was 195 days (IQR 56 - 505.5 days), and ＞360 days, 181-360 days, and 0-30 days after medication accounted for 33.1% and 18.9%, 16.2% respectively. The median time to the risankizumab-related onset of AEs was 105 days (IQR 42.25 - 214 days), 181-360 days and 0-30 days after medication accounted for 24.4% and 19.3%. Gender subgroup analysis As shown in Table 5, there are similarities and differences in the presentation of ustekinumab-related and risankizumab-related AEs in males and females. Negative signals are detailed in Supplementary Table S3. Table 5 Positive SOC signal in patients of different genders. Gender Female Male Drug SOC case number ROR(95%Cl) SOC case number ROR(95%Cl) Ustekinumab injury, poisoning and procedural complications 6774 2.01 ( 1.95 - 2.06 ) injury, poisoning and procedural complications 4073 1.96 ( 1.89 - 2.03 ) infections and infestations 4561 1.76 ( 1.71 - 1.82 ) infections and infestations 2427 1.78 ( 1.7 - 1.86 ) nervous system disorders 1738 1.21 ( 1.15 - 1.28 ) product issues 945 6.15 ( 5.69 - 6.65 ) product issues 1489 6.91 ( 6.48 - 7.37 ) nervous system disorders 830 1.15 ( 1.07 - 1.24 ) surgical and medical procedures 1171 1.58 ( 1.49 - 1.68 ) surgical and medical procedures 721 1.53 ( 1.41 - 1.65 ) neoplasms benign, malignant and unspecified (incl cysts and polyps)* 523 1.21 ( 1.1 - 1.32 ) pregnancy, puerperium and perinatal conditions* 18 2.23 ( 1.35 - 3.67 ) Risankizumab gastrointestinal disorders* 2181 1.15 ( 1.1 - 1.21 ) general disorders and administration site conditions 1145 1.12 ( 1.05 - 1.2 ) general disorders and administration site conditions 1890 1.17 ( 1.12 - 1.24 ) surgical and medical procedures 470 3.64 ( 3.28 - 4.03 ) surgical and medical procedures 690 3.93 ( 3.62 - 4.28 ) nervous system disorders 411 1.94 ( 1.75 - 2.16 ) nervous system disorders 639 1.64 ( 1.51 - 1.79 ) neoplasms benign, malignant and unspecified (incl cysts and polyps) 124 1.35 ( 1.12 - 1.62 ) metabolism and nutrition disorders 177 1.18 ( 1.01 - 1.37 ) product issues 119 1.81 ( 1.49 - 2.18 ) neoplasms benign, malignant and unspecified (incl cysts and polyps) 154 1.59 ( 1.34 - 1.87 ) metabolism and nutrition disorders 118 1.35 ( 1.11 - 1.63 ) product issues 144 1.81 ( 1.52 - 2.15 ) hepatobiliary disorders 72 1.75 ( 1.37 - 2.24 ) renal and urinary disorders* 111 1.6 ( 1.32 - 1.94 ) cardiac disorders* 68 1.3 ( 1.01 - 1.67 ) hepatobiliary disorders 79 1.28 ( 1.02 - 1.6 ) / / / ear and labyrinth disorders* 50 1.6 ( 1.2 - 2.14 ) / / / *Different positive SOC signals in patients of different genders For ustekinumab, female-induced AEs were statistically significant in neoplasms benign, malignant and unspecified (incl cysts and polyps) (n=523, ROR=1.21, 95% CI=1.10-1.32). In contrast, male-induced AEs were statistically significant in pregnancy, puerperium and perinatal conditions(n=18, ROR=2.23, 95% CI=1.35-3.67). For risankizumab, female-induced AEs were statistically significant in gastrointestinal disorders(n=2181, ROR 1.15, 95% CI: 1.10 - 1.21), renal and urinary disorders(n=111, ROR 1.60, 95% CI: 1.32 - 1.94), and ear and labyrinth disorders(n=50, ROR 1.60, 95% CI:1.20 - 2.14 ), while male-induced AEs were statistically significant in cardiac disorders(n=68, ROR 1.30, 95% CI:1.01-1.67). We compared PTs induced by ustekinumab/risankizumab in different gender groups, the top 10 PTs in each subgroup are shown in Fig. 3, and others are detailed in Supplementary Table S4. The PTs of females were different from males when taking ustekinumab: exposure during pregnancy(n=291, ROR 3.20, 95% CI: 2.81 - 3.64), clostridium difficile infection(n=149, ROR 2.26, 95% CI: 1.90 - 2.29). Simultaneously, The different PTs of males were: surgery(n=111, ROR 2.37, 95% CI: 1.94 - 2.91), anal abscess(n=94, ROR 2.36, 95% CI: 1.89 - 2.94). As for risankizumab, PTs of females were: urinary tract infection(n=71, ROR 2.14, 95% CI: 1.68 - 2.74); intestinal resection(n=62, ROR 5.13, 95% CI: 3.89 - 6.78); dehydration(n=59, ROR 2.87, 95% CI: 2.19 - 3.77); feeling abnormal(n=57, ROR 2.77, 95% CI: 2.10 - 3.65); small intestinal obstruction(n=55, ROR 4.27, 95% CI: 3.19 - 5.71); loss of consciousness(n=49, ROR 5.00, 95% CI: 3.66 - 6.82). In contrast, PTs of males were: dizziness(n=72, ROR 2.67, 95% CI: 2.08 - 3.42); fall(n=40, ROR 2.06, 95% CI: 1.48 - 2.86); colectomy(n=39, ROR 7.14, 95% CI: 4.92 - 10.38); insomnia(n=36, ROR 2.56, 95% CI: 1.80 - 3.64); gastrointestinal disorder(n=34, ROR 2.01, 95% CI: 1.41 - 2.88); flatulence(n=34, ROR 2.01, 95% CI: 1.41 - 2.87). We also compared the occurrence of AEs induced by ustekinumab/risankizumab in different sex groups, and the results showed that the median time to the ustekinumab-female group, ustekinumab-male group, ustekinumab-female group, risankizumab-female group, risankizumab-male group, onset of AEs was 155.5 days (IQR 50 - 379 days), 200 days (IQR 55 - 491 days), 103 days (IQR 42 - 214 days), 110 days (IQR 44 - 218.5 days), respectively, as shown in Fig. 4. Discussion The results of this study showed that there were commonalities and significant differences between ustekinumab and risankizumab in reported AEs. Both sets of data showed that the patients were predominantly female, which may be related to the high incidence of CD in girls and women[15]. Furthermore, the proportion of 18-64.9 years was the highest in both sets of data, consistent with research findings[16,17], which may be related to the age distribution of CD onset[16]. The age distribution may be related to the fact that CD was a chronic disease that can only be induced and maintained in remission with treat-to-target, not cured, and patients at every age may report AEs. SAEs in both groups were mainly leading to hospitalization. In this study, 69 signals involving 18 SOC of ustekinumab were mined, including injury, poisoning and procedural complications, gastrointestinal disorders, infections and infestations, general disorders and administration site conditions, nervous system disorders, product issues, surgical and medical procedures, skin and subcutaneous tissue disorders, investigations, respiratory, thoracic and mediastinal disorders, neoplasms benign, malignant and unspecified (incl cysts and polyps), etc. While 95 signals involving 18 SOC of risankizumab were mined, including gastrointestinal disorders, general disorders and administration site conditions, infections and infestations, surgical and medical procedures, nervous system disorders, musculoskeletal and connective tissue disorders, injury, poisoning and procedural complications, investigations, skin and subcutaneous tissue disorders, respiratory, thoracic and mediastinal disorders, psychiatric disorders, etc. For ustekinumab, high-frequency SOCs were primarily observed in reactions such as injury, poisoning and procedural complications, infections and infestations, general disorders and administration site conditions, and nervous system disorders, basically consistent with the results of phase III clinical trials[5]. The injury, poisoning and procedural complications systems with a higher frequency of occurrence in these systems include infusion-related reaction, injection-related reaction, and exposure via breast milk; infections and infestations include pneumonia, lower respiratory tract infection, and clostridium difficile infection; cerebrovascular accident, transient ischaemic attack, and multiple sclerosis have a higher frequency of occurrence in nervous system disorders. These AEs are commonly reported in clinical studies and package inserts[5,13,18,19]. Infusion-related reaction was the most common AE in the injury, poisoning and procedural complications system, consistent with previous research[5,13]. Infusion-related AEs caused by ustekinumab have been reported in some cases[20,21]. Infusion-related reactions, injection-related reactions, therapeutic response decreased, and incomplete dose administration that were not included in the package insert, and clinical trial studies as causally associated with ustekinumab use were found to be related to complex dosing procedures, wrong administration procedures, or technical problems with the device. These findings suggest that by improving the device and optimizing the dosing schedule, some of these AEs can be avoided and the efficacy and safety of ustekinumab can be improved. Pneumonia, and lower respiratory tract infection were the most common AE in the infections and infestations system, consistent with previous research[5,13,17,18,22]. In addition, clinical studies have identified upper respiratory tract inflammation, anal abscess, kidney infection, kidney infection, gastrointestinal infection, etc. caused by ustekinumab, consistent with our findings, and can cause serious infections [ 5,13,22-25] . Therefore, we should pay attention to infection-related symptoms, signs and examination indicators in the process of medication, and use antibiotics promptly. Central nervous system AEs caused by ustekinumab have been reported in the literature [5] , cerebrovascular accident was the most common AE in the nervous system disorders, it has been reported in the literature[5,26-27]. Therefore, we should pay close attention to related symptoms during medication. Risankizumab’s SOC was primarily observed in gastrointestinal disorders, general disorders and administration site conditions, and surgical and medical procedures, consistent with the results of phase III clinical trials[9]. The gastrointestinal disorders systems with a higher frequency of occurrence in these systems include intestinal obstruction, small intestinal obstruction, and flatulence; general disorders and administration site conditions include injection site haemorrhage, injection site erythema, injection site papule, and injection site swelling; surgery, intestinal resection, and colectomy have a higher frequency of occurrence in surgical and medical procedures. These AEs are commonly reported in clinical studies and package inserts[9,13,18]. Clinical trials have shown that in addition to being caused by drugs, AEs of gastrointestinal disorders may also be related to the aggravation of clinical manifestations of CD[9]. Infusion-related AEs caused by risankizumab have been extensively reported in the literature[9,13,17], which should be paid attention to, and pretreatment should be done before use if necessary. Surgery, intestinal resection, and colectomy were closely associated with CD progression requiring surgery[2]. According to the disproportionality analysis, many organs or tissues were involved, although some AEs were reported more frequently than others. As shown in Figure 2, significant AEs of ustekinumab mainly included syringe issues, pneumonia, needle issue, infusion-related reactions, lower respiratory tract infection, and intestinal resection. ‌‌ However , only lower respiratory tract infection and infusion-related reactions were reported in the package insert and clinical trial studies[5,13]. Significant AEs of risankizumab mainly included intestinal obstruction, device issue, surgery, injection site haemorrhage, fall, and unevaluable event. ‌ ‌ W hereas , only injection site haemorrhage was not reported in the package insert and clinical trial studies[28]. In addition, we identified many new PTs for ustekinumab and risankizumab, therefore, we should pay attention not only to the package insert AEs, but also to the AEs that are not recorded. Moreover‌, the common SOC and PT signals of the two drugs were not completely consistent, and we can choose personalized medication according to the different organ function states of the patient to ensure safety. The disproportionation signals were found to be biologically plausible, based on preclinical or clinical studies providing pharmacological evidence. The study found similarities and differences in PTs between the two drugs. In terms of infections and infestations, ustekinumab had a higher incidence than risankizumab. In addition, PT signals of ustekinumab were identified between different infections such as pneumonia, lower respiratory tract infection, clostridium difficile infection, anal abscess, cellulitis, and tooth abscess, whereas none of these signals were seen with risankizumab. Although speculative, this might suggest that ustekinumab——as a “Dual targeting Inhibitors”, may lead to an increased risk of infection[18,29,30]. Theoretically, the use of any immunosuppressant in the treatment of inflammatory disease may lead to impaired host immune function against pathogens. IL-12 and IL-23 influenced the response of T H 1 cells and T H 17 cells respectively to increase the risk of infection[18]. Emerging data from human loss-of-function variants and preclinical studies in mice suggest the relative risk of infection associated with targeting IL-12 and/or IL-23[18]. Therefore, more attention should be paid to secondary infection during the use of ustekinumab. The results of the disproportionality analysis study showed that risankizumab and ustekinumab were associated with a clear cerebrovascular accident signal, which was consistent with our findings[17,31]. Interestingly, the cerebrovascular accident signal of these two drugs was not reported in the package insert. For example, PTs such as cerebrovascular accident, transient ischaemic attack, etc., were seen in the ustekinumab, and PTs such as cerebrovascular accident, transient ischaemic attack, etc., were found in the risankizumab. In addition, in risankizumab, falls, presyncope, loss of consciousness, and balance disorder may also be directly related to cerebrovascular accidents. Although theories have been proposed, the clear biologically plausible mechanisms by which risankizumab and/or IL-23 inhibition affect the risk of cerebrovascular accident have not been elucidated in the literature. Some animal studies have shown that IL-23 inhibition does not have a protective effect on atherosclerotic plaque formation[32,33]. Inhibition of IL-23 can also inhibit the production of IL-17 by T cells[34]. IL-17 has been found to significantly limit the development of atherosclerotic lesions, and increased levels of IL-17A were associated with the stability of atherosclerotic plaques, and low serum IL-17 levels were further associated with an increased risk of death and recurrent major adverse cardiac events[35,36]. Thus, in theory, lower circulating IL-17 levels after IL-23 inhibition could contribute to atherosclerotic plaque formation and/or destabilization, thereby contributing to cerebrovascular accidents[31]. Although further studies are needed to identify clear mechanisms by which IL-23 inhibition causes or promotes cerebrovascular accidents, close attention should be paid to cerebrovascular accidents during the use of ustekinumab or risankizumab. Malignant disproportionality signals were identified for both drugs. Preclinical animal studies have shown that IL-12 and IL-23 can inhibit tumor growth[37]. Moreover, Malignancies have been reported for ustekinumab and risankizumab in both clinical trials and postmarketing studies for the treatment of CD[10,38,39]. Numerous studies have shown that inhibiting IL-12 may lead to tumor growth. In mouse tests, antigen-presenting cells produce IL-12, and its downstream mediators are critical for anti-tumor immunity[18]. IL-12p35-deficient mice had a higher susceptibility to carcinogens-induced skin papilloma formation than wild-type mice, and tumor incidence and tumor growth were higher in IL-12/23p40-deficient mice than in wild-type controls[18]. The role of IL-23 may be more complex, and its role in tumors still needs to be further studied. IL-23 may have a tumor-suppressive effect on UV-radiation-induced skin-active cancer in mouse models[40]. The IL-12-IL-23 axis plays an important role in controlling the equilibrium phase of cancer immunoediting[41], which is best characterized in a methylcholanthrene-A-induced mouse fibrosarcoma model[42]. The gastrointestinal system that we only found in risankizumab such as iintestinal obstruction, small intestinal obstruction, flatulence, and gastrointestinal sounds abnormal have been identified in this study. Head-to-head studiesin patients with moderate-to-severe CD have shown higher SAEs rates with risankizumab compared with ustekinumab, attributed to SAEs in the gastrointestinal disorders system organ class[13]. Both our statistical findings and clinical trials suggest that gastrointestinal disorders are characteristic AEs of risankizumab[13]. These AEs may be attributed to a higher affinity of risankizumab for IL-23 and an increased potency for its inhibition[43]. A large number of studieshave confirmed the role of IL-23 in mucosal homeostasis[4,44,45], but the functional role of IL-12 in the healthy gut remains unclear, which may support the concept that IL-12 is not necessary to maintain homeostatic conditions in the gut[46,47]. Disproportionality and high-frequency signals involving the product issues that we only found in ustekinumab such as syringe issues, needle issues, device deployment issues, device malfunction, device defective, and product leakage have been identified in this study. This further confirmed the complexity of the ustekinumab delivery device, and the need for improved delivery devices. The infusion-related reaction we only found in ustekinumab, to reduce this AEs, risankizumab may be a better choice, or pretreatment before administration. Unexpected and significant safety signals of ustekinumab, such as investigations, psychiatric disorders, renal and urinary disorders, hepatobiliary disorders, blood and lymphatic system disorders, were detected in our analysis. For risankizumab, unexpected and significant safety signals, such as investigations, psychiatric disorders, vascular disorders, metabolism and nutrition disorders, renal and urinary disorders, hepatobiliary disorders, cardiac disorders, were detected in our analysis. However, these AEs are not explicitly mentioned in the ustekinumab or risankizumab package insert. Unexpected and significant safety PT signals involved in ustekinumab, in order of the number of cases, are cholelithiasis, liver function test abnormal, thrombocytopenia, cholecystitis, iga nephropathy, mood swings. Liver function abnormal[13,48], thrombocytopenia[49-50], and iga nephropathy[51], have been reported in the literature. There is currently no data on ustekinumab-related liver damage in IBD patients. Only a retrospective study analyzing the effects of ustekinumab on 44 patients with psoriasis showed only a mild elevation of aminotransferase in 6 cases[48]. However, experience with its use was limited, therefore, further studies are needed to confirm these data. Elevated levels of IL-23 and IL-17 have been demonstrated in immune thrombocytopenia[52]. However, the mechanism of action of IL-23/IL-17 in normal platelet homeostasis remains unclear. Iga nephropathy was typically characterized by a higher proportion of circulating Th2 rather than Th1[53]. Studies have shown that Th2-associated IL-4 amplifies the formation of Gd-IgA1 by altering the terminal glycosylation that secretes diga1[54]. Thus, it may be that the administration of ustekinumab optimized the immune abnormality of Th1 dominance, leading to a state of Th-2 comparative dominance. This ustekinumab pharmacologically induced mutation of T cell subsets may induce crescent-shaped IgAN by amplifying the formation of Gd-IgA1. Unexpected and significant safety PT signals involved in risankizumab, in order of the number of cases, are dehydration, insomnia, hypotension, haemoglobin decreased, thrombosis, SARS-CoV-2 test positive, and blood potassium decreased. Thrombosis[55], and SARS-CoV-2 test positive[13], have been reported in the literature. SARS-CoV-2 positivity is associated with the background of COVID-19 and suppressed immune function[18]. The AEs of dehydration, insomnia, hypotension, haemoglobin decreased, and blood potassium decreased have not been reported in the literature, and the mechanism remains to be further studied. Dehydration was the high-frequency PT signal observed in risankizumab, so hydration during risankizumab administration is recommended to prevent dehydration. Thrombosis may be associated with the inhibition of IL-23 by risankizumab and may be associated with atherosclerotic plaque formation and/or destabilization[17,35,36]. Therefore, the newly emerging signals of ustekinumab, particularly cholelithiasis, liver function test abnormal, and thrombocytopenia, need to be given a great deal of attention. While the newly emerging signals of risankizumab, particularly dehydration, insomnia, and haemoglobin decreased, need to be given a great deal of attention. We can choose these two drugs individually according to the different organ function status and laboratory examination indicators of patients. For example, when patients have low hemoglobin or potassium levels, ustekinumab is preferred over risankizumab. And risankizumab may be a better choice if the patient has hepatobiliary disease. A statistical analysis of the timeline for AEs was conducted for both drugs, the results showed that the median time to occurrence of AEs after initial treatment with ustekinumab and risankizumab was 195 days and 105 days, respectively, basically consistent with the literature report[17].Only approximately 30% of AEs occurred within 60 days with both drugs, which makes it important to pay attention to AEs that occur during the whole course of medication. We performed a subgroup analysis of sex to examine similarities and differences in AE between the two drugs in gender-specific populations. Patients of different genders have different physiological conditions, and they respond to drugs also differently. Studies showed that male sex was an independent factor in the increased dose demand for ustekinumab for IBD, and gender significantly influenced ustekinumab disposition[56,57]. Therefore, there may be differences in AEs between genders. In ustekinumab, we only found a statistically significant signal of neoplasms benign, malignant and unspecified in females, so when women were treated with ustekinumab for CD, more attention should be paid to AEs related to neoplasms benign, malignant and unspecified. No studies have been found to report this gender difference, and further studies are needed. In ustekinumab, we also only found a statistically significant signal of pregnancy, puerperium and perinatal conditions in males. The drug insert states that no effect on fertility was observed in male cynomolgus monkeys administered with high doses of ustekinumab twice a week prior to and during the mating period. And study showed thatsemen quality and sperm DNA integrity were not affected after male patients were treated with ustekinumab[58], so men who wish to have children can continue using ustekinumab, however, the study objects were small, and the package insert only contain male animal data. Conversely, Our study was a real-world clinical safety study, has a large amount of data, and the number of male patients using ustekinumab is as high as 6945, including multiple species and multiple countries, which has clinical significance, but the specific mechanism has not been reported, and further research is needed. Combined with the results of this study, we believe that men should pay attention to contraception during the use of ustekinumab. According to the results of this study, during the use of risankizumab, women should pay attention to gastrointestinal disorders, renal and urinary disorders, and ear and labyrinth disorders, while men should be concerned about cardiac disorders. For risankizumab, no gender differences in AEs were reported, and further research is needed. We also compared PTs induced by ustekinumab/risankizumab in different gender groups. As can be seen from Figure 4, whether it's the ustekinumab-female subgroup or the ustekinumab-male subgroup, the top PTs were pneumonia, lower respiratory tract infection, syringe issue, infusion-related reaction, and needle issue. Therefore, no matter whether men or women use ustekinumab, they should be concerned about these AEs. In the same way, men and women should be concerned about intestinal obstruction, surgery, device issue, and injection site haemorrhage. Among the female group of two drugs ranked the top 10 PTs, exposure during pregnancy was only found in the ustekinumab-female group, so we should pay more attention to the use of ustekinumab in women during pregnancy. The use of IBD drugs during pregnancy was usually done when it is considered that the benefits outweigh the potential risks of AEs, teratogenicity, and fetal toxicity. Studies have shown that the use of immunomodulators was not associated with the occurrence of pregnancy and birth abnormalities[59]. As mentioned in the package insert, no effects on the fertility of female mice were observed with high doses of IL-12/IL-23p40 antibody prior to and during early pregnancy. However, biologics agents were transferred through the placenta into the neonatal blood in the third trimester (after 30 weeks), some reports recommend that biologics should be avoided in the third trimester, the reason was that the effects of ustekinumab present in the neonatal blood on the development of the neonatal immune system have not been fully elucidated[59,60]. In addition, if ustekinumab was used in the third trimester, the question of whether the newborn will be vaccinated after birth was also a major concern[61]. In a case report of CD treated with ustekinumab until the third trimester, ustekinumab was detected in both maternal blood and umbilical cord blood but was not detected in a 6-month-old infant[60]. However, there were few case studies and literature reports on the effects of ustekinumab on the fetus, and further studies are needed. In the ustekinumab group, the number of female patients with urinary tract infections was higher, which may be related to the high incidence of female urinary tract infections[62]. As for risankizumab, loss of consciousness in female patients, and dizziness, and fall in male patients may be related to central nervous system or cardiovascular AEs[17,31]. In addition, women should be careful to stay hydrated while taking risankizumab to prevent dehydration, the mechanism of action remains unclear. As for the occurrence median time AEs induced by ustekinumab/risankizumab in different sex groups, There were differences between men and women in the ustekinumab group, onset of AEs was 155.5 days, 200 days, respectively. Therefore, when men take ustekinumab, they should be concerned about AEs earlier. The mechanism that causes the timing of AEs with ustekinumab to differ between genders is unclear. There was no significant difference in the occurrence time of AEs between risankizumab groups of different genders, both of them should be concerned about the occurrence of AEs in about 100 days. Our study has several limitations, mainly associated with disproportionality analysis studies. Underreporting of adverse events occurs in spontaneous reporting systems, and not all AEs related to a particular drug are reported to the FDA. If a particular AE was not reported in a clinical trial program, the reporter may not attribute it to that drug. Due to the lack of a denominator, it was not possible to accurately calculate the incidence of specific AE. Besides‌, limitations of disproportionality analyses include limited detailed demographic data, risk factors, comorbidities, and duration of exposure compared to formal epidemiological studies. Another limitation is that most AEs in the FAERS database were reported by customers, especially risankizumab. Therefore, the quality of the reports can not be guaranteed. In addition, given the attention risankizumab has received following FDA approval for the treatment of CD, there may be the possibility of overreporting of AEs. Furthermore, the smaller number of risankizumab reports as compared to ustekinumab may limit generalization. Finally, all signal detection results can only indicate a statistical correlation; Whether causality really exists needs further evaluation and research. Conclusion Our study investigated and analyzed AEs signals associated with ustekinumab and risankizumab based on the FAERS database to enhance clinical medication safety. The AEs identified in this study largely align with those documented in the ustekinumab’s and risankizumab's manual. Additionally, we uncovered AEs that were not previously listed, including clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab. These findings supplement the limited sample size of pre-market clinical studies. Gender-specific patients should be concerned about the occurrence of appropriate AEs when taking ustekinumab and risankizumab and our study provided evidence for ustekinumab and risankizumab in the treatment of CD. However, our study has limitations, we have not yet explored the correlation between ustekinumab-related/risankizumab-related AEs and the drug itself, underscoring the need to augment safety information. Further research is still warranted to elucidate the relationship between novel ustekinumab-related/risankizumab-related AEs and the drug and to refine ustekinumab and risankizumab’s safety profile. Abbreviations IL inhibits interleukin CD Crohn’s disease AEs adverse events FAERS United States Food and Drug Administration Adverse Event Reporting System ROR reporting odds ratio PRR proportional reporting ratio CI confidence interval IBD infammatory bowel disease SOC System Organ Classes Declarations Ethics approval and consent to participate Ethical approval and consent to participate was not required for this study because it used the FAERS database, which is a free open-access database. Consent for publication Not applicable. Availability of data and materials The original contributions presented in the study are included in the article or Supplementary Materials, further inquiries can be directed to the corresponding author. Competing interests The authors declare no competing interests. Funding None. Author contributions All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, J.X., C.T., and Y.C. designed the research; J.X., C.T., performed the research; J.X. and L.X. collected and analyzed data; J.X. and C.T. wrote the manuscript; J.X., C.T., L.X., and Y.C. critically revised the paper; L.X. and Y.C. final approved of the version to be published. All authors contributed to the article and approved the submitted version. Acknowledgements None. Authors' information 1 Department of pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing 400038, China. 2 Department of Pharmacy, Zigong Fourth People's Hospital, Zigong, Sichuan 643000, China. References Lightner AL, Vogel JD, Carmichael JC, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Crohn's Disease. Dis Colon Rectum. 2020;63:1028–52. 10.1097/DCR.0000000000001716 . 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J Anus Rectum Colon. 2021;;5:426–32. 10.23922/jarc.2021-021 . Published 2021 Oct 28. :. Tanaka T, Hirano D, Ishimaru S., et al. A Case of Ulcerative Colitis During Pregnancy and Childbirth at an Older Age While on Biologic Therapy. Cureus. 2024; 16: e66689. 2024. doi: 10.7759/cureus.66689 Foxman B. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infect Dis Clin North Am. 2014;;28:1–13. 10.1016/j.idc.2013.09.003 . :. Additional Declarations No competing interests reported. Supplementary Files SupplementaryData.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6189305","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":426556095,"identity":"6ec93570-2b7f-4146-b5d8-05997d9b9f60","order_by":0,"name":"Jiangchuan Xie","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiangchuan","middleName":"","lastName":"Xie","suffix":""},{"id":426556100,"identity":"1843bfcd-14fc-43eb-a5b2-da100b4b1d14","order_by":1,"name":"Chun Tao","email":"","orcid":"","institution":"Zigong Fourth People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Chun","middleName":"","lastName":"Tao","suffix":""},{"id":426556101,"identity":"c52a1da1-a520-4a7f-96fd-b90d378ced8a","order_by":2,"name":"Linli XIE","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Linli","middleName":"","lastName":"XIE","suffix":""},{"id":426556102,"identity":"bb823b76-c787-4094-8867-0d901e8ed23c","order_by":3,"name":"Yongchuan Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYPACGyjNRryWNAmStRwmQYv8jOzEzzw15+t0p50xYPhQdpiBf3YDfi2MM3I3S/Mcuy1hdjvHgHHGucMMEncO4NfCLJ27jZm3AaKFmbftMIOBRAJ+LWwQLecgWv4So4UHouUARAsjMVok5N9ulpxzLFly2+20goM959J5JG4Q0CLfc3bjhzc1dvxmt5M3PvhRZi3HP4OAFhBg4oEyDoBcSlg9EDD+IErZKBgFo2AUjFgAANFJPs4znG/rAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yongchuan","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-03-09 14:53:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6189305/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6189305/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":78347953,"identity":"4a83a703-11c7-4416-9dda-7365bc92a933","added_by":"auto","created_at":"2025-03-12 09:54:01","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":696156,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe top 20 PTs of the two drugs.(A)The top 20 PTs of ustekinumab;(B)The top 20 PTs of risankizumab.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/15fd9aadf3f2d39fef372047.png"},{"id":78347945,"identity":"3b738497-b826-412c-821e-8dbeafd96465","added_by":"auto","created_at":"2025-03-12 09:54:00","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":475152,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime to onset of drug-related AEs. (A) Ustekinumab-related onset of AEs; (B) risankizumab-related onset of AEs.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/683c39aad999a752e1701d63.png"},{"id":78347948,"identity":"105b6e47-a579-451c-ae0c-437640a65850","added_by":"auto","created_at":"2025-03-12 09:54:00","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":184871,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe top 10 AEs in different gender groups.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/74050ab6bc837f53a0082549.png"},{"id":78348353,"identity":"64f2deb7-6ff3-4315-a6d0-3f016fef34de","added_by":"auto","created_at":"2025-03-12 10:01:58","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":68435,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOnset of AEs induced by ustekinumab/risankizumab in different gender groups.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/2c13c05f652b03e0dbdbae7f.png"},{"id":95655052,"identity":"1f5acb67-500f-4e92-a3aa-3dca3131b86d","added_by":"auto","created_at":"2025-11-11 16:14:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3135472,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/2d4162c3-d756-4b7e-ad6f-c69f4f5a2873.pdf"},{"id":78347960,"identity":"1c831ab5-8984-40bf-8b58-5815b1eb3796","added_by":"auto","created_at":"2025-03-12 09:54:01","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":93361,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData.docx","url":"https://assets-eu.researchsquare.com/files/rs-6189305/v1/893f79d67e3fb882ae6fe55b.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors for humanized IgG1 monoclonal antibody in the treatment of Crohn's disease: pharmacovigilance of the FDA adverse event reporting system (FAERS)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCrohn’s disease(CD) is a chronic infammatory bowel disease(IBD) that can result in progressive bowel damage and disability[1]. CD is a global disease in the 21st century and it’s main symptoms include abdominal pain, diarrhea, fatigue, and weight loss[2]. The treatment principle of CD patients is to induce remission and maintain remission. Medical management for CD includes the categories of steroids, immunomodulators(thiopurines, methotrexate), TNFα antagonists(infliximab, adalimumab, certolizumab), Janus kinase inhibitors(upadacitinib), anti-integrin therapies(vedolizumab), interleukin(IL)-12/IL-23 inhibitors(ustekinumab, risankizumab)[2]. Despite the significance of TNF inhibitors in the treatment of CD, in clinical trials and practice, some patients do not respond to treatment and nearly half of the patients require increased doses after 12 weeks of treatment[3]. Therefore, risankizumab and ustekinumab entered everyone's field of vision.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRisankizumab and ustekinumab are both IgG1 monoclonal antibodies. The ustekinumab acts by binding to the p40 subunit shared by proinflammatory IL-23 and IL-12[4]. The studyshowed that for patients with non-response to anti-TNF treatment and immunosuppressive therapy failure or intolerance, ustekinumab group’s clinical remission rate was higher than the placebo group at week 3 and week 8, and the levels of C-reactive protein and fecal calprotectin were significantly improved and continuously decreased at week 3 of ustekinumab treatment[5]. One meta-analysis and systematic review study showed that ustekinumab provided clinical remission and improvement in patients with moderate to severe CD[6]. Two substudiesinvolving 252 patients showed more endoscopic improvements in patients treated with ustekinumab compared with placebo, and the mean histology activity scores decreased at week 8[7,8].Risankizumab acts by binding to the p19 subunit shared by proinflammatory IL-23[4]. Two placebo-controlled randomized controlled trial studiesshowed that patients with moderate to severe active CD, treated with risankizumab were more likely to achieve clinical response and clinical remission compared with placebo[9]. In addition, risankizumab was more likely to achieve endoscopic response and endoscopic remission than placebo[9]. In a subsequent trial of single maintenance therapy, more patients treated with risankizumab achieved clinical remission or endoscopic response compared with placebo[10,11].\u003c/p\u003e\n\u003cp\u003eClinical trial data suggest a favorable benefit-to-risk profile for IL-12/IL-23 inhibitors in CD. Researches showed that there was no significant difference between ustekinumab or risankizumab and placebo for AEs, serious adverse events(SAEs), or serious infection events[9,12]. AEs of concern for ustekinumab include infections, headache, nausea, arthralgia, injection site reactions, abdominal pain, pyrexia, nasopharyngitis, and fatigue[5], while AEs of concern for risankizumab include nasopharyngitis, arthralgia, headache, nausea, abdominal pain, diarrhoea, and anaemia[9]. In a head-to-head study[13], risankizumab demonstrated superiority in clinical response at week 24 and endoscopic response at week 48 compared with ustekinumab. In terms of safety, the percentages of patients who experienced any AEs, SAEs, or AEs that led to discontinuation of treatment were similar, and Covid-19 was the most frequently reported AE in both groups[13]. Although the proportion of SAEs was lower with risankizumab than with ustekinumab, the proportion of developed serious infections was similar in both groups[13].\u003c/p\u003e\n\u003cp\u003eWhile much has been learned about the efficacy and safety profile of ustekinumab and risankizumab in CD in clinical trials, there is a paucity of studies on comparative real-world safety profiles. The FDA Adverse Event Reporting System (FAERS) is one of the most representative self-reporting databases for AEs monitoring, which can help researchers identify new and potential AEs in the real world[14]. In this study, we evaluated AE reports for ustekinumab and risankizumab, aiming to evaluate potential associations between drugs and AE reports through FAERS data mining. Furthermore, it also aims to compare the AEs of two drugs in the real world and provide references for the clinical safety of drug use.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eData sources and procedures\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study collected ustekinumab’ AEs data from the FAERS Quarterly Data Extract Files between the third quarter of 2016 (FDA marketing approval of ustekinumab for the treatment of CD) and second quarter of 2024, and risankizumab data was collected from the second quarter of 2022 (FDA marketing approval of risankizumab for the treatment of CD) to the second quarter of 2024.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrug identification\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReports involving two humanized IgG1 monoclonal antibodies for CD: ustekinumab and risankizumab. During the data mining process, they were identified in the FAERS by brand and generic name.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, we assessed the relationship between AEs and humanized IgG1 monoclonal antibodies using the Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) using the contingency table calculator from Open Vigil. A risk signal was considered when the lower limit of the corresponding 95% CI was \u0026gt;1, a \u0026gt;3, and PRR ≥2 with an associated χ2 value of 4 or more. Table S1 shows the calculation formula. Data were analyzed using MYSQL (version 8.0) and R studio software (version 9.1.0).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Calculation of reporting odds ratio (ROR) and Proportional Reporting Ratio(PRR)\u003c/strong\u003e.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eItems\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eReports with target AE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eReports without target AE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eReports with ustekinumab/risankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eb\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eReports without ustekinumab/risankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ec\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ea+c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eb+d\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: a, number of reports containing both the target drug (ustekinumab/risankizumab) and target AE; b, number of reports containing other AEs of the target drug; c, number of reports containing the target AE of other drugs; d, number of reports containing other drugs and other AEs\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline characteristics of ustekinumab and risankizumab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics of AEs related to drug treatment of CD are shown in Table 2. For the treatment of CD, a total of 2,5223 AE reports were retrieved from FAERS, with 1,9753 for ustekinumab (Q3 of 2016-Q2 of 2024), and 5470 for risankizumab (Q2 of 2022-Q2 of 2024). In terms of gender, reports for females were approximately 20% more than males for two drugs. As for age composition, the highest proportion is 18-64.9 years old(48.9% for ustekinumab, 31.7% for risankizumab).\u0026nbsp;What\u0026apos;s more, hospitalization was the most common outcome for two drugs(22.2% for ustekinumab, 25.7% for risankizumab). The United States and Canada reported the highest number of AEs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 Clinical characteristics of reports with ustekinumab and risankizumab\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003efrom the FAERS database.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 35px;\"\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 35px;\"\u003e\n \u003cp\u003eRisankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 35px;\"\u003e\n \u003cp\u003eN=19753\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 35px;\"\u003e\n \u003cp\u003eN=5470\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e11378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e57.60%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3107\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e56.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e6945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e35.20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e38.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eUknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e7.20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e4.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003eWeight(kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e＜50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2.70%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e50-100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e4017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e20.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e1.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e＞100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2.90%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e7.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e14627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e74.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e5002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e91.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003eAge（year）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e＜18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e513\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e2.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e18～64.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e9664\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e48.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1733\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e31.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e65～85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1681\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e8.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e11.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e\u0026gt;85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e0.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e7844\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e39.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e56.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e0.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e962\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e4.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e2155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e10.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e2602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e13.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e5254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e26.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e2427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e12.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e2535\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e12.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e10.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e2582\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e13.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2778\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e50.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e5.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2094\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e38.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 100px;\"\u003e\n \u003cp\u003eOccupation of the reporter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eCustomer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e8323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e42.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4529\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e82.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eOther health-professional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16px;\"\u003e\n \u003cp\u003e5087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e25.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e8.70%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003eMedical Doctor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e3041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e15.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e374\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e6.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 29px;\"\u003e\n \u003cp\u003ePharmacists\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e8.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e1.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e1445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e7.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e1.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eunknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e7105\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e36.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e2261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e41.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eOther serious outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e7679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e38.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e1707\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e31.20%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eHospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e4377\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e22.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e1404\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e25.70%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e1.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e1.40%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eLife-threatening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e1.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eDisability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e0.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.20%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eRequired intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0.10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eCongenital Anomaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e0.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003eCountry of the reporter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eUnited States\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e10827\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e54.80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4525\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e82.70%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 29px;\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e4273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e21.60%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e782\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e14.30%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eothers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 16px;\"\u003e\n \u003cp\u003e4653\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003e23.60%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20px;\"\u003e\n \u003cp\u003e3.00%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisproportionality analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 3, the disproportionality at the system organ class (SOC) level of ustekinumab and risankizumab was observed in the FAERS. Ustekinumab-induced AEs presented eight areas of toxicity with statistically significant RORs and risankizumab-induced AEs presented eleven areas of toxicity. Of the statistically significant areas of toxicity, ustekinumab and risankizumab had five identical areas: nervous system disorders; product issues;\u0026nbsp;surgical and medical procedures; neoplasms benign, malignant and unspecified (incl cysts and polyps); hepatobiliary disorders, respectively. In addition, ustekinumab-induced AEs were statistically significant in three areas:\u0026nbsp;injury, poisoning and procedural complications; infections and infestations; congenital, familial and genetic disorders. Risankizumab-induced AEs were statistically significant in six areas: gastrointestinal disorders; general disorders and administration site conditions; metabolism and nutrition disorders; renal and urinary disorders; cardiac disorders; and ear and labyrinth disorders.\u003c/p\u003e\n\u003cp\u003eThere are 129/114 different preferred terms (PTs) of ustekinumab-associated/ risankizumab-associated AEs reported in the FAERS in at least 10 cases. The top 20 PTs of the two drugs are shown in Fig. 1. Table 4 lists the number of PTs in the top 10 for each corresponding SOC, including 69/95 PTs and 18/18 SOCs for ustekinumab/risankizumab, and others are described in Supplementary Table S2. Interestingly, among the 69/95 PTs, 50/77 PTs were classified as unexpected AEs in our data analysis, which were uncovered in the drug label and phase II/III clinical trial, such as clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3 Signal strength of AEs of ustekinumab and risankizumab at the system organ class (SOC) level in the FAERS database. (Quantity from high to low)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 49px;\"\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 50px;\"\u003e\n \u003cp\u003eRisankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*injury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e11544\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.69 ( 1.66 - 1.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*gastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e3655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.33 ( 1.28 - 1.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8509\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.78 ( 0.76 - 0.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*general disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e3132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.16 ( 1.11 - 1.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*infections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7583\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.77 ( 1.72 - 1.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1309\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.91 ( 0.86 - 0.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.69 ( 0.67 - 0.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*surgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e4.33 ( 4.06 - 4.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*nervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2725\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.23 ( 1.18 - 1.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*nervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1076\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.81 ( 1.7 - 1.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*product issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2661\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e8.14 ( 7.76 - 8.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e948\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.8 ( 0.75 - 0.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.55 ( 0.52 - 0.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e907\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.3 ( 0.28 - 0.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*surgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.77 ( 1.69 - 1.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e746\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.57 ( 0.53 - 0.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.84 ( 0.8 - 0.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e624\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.98 ( 0.9 - 1.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1632\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.4 ( 0.39 - 0.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e433\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.81 ( 0.73 - 0.89 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.72 ( 0.68 - 0.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003epsychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e306\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.85 ( 0.75 - 0.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*neoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.37 ( 1.28 - 1.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*metabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.33 ( 1.18 - 1.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003epsychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e788\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.62 ( 0.58 - 0.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*neoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e285\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.78 ( 1.57 - 2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e634\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.6 ( 0.56 - 0.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*product issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e2.39 ( 2.1 - 2.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eeye disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e454\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.65 ( 0.59 - 0.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.83 ( 0.74 - 0.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.53 ( 0.48 - 0.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*renal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e201\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.49 ( 1.3 - 1.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003erenal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e423\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.79 ( 0.72 - 0.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*hepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.67 ( 1.41 - 1.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*hepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e403\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.18 ( 1.07 - 1.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*cardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.27 ( 1.08 - 1.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.85 ( 0.76 - 0.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eeye disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.66 ( 0.56 - 0.78 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003ecardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e362\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.77 ( 0.7 - 0.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.78 ( 0.63 - 0.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.85 ( 0.75 - 0.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.02 ( 0.81 - 1.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.68 ( 0.59 - 0.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.85 ( 0.67 - 1.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.85 ( 0.73 - 0.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003e*ear and labyrinth disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.34 ( 1.05 - 1.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eear and labyrinth disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.69 ( 0.58 - 0.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003esocial circumstances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.56 ( 0.42 - 0.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003esocial circumstances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e121\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.49 ( 0.41 - 0.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.6 ( 0.4 - 0.89 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e*congenital, familial and genetic disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e1.74 ( 1.38 - 2.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003eendocrine disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.31 ( 0.82 - 2.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eendocrine disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18px;\"\u003e\n \u003cp\u003e0.76 ( 0.56 - 1.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20px;\"\u003e\n \u003cp\u003econgenital, familial and genetic disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.71 ( 0.37 - 1.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*indicates statistically significant signals in the algorithm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbbreviations: ROR, reporting odds ratio; CI, confidence interval.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4 Signal strength of the preferred term (PT) and the clinical priority assessing results.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"112%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eDrugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 44px;\"\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 40px;\"\u003e\n \u003cp\u003eRisankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eSOC\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003ePRR(\u0026chi;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003ePRR(\u0026chi;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einfusion related reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e511\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.85 ( 2.59 - 3.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.83 ( 513.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003efall*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.06 ( 1.68 - 2.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.05 ( 50.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einjection related reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e24.84 ( 13.79 - 44.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e24.83 ( 253.97 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eexposure via breast milk*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.38 ( 2.03 - 5.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.38 ( 24.77 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eanastomotic stenosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.32 ( 1.23 - 4.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.32 ( 7.19 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eskin abrasion*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.03 ( 1.05 - 3.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.03 ( 4.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eintestinal obstruction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.94 ( 3.49 - 4.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.89 ( 569.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esmall intestinal obstruction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.07 ( 3.22 - 5.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.05 ( 163.37 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eflatulence*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.59 ( 2.06 - 3.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.59 ( 70.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egastrointestinal sounds abnormal*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9.07 ( 6.99 - 11.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9.03 ( 407.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egastrointestinal haemorrhage*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.47 ( 2.91 - 6.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.47 ( 55.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eintestinal perforation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.91 ( 1.89 - 4.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.9 ( 26.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egastrointestinal obstruction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.91 ( 2.53 - 6.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.9 ( 43.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egastrointestinal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.29 ( 1.45 - 3.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.29 ( 13.51 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egastrointestinal scarring*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.27 ( 2.6 - 7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.26 ( 39.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003elarge intestine perforation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5.43 ( 3.06 - 9.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5.42 ( 42.48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esmall intestinal stenosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.53 ( 1.46 - 4.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.52 ( 11.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epneumonia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e575\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.35 ( 2.15 - 2.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.33 ( 382.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.11 ( 2.36 - 4.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.1 ( 71.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003elower respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e7.35 ( 6.6 - 8.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7.29 ( 1815.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eupper respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.58 ( 2.53 - 5.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.57 ( 59.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eclostridium difficile infection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e275\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.7 ( 2.37 - 3.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.69 ( 248.54 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ekidney infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.2 ( 1.41 - 3.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.2 ( 12.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eanal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.18 ( 1.88 - 2.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.18 ( 111.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ediverticulitis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.49 ( 1.59 - 3.89 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.49 ( 17.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecellulitis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.58 ( 2.16 - 3.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.57 ( 116.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epostoperative wound infection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.05 ( 1.92 - 4.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.05 ( 24.91 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ekidney infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e133\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4.42 ( 3.64 - 5.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.41 ( 272.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eabdominal abscess*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.18 ( 1.33 - 3.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.18 ( 10.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eabdominal abscess*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.69 ( 2.17 - 3.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.69 ( 88.77 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eappendicitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.79 ( 2.17 - 6.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.79 ( 25.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003egastrointestinal infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.14 ( 1.7 - 2.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.14 ( 44.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epost procedural infection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.11 ( 1.23 - 3.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.11 ( 7.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003etooth abscess*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.71 ( 2.91 - 4.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.71 ( 130.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003evascular device infection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.85 ( 2.05 - 7.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.85 ( 20.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eupper respiratory tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.19 ( 1.74 - 2.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.19 ( 46.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ebacteraemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5.31 ( 2.7 - 10.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5.31 ( 29.51 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003etherapeutic response decreased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e7.38 ( 6.44 - 8.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7.35 ( 1144.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site haemorrhage*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6.99 ( 5.76 - 8.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6.95 ( 521.17 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecomplication associated with device*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.74 ( 2.42 - 5.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.74 ( 40.39 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eunevaluable event*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.47 ( 3.61 - 5.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.44 ( 226.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003efeeling abnormal*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.6 ( 2.1 - 3.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.59 ( 82.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site erythema\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.46 ( 2.62 - 4.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.45 ( 87.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site papule\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e10.69 ( 7.59 - 15.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e10.66 ( 287.26 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eobstruction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.29 ( 3.14 - 5.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.29 ( 98.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehernia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.7 ( 1.99 - 3.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.69 ( 43.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.09 ( 2.97 - 5.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.08 ( 87.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.01 ( 2.75 - 5.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4 ( 61.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site pruritus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.03 ( 1.32 - 3.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.03 ( 10.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einjection site mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9.57 ( 5.9 - 15.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9.56 ( 126.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecerebrovascular accident\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.09 ( 1.7 - 2.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.09 ( 51.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eloss of consciousness*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.52 ( 3.56 - 5.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.51 ( 184.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003etransient ischaemic attack*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.4 ( 1.66 - 3.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.4 ( 23.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecerebrovascular accident*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.13 ( 3.09 - 5.51 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.12 ( 109.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003emultiple sclerosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.21 ( 1.47 - 3.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.21 ( 15.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eseizure*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.41 ( 3.2 - 6.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.4 ( 98.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003efacial paralysis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4.01 ( 2.58 - 6.23 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.01 ( 44.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epresyncope*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.88 ( 2.37 - 6.35 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.88 ( 33.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eposterior reversible encephalopathy syndrome*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e13.13 ( 7.53 - 22.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e13.13 ( 139.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003elethargy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.04 ( 1.21 - 3.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.04 ( 7.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecerebral haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.63 ( 1.49 - 4.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.63 ( 12.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ebalance disorder*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.08 ( 1.21 - 3.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.08 ( 7.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esensory disturbance*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.71 ( 1.5 - 4.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.71 ( 11.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehypersomnia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.59 ( 2.01 - 6.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.58 ( 21.52 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eidiopathic intracranial hypertension*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e8.07 ( 3.89 - 16.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8.07 ( 44.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003etransient ischaemic attack*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.82 ( 2.09 - 6.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.82 ( 22.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eischaemic stroke*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.65 ( 1.4 - 5.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.65 ( 9.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003emultiple sclerosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5.46 ( 2.95 - 10.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5.46 ( 36.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehead discomfort*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.43 ( 1.27 - 4.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.43 ( 7.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e*product issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esyringe issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e588\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e208.15 ( 153.21 - 282.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e205.92 ( 8353.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003edevice issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e217\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e8.03 ( 6.9 - 9.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7.93 ( 1032.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eneedle issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e547\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e36.69 ( 31.46 - 42.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e36.33 ( 5602 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eproduct quality issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.96 ( 2.16 - 7.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.95 ( 23.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edevice issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e336\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.72 ( 1.54 - 1.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1.72 ( 90.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edevice deployment issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e248.75 ( 135.28 - 457.4 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e247.94 ( 2547.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edevice malfunction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e17.62 ( 13.9 - 22.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e17.58 ( 1066.54 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edevice defective*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e35.12 ( 25.26 - 48.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e35.05 ( 1171.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eproduct leakage*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e49.3 ( 32.93 - 73.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e49.21 ( 1115.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edrug delivery system malfunction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e49.38 ( 31.51 - 77.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e49.31 ( 901.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eliquid product physical issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e15.63 ( 11.41 - 21.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e15.61 ( 529.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eproduct packaging issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e43.07 ( 27.02 - 68.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e43.02 ( 725.26 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eintestinal resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e419\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.38 ( 3.04 - 3.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.36 ( 571.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esurgery*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9.74 ( 8.29 - 11.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e9.64 ( 1154.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.63 ( 2.31 - 2.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.62 ( 230.48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eintestinal resection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.69 ( 3.78 - 5.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.67 ( 240.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecolectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.25 ( 1.89 - 2.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.25 ( 85.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecolectomy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e7.58 ( 5.96 - 9.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7.55 ( 378.03 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003etherapy cessation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.77 ( 2.91 - 4.9 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.77 ( 114.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eileostomy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.86 ( 3.69 - 6.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.85 ( 154.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esmall intestinal resection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.44 ( 1.85 - 3.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.44 ( 42.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehospitalisation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.13 ( 1.62 - 2.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.13 ( 30.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eintestinal operation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.65 ( 1.98 - 3.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.65 ( 45.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eostomy bag placement*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e18.01 ( 11.94 - 27.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e17.98 ( 364.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eileectomy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.88 ( 1.88 - 4.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.87 ( 25.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003estoma creation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e8.07 ( 5.51 - 11.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e8.05 ( 164.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecaesarean section*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.09 ( 1.34 - 3.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.09 ( 11.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esmall intestinal resection*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e7.13 ( 4.89 - 10.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e7.11 ( 143.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecolectomy total*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4 ( 2.47 - 6.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.99 ( 37.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecolostomy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.82 ( 3.15 - 7.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.81 ( 64.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eproctectomy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.01 ( 1.79 - 5.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.01 ( 19.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eintestinal operation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.33 ( 2.82 - 6.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.33 ( 53.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eskin reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.14 ( 1.34 - 3.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.14 ( 10.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehyperhidrosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.53 ( 1.87 - 3.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.53 ( 38.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003erash papular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.85 ( 1.61 - 5.03 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.84 ( 14.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eliver function test abnormal*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.17 ( 2.02 - 4.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.16 ( 28.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehaemoglobin decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.12 ( 1.51 - 2.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.12 ( 19.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003egeneral physical condition abnormal*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.43 ( 1.32 - 4.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.43 ( 8.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esars-cov-2 test positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.51 ( 1.67 - 3.78 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.51 ( 20.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eblood potassium decreased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.59 ( 2.32 - 5.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.58 ( 38.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ewhite blood cell count increased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.04 ( 1.28 - 3.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.04 ( 9.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003efull blood count decreased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.04 ( 7.08 - 24.01 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e13.03 ( 114.55 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eblood magnesium decreased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.4 ( 1.96 - 5.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.4 ( 21.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einflammatory marker increased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.09 ( 1.78 - 5.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.09 ( 17.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eblood glucose increased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.24 ( 1.83 - 5.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.24 ( 18.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ealanine aminotransferase increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.54 ( 1.44 - 4.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.54 ( 11.11 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ewhite blood cell count decreased*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.5 ( 1.35 - 4.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.5 ( 9.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epharyngeal swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.82 ( 1.73 - 4.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.82 ( 18.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epulmonary embolism*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.1 ( 2.1 - 4.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.1 ( 35.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einterstitial lung disease*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.3 ( 1.38 - 3.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.3 ( 10.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epulmonary thrombosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e15.07 ( 8.88 - 25.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e15.05 ( 180.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epneumonitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.14 ( 1.25 - 3.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.14 ( 8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ethroat tightness*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.28 ( 1.32 - 3.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.28 ( 9.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003edry throat\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.12 ( 1.13 - 3.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.12 ( 5.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003epneumothorax*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5.01 ( 2.64 - 9.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e5.01 ( 30.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ebreast cancer*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.49 ( 1.88 - 3.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.49 ( 43.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eneoplasm malignant*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.27 ( 1.5 - 3.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.27 ( 15.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esquamous cell carcinoma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.18 ( 1.53 - 3.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.17 ( 19.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ebreast cancer female*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.51 ( 2.57 - 7.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.51 ( 33.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003egastrointestinal carcinoma*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.14 ( 1.34 - 3.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.14 ( 10.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003emalignant melanoma*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.48 ( 1.37 - 4.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.47 ( 9.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epancreatic carcinoma*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.22 ( 1.81 - 5.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.22 ( 17.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecolon cancer*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.85 ( 2.05 - 7.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.85 ( 20.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ehepatic cancer*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.36 ( 1.31 - 4.23 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.36 ( 8.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003elung neoplasm malignant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.37 ( 1.24 - 4.52 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.37 ( 7.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eanal cancer*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.49 ( 1.27 - 4.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.49 ( 7.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003epsychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003emood swings*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.34 ( 1.36 - 4.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.33 ( 9.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einsomnia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.16 ( 1.74 - 2.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.15 ( 50.52 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003esuicidal ideation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.72 ( 1.47 - 5.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.72 ( 10.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehypotension*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.18 ( 1.59 - 2.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.18 ( 24.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ethrombosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.96 ( 2.09 - 4.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.96 ( 41.19 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003einternal haemorrhage*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.99 ( 2.7 - 9.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.99 ( 32.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003edehydration*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.82 ( 2.26 - 3.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.81 ( 94.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehypophagia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.62 ( 2.39 - 5.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.62 ( 42.1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003erenal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eiga nephropathy*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.34 ( 1.36 - 4.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.33 ( 9.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003erenal failure*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.26 ( 2.07 - 5.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.25 ( 29.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003edysuria*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.28 ( 1.32 - 3.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.28 ( 9.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003echromaturia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6.21 ( 3.41 - 11.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6.21 ( 46.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003ehepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003echolelithiasis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.03 ( 1.6 - 2.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.03 ( 34.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehepatic cirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.39 ( 1.6 - 3.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.39 ( 19.39 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003echolecystitis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.65 ( 1.56 - 4.51 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.65 ( 14.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003echolelithiasis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.09 ( 1.29 - 3.37 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.09 ( 9.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ehepatic function abnormal*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4.06 ( 2.3 - 7.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e4.05 ( 27.33 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehepatic steatosis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.99 ( 1.76 - 5.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.99 ( 17.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003egallbladder disorder*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.94 ( 1.66 - 5.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.93 ( 15.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eanaphylactic reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.68 ( 2.12 - 3.39 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.68 ( 72.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ecardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003emyocardial infarction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.92 ( 1.92 - 4.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.92 ( 27.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecardiac disorder*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.06 ( 1.29 - 3.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.06 ( 9.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003eatrial fibrillation*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.32 ( 1.42 - 3.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.32 ( 11.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ecardiac failure congestive*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6.18 ( 3.47 - 11.01 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e6.17 ( 49.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ethrombocytopenia*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.19 ( 1.41 - 3.39 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.19 ( 12.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eerectile dysfunction*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.02 ( 1.53 - 5.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e3.02 ( 11.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003epremature labour*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.87 ( 1.51 - 5.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.87 ( 11.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eear and labyrinth disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003ehypoacusis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.63 ( 1.49 - 4.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.62 ( 11.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003esocial circumstances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003einsurance issue*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.21 ( 1.48 - 3.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e2.21 ( 15.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 8px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 9px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*PTs uncovered by drug package insert and phase II/III clinical trials\u0026nbsp;\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTime-to-onset analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe time from ustekinumab or risankizumab use to AEs occurrence was assessed and shown in Fig. 2. The median time to the ustekinumab-related onset of AEs was 195 days (IQR 56 - 505.5 days), and ＞360 days, 181-360 days, and 0-30 days after medication accounted for 33.1% and 18.9%, 16.2% respectively. The median time to the risankizumab-related onset of AEs was 105 days (IQR 42.25 - 214 days), 181-360 days and 0-30 days after medication accounted for 24.4% and 19.3%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGender subgroup analysis\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs shown in Table 5, there are similarities and differences in the presentation of ustekinumab-related and risankizumab-related AEs in males and females. Negative signals are detailed in Supplementary Table S3.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5 Positive SOC signal in patients of different genders.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"102%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 43px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 46px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003eDrug\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 10px;\"\u003e\n \u003cp\u003eUstekinumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6774\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.01 ( 1.95 - 2.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4073\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.96 ( 1.89 - 2.03 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4561\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.76 ( 1.71 - 1.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e2427\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.78 ( 1.7 - 1.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.21 ( 1.15 - 1.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eproduct issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e6.15 ( 5.69 - 6.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eproduct issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1489\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e6.91 ( 6.48 - 7.37 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e830\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.15 ( 1.07 - 1.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.58 ( 1.49 - 1.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e721\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.53 ( 1.41 - 1.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified (incl cysts and polyps)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.21 ( 1.1 - 1.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003epregnancy, puerperium and perinatal conditions*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2.23 ( 1.35 - 3.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"10\" style=\"width: 10px;\"\u003e\n \u003cp\u003eRisankizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003egastrointestinal disorders*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e2181\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.15 ( 1.1 - 1.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.12 ( 1.05 - 1.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1890\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.17 ( 1.12 - 1.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3.64 ( 3.28 - 4.03 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e690\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3.93 ( 3.62 - 4.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e411\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.94 ( 1.75 - 2.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e639\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.64 ( 1.51 - 1.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.35 ( 1.12 - 1.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.18 ( 1.01 - 1.37 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eproduct issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.81 ( 1.49 - 2.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.59 ( 1.34 - 1.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.35 ( 1.11 - 1.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eproduct issues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.81 ( 1.52 - 2.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003ehepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.75 ( 1.37 - 2.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003erenal and urinary disorders*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.6 ( 1.32 - 1.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003ecardiac disorders*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.3 ( 1.01 - 1.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003ehepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.28 ( 1.02 - 1.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 22px;\"\u003e\n \u003cp\u003eear and labyrinth disorders*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 10px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.6 ( 1.2 - 2.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Different positive SOC signals in patients of different genders\u003c/p\u003e\n\u003cp\u003eFor ustekinumab, female-induced AEs were statistically significant in neoplasms benign, malignant and unspecified (incl cysts and polyps) (n=523, ROR=1.21, 95% CI=1.10-1.32). In contrast, male-induced AEs were statistically significant in pregnancy, puerperium and perinatal conditions(n=18, ROR=2.23, 95% CI=1.35-3.67).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor risankizumab, female-induced AEs were statistically significant in gastrointestinal disorders(n=2181, ROR\u0026nbsp;1.15, 95% CI: 1.10 - 1.21), renal and urinary disorders(n=111, ROR\u0026nbsp;1.60, 95% CI:\u0026nbsp;1.32 - 1.94), and\u0026nbsp;ear and labyrinth disorders(n=50, ROR\u0026nbsp;1.60, 95% CI:1.20 - 2.14\u0026nbsp;), while male-induced AEs were statistically significant in cardiac disorders(n=68, ROR 1.30, 95% CI:1.01-1.67).\u003c/p\u003e\n\u003cp\u003eWe compared PTs induced by ustekinumab/risankizumab in different gender groups, the top 10 PTs in each subgroup are shown in Fig. 3, and others are detailed in Supplementary Table S4. The PTs of females were different from males when taking ustekinumab: exposure during pregnancy(n=291, ROR 3.20, 95% CI: 2.81 - 3.64), clostridium difficile infection(n=149, ROR 2.26, 95% CI: 1.90 - 2.29). Simultaneously, The different PTs of males were: surgery(n=111, ROR 2.37, 95% CI: 1.94 - 2.91), anal abscess(n=94, ROR 2.36, 95% CI: 1.89 - 2.94). As for risankizumab, PTs of females were: urinary tract infection(n=71, ROR 2.14, 95% CI: 1.68 - 2.74); intestinal resection(n=62, ROR 5.13, 95% CI: 3.89 - 6.78); dehydration(n=59, ROR 2.87, 95% CI: 2.19 - 3.77); feeling abnormal(n=57, ROR 2.77, 95% CI: 2.10 - 3.65); small intestinal obstruction(n=55, ROR 4.27, 95% CI: 3.19 - 5.71); loss of consciousness(n=49, ROR 5.00, 95% CI: 3.66 - 6.82). In contrast, PTs of males were: dizziness(n=72, ROR 2.67, 95% CI: 2.08 - 3.42); fall(n=40, ROR 2.06, 95% CI: 1.48 - 2.86); colectomy(n=39, ROR 7.14, 95% CI: 4.92 - 10.38); insomnia(n=36, ROR 2.56, 95% CI: 1.80 - 3.64); gastrointestinal disorder(n=34, ROR 2.01, 95% CI: 1.41 - 2.88); flatulence(n=34, ROR 2.01, 95% CI: 1.41 - 2.87).\u003c/p\u003e\n\u003cp\u003eWe also compared the occurrence of AEs induced by ustekinumab/risankizumab in different sex groups, and the results showed that the median time to the ustekinumab-female group, ustekinumab-male group, ustekinumab-female group, risankizumab-female group, risankizumab-male group, onset of AEs was 155.5 days (IQR 50 - 379 days), 200 days (IQR 55 - 491 days), 103 days (IQR 42 - 214 days), 110 days (IQR 44 - 218.5 days), respectively, as shown in Fig. 4.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe results of this study showed that there were commonalities and significant differences between ustekinumab and\u0026nbsp;risankizumab in reported AEs. Both sets of data showed that the patients were predominantly female, which may be related to the high incidence of CD in girls and women[15].\u0026nbsp;Furthermore, the proportion of 18-64.9 years was the highest in both sets of data, consistent with research findings[16,17], which may be related to the age distribution of CD onset[16].\u0026nbsp;The age distribution may be related to the fact that CD was a chronic disease that can only be induced and maintained in remission with treat-to-target, not cured, and patients at every age may report AEs. SAEs in both groups were mainly leading to hospitalization.\u003c/p\u003e\n\u003cp\u003eIn this study, 69 signals involving 18 SOC of ustekinumab were mined, including injury, poisoning and procedural complications, gastrointestinal disorders, infections and infestations, general disorders and administration site conditions, nervous system disorders, product issues, surgical and medical procedures, skin and subcutaneous tissue disorders, investigations, respiratory, thoracic and mediastinal disorders, neoplasms benign, malignant and unspecified (incl cysts and polyps), etc. While 95 signals involving 18 SOC of risankizumab were mined, including gastrointestinal disorders, general disorders and administration site conditions, infections and infestations, surgical and medical procedures, nervous system disorders, musculoskeletal and connective tissue disorders, injury, poisoning and procedural complications, investigations, skin and subcutaneous tissue disorders, respiratory, thoracic and mediastinal disorders, psychiatric disorders, etc.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor ustekinumab, high-frequency SOCs were primarily observed in reactions such as injury,\u0026nbsp;poisoning and procedural complications, infections and infestations, general disorders and administration site conditions, and nervous system disorders, basically consistent with the results of phase III clinical trials[5]. The injury, poisoning and procedural complications systems with a higher frequency of occurrence in these systems include infusion-related reaction, injection-related reaction, and exposure via breast milk; infections and infestations include pneumonia, lower respiratory tract infection, and clostridium difficile infection; cerebrovascular accident, transient ischaemic attack, and multiple sclerosis have a higher frequency of occurrence in nervous system disorders. These AEs are commonly reported in clinical studies and package inserts[5,13,18,19]. Infusion-related reaction was the most common AE in the injury, poisoning and procedural complications system, consistent with previous research[5,13]. Infusion-related AEs caused by ustekinumab have been reported in some cases[20,21]. Infusion-related reactions, injection-related reactions, therapeutic response decreased, and incomplete dose administration that were not included in the package insert, and clinical trial studies as causally associated with ustekinumab use were found to be related to complex dosing procedures, wrong administration procedures, or technical problems with the device. These findings suggest that by improving the device and optimizing the dosing schedule, some of these AEs can be avoided and the efficacy and safety of ustekinumab can be improved. Pneumonia, and lower respiratory tract infection were the most common AE in the infections and infestations system, consistent with previous research[5,13,17,18,22]. In addition, clinical studies have identified upper respiratory tract inflammation, anal abscess, kidney infection, kidney infection, gastrointestinal infection, etc. caused by ustekinumab, consistent with our findings, and can cause serious infections\u003csup\u003e[\u003c/sup\u003e\u003csup\u003e5,13,22-25]\u003c/sup\u003e. Therefore, we should pay attention to infection-related symptoms, signs and examination indicators in the process of medication, and use antibiotics promptly.\u0026nbsp;Central nervous system AEs caused by ustekinumab have been reported in the literature\u003csup\u003e[5]\u003c/sup\u003e, cerebrovascular accident was the most common AE in the nervous system disorders, it has been reported in the literature[5,26-27]. Therefore, we should pay close attention to related symptoms during medication.\u003c/p\u003e\n\u003cp\u003eRisankizumab’s SOC was primarily observed in gastrointestinal disorders, general disorders and administration site conditions, and surgical and medical procedures, consistent with the results of phase III clinical trials[9]. The\u0026nbsp;gastrointestinal disorders systems\u0026nbsp;with a higher frequency of occurrence in these systems include intestinal obstruction, small intestinal obstruction, and flatulence; general disorders and administration site conditions include injection site haemorrhage, injection site erythema, injection site papule, and injection site swelling; surgery, intestinal resection, and colectomy have a higher frequency of occurrence in surgical and medical procedures. These AEs are commonly reported in clinical studies and package inserts[9,13,18]. Clinical trials have shown that in addition to being caused by drugs, AEs of gastrointestinal disorders may also be related to the aggravation of clinical manifestations of CD[9]. Infusion-related AEs caused by risankizumab have been extensively reported in the literature[9,13,17], which should be paid attention to, and pretreatment should be done before use if necessary. Surgery, intestinal resection, and colectomy were closely associated with CD progression requiring surgery[2].\u003c/p\u003e\n\u003cp\u003eAccording to the disproportionality analysis, many organs or tissues were involved, although some AEs were reported more frequently than others. As shown in Figure 2, significant AEs of ustekinumab mainly included syringe issues, pneumonia, needle issue, infusion-related reactions, lower respiratory tract infection, and intestinal resection. ‌‌\u003ca href=\"https://www.baidu.com/s?wd=however\u0026amp;rsv_idx=2\u0026amp;tn=40020637_29_oem_dg\u0026amp;usm=4\u0026amp;ie=utf-8\u0026amp;rsv_pq=a4c26e4300003106\u0026amp;oq=%E8%8B%B1%E8%AF%AD%E4%B8%AD%E8%A1%A8%E7%A4%BA%E8%BD%AC%E6%8A%98%E7%9A%84%E8%AF%8D%E6%B1%87\u0026amp;rsv_t=fc09YszzbiXiIrbJYbNxOvd1gRIJPyLR3qyHQeaKsMasFlownKE6rAUZCFFBHMTjMwA2VZQAq/zp\u0026amp;sa=re_dqa_generate\" target=\"https://www.baidu.com/_self\"\u003eHowever\u003c/a\u003e, only lower respiratory tract infection and infusion-related reactions were reported in the package insert and clinical trial studies[5,13]. Significant AEs of risankizumab mainly included intestinal obstruction, device issue, surgery, injection site haemorrhage, fall, and unevaluable event. ‌\u003cstrong\u003e‌\u003c/strong\u003e\u003cstrong\u003e\u003ca href=\"https://www.baidu.com/s?wd=whereas\u0026amp;rsv_idx=2\u0026amp;tn=40020637_29_oem_dg\u0026amp;usm=4\u0026amp;ie=utf-8\u0026amp;rsv_pq=a4c26e4300003106\u0026amp;oq=%E8%8B%B1%E8%AF%AD%E4%B8%AD%E8%A1%A8%E7%A4%BA%E8%BD%AC%E6%8A%98%E7%9A%84%E8%AF%8D%E6%B1%87\u0026amp;rsv_t=79f8QMi5XKkp1I7InabL3O7IUKLZK7L60oNImBnw9hI6gYWBIozc6jFk034k8AnrrcxINoARkU9z\u0026amp;sa=re_dqa_generate\" target=\"https://www.baidu.com/_self\"\u003e\u003cstrong\u003eW\u003c/strong\u003ehereas\u003c/a\u003e\u003c/strong\u003e, only injection site haemorrhage was not reported in the package insert and clinical trial studies[28]. In addition, we identified many new PTs for ustekinumab and risankizumab, therefore, we should pay attention not only to the package insert AEs, but also to the AEs that are not recorded. Moreover‌, the common SOC and PT signals of the two drugs were not completely consistent, and we can choose personalized medication according to the different organ function states of the patient to ensure safety. The disproportionation signals were found to be biologically plausible, based on preclinical or clinical studies providing pharmacological evidence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study found similarities and differences in PTs between the two drugs. In terms of infections and infestations, ustekinumab had a higher incidence than risankizumab. In addition, PT signals of ustekinumab were identified between different infections such as pneumonia, lower respiratory tract infection, clostridium difficile infection, anal abscess, cellulitis, and tooth abscess, whereas none of these signals were seen with risankizumab. Although speculative, this might suggest that ustekinumab——as a “Dual targeting Inhibitors”, may lead to an increased risk of infection[18,29,30]. Theoretically, the use of any immunosuppressant in the treatment of inflammatory disease may lead to impaired host immune function against pathogens. IL-12 and IL-23 influenced the response of T\u003csub\u003eH\u003c/sub\u003e1 cells and T\u003csub\u003eH\u003c/sub\u003e17 cells respectively to increase the risk of infection[18]. Emerging data from human loss-of-function variants and preclinical studies in mice suggest the relative risk of infection associated with targeting IL-12 and/or IL-23[18]. Therefore, more attention should be paid to secondary infection during the use of ustekinumab.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe results of the disproportionality analysis study showed that risankizumab and ustekinumab were associated with a clear cerebrovascular accident signal, which was consistent with our findings[17,31]. Interestingly, the cerebrovascular accident signal of these two drugs was not reported in the package insert. For example, PTs such as cerebrovascular accident, transient ischaemic attack, etc., were seen in the ustekinumab, and PTs such as cerebrovascular accident, transient ischaemic attack, etc., were found in the risankizumab. In addition, in risankizumab, falls, presyncope, loss of consciousness, and balance disorder may also be directly related to cerebrovascular accidents. Although theories have been proposed, the clear biologically plausible mechanisms by which risankizumab and/or IL-23 inhibition affect the risk of cerebrovascular accident have not been elucidated in the literature. Some animal studies have shown that IL-23 inhibition does not have a protective effect on atherosclerotic plaque formation[32,33]. Inhibition of IL-23 can also inhibit the production of IL-17 by T cells[34]. IL-17 has been found to significantly limit the development of atherosclerotic lesions, and increased levels of IL-17A were associated with the stability of atherosclerotic plaques, and low serum IL-17 levels were further associated with an increased risk of death and recurrent major adverse cardiac events[35,36]. Thus, in theory, lower circulating IL-17 levels after IL-23 inhibition could contribute to atherosclerotic plaque formation and/or destabilization, thereby contributing to cerebrovascular accidents[31]. Although further studies are needed to identify clear mechanisms by which IL-23 inhibition causes or promotes cerebrovascular accidents, close attention should be paid to cerebrovascular accidents during the use of ustekinumab or risankizumab.\u003c/p\u003e\n\u003cp\u003eMalignant disproportionality signals were identified for both drugs. Preclinical animal studies have shown that IL-12 and IL-23 can inhibit tumor growth[37]. Moreover, Malignancies have been reported for ustekinumab and risankizumab in both clinical trials and postmarketing studies for the treatment of CD[10,38,39]. Numerous studies have shown that inhibiting IL-12 may lead to tumor growth. In mouse tests, antigen-presenting cells produce IL-12, and its downstream mediators are critical for anti-tumor immunity[18]. IL-12p35-deficient mice had a higher susceptibility to carcinogens-induced skin papilloma formation than wild-type mice, and tumor incidence and tumor growth were higher in IL-12/23p40-deficient mice than in wild-type controls[18]. The role of IL-23 may be more complex, and its role in tumors still needs to be further studied. IL-23 may have a tumor-suppressive effect on UV-radiation-induced skin-active cancer in mouse models[40]. The IL-12-IL-23 axis plays an important role in controlling the equilibrium phase of cancer immunoediting[41], which is best characterized in a methylcholanthrene-A-induced mouse fibrosarcoma model[42].\u003c/p\u003e\n\u003cp\u003eThe gastrointestinal system that we only found in risankizumab such as iintestinal obstruction, small intestinal obstruction, flatulence, and gastrointestinal sounds abnormal have been identified in this study. Head-to-head studiesin patients with moderate-to-severe CD have shown higher SAEs rates with risankizumab compared with ustekinumab, attributed to SAEs in the gastrointestinal disorders system organ class[13]. Both our statistical findings and clinical trials suggest that gastrointestinal disorders are characteristic AEs of risankizumab[13]. These AEs may be attributed to a higher affinity of risankizumab for IL-23 and an increased potency for its inhibition[43]. A large number of studieshave confirmed the role of IL-23 in mucosal homeostasis[4,44,45], but the functional role of IL-12 in the healthy gut remains unclear, which may support the concept that IL-12 is not necessary to maintain homeostatic conditions in the gut[46,47].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDisproportionality and high-frequency signals involving the product issues that we only found in ustekinumab such as syringe issues, needle issues, device deployment issues, device malfunction, device defective, and product leakage have been identified in this study. This further confirmed the complexity of the ustekinumab delivery device, and the need for improved delivery devices. The infusion-related reaction we only found in ustekinumab, to reduce this AEs, risankizumab may be a better choice, or pretreatment before administration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnexpected and\u0026nbsp;significant safety signals\u0026nbsp;of\u0026nbsp;ustekinumab, such as\u0026nbsp;investigations, psychiatric disorders, renal and urinary disorders, hepatobiliary disorders, blood and lymphatic system disorders, were detected in our analysis. For risankizumab,\u0026nbsp;unexpected and significant safety signals, such as\u0026nbsp;investigations, psychiatric disorders, vascular disorders, metabolism and nutrition disorders, renal and urinary disorders, hepatobiliary disorders, cardiac disorders, were detected in our analysis. However, these AEs are not explicitly mentioned in the ustekinumab or risankizumab package insert.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnexpected and significant safety PT signals involved in ustekinumab, in order of the number of cases, are cholelithiasis, liver function test abnormal, thrombocytopenia, cholecystitis, iga nephropathy, mood swings. Liver function abnormal[13,48], thrombocytopenia[49-50], and iga nephropathy[51], have been reported in the literature. There is currently no data on ustekinumab-related liver damage in IBD patients. Only a retrospective study analyzing the effects of ustekinumab on 44 patients with psoriasis showed only a mild elevation of aminotransferase in 6 cases[48]. However, experience with its use was limited, therefore, further studies are needed to confirm these data. Elevated levels of IL-23 and IL-17 have been demonstrated in immune thrombocytopenia[52]. However, the mechanism of action of IL-23/IL-17 in normal platelet homeostasis remains unclear. Iga nephropathy was typically characterized by a higher proportion of circulating Th2 rather than Th1[53]. Studies have shown that Th2-associated IL-4 amplifies the formation of Gd-IgA1 by altering the terminal glycosylation that secretes diga1[54]. Thus, it may be that the administration of ustekinumab optimized the immune abnormality of Th1 dominance, leading to a state of Th-2 comparative dominance. This ustekinumab pharmacologically induced mutation of T cell subsets may induce crescent-shaped IgAN by amplifying the formation of Gd-IgA1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnexpected and significant safety PT signals involved in risankizumab, in order of the number of cases, are dehydration, insomnia, hypotension, haemoglobin decreased, thrombosis, SARS-CoV-2 test positive, and blood potassium decreased. Thrombosis[55], and SARS-CoV-2 test positive[13], have been reported in the literature. SARS-CoV-2 positivity is associated with the background of COVID-19 and suppressed immune function[18]. The AEs of dehydration, insomnia, hypotension, haemoglobin decreased, and blood potassium decreased have not been reported in the literature, and the mechanism remains to be further studied. Dehydration was the high-frequency PT signal observed in risankizumab, so hydration during risankizumab administration is recommended to prevent dehydration. Thrombosis may be associated with the inhibition of IL-23 by risankizumab and may be associated with atherosclerotic plaque formation and/or destabilization[17,35,36]. Therefore, the newly emerging signals of ustekinumab, particularly cholelithiasis, liver function test abnormal, and thrombocytopenia, need to be given a great deal of attention. While the newly emerging signals of risankizumab, particularly dehydration, insomnia, and haemoglobin decreased, need to be given a great deal of attention. We can choose these two drugs individually according to the different organ function status and laboratory examination indicators of patients. For example, when patients have low hemoglobin or potassium levels, ustekinumab is preferred over risankizumab. And risankizumab may be a better choice if the patient has hepatobiliary disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA statistical analysis of the timeline for AEs was conducted for both drugs, the results showed that the median time to occurrence of AEs after initial treatment with ustekinumab and risankizumab was 195 days and 105 days, respectively, basically consistent with the literature report[17].Only approximately 30% of AEs occurred within 60 days with both drugs, which makes it important to pay attention to AEs that occur during the whole course of medication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe performed a subgroup analysis of sex to examine similarities and differences in AE between the two drugs in gender-specific populations. Patients of different genders have different physiological conditions, and they respond to drugs also differently. Studies showed that male sex was an independent factor in the increased dose demand for ustekinumab for IBD, and gender significantly influenced ustekinumab disposition[56,57]. Therefore, there may be differences in AEs between genders. In ustekinumab, we only found a statistically significant signal of neoplasms benign, malignant and unspecified in females, so when women were treated with ustekinumab for CD, more attention should be paid to AEs related to neoplasms benign, malignant and unspecified.\u0026nbsp;No studies have been found to report this gender difference, and further studies are needed. In ustekinumab, we also only found a statistically\u0026nbsp;significant\u0026nbsp;signal of\u0026nbsp;pregnancy, puerperium and perinatal conditions\u0026nbsp;in males. The drug insert states that no effect on fertility was observed in male cynomolgus monkeys administered with high doses of ustekinumab twice a week prior to and during the mating period. And study showed thatsemen quality and sperm DNA integrity were not affected after male patients were treated with ustekinumab[58], so men who wish to have children can continue using ustekinumab, however, the study objects were small, and the package insert only contain male animal data. Conversely, Our study was a real-world clinical safety study, has a large amount of data, and the number of male patients using ustekinumab is as high as 6945, including multiple species and multiple countries, which has clinical significance, but the specific mechanism has not been reported, and further research is needed. Combined with the results of this study, we believe that men should pay attention to contraception during the use of ustekinumab.\u0026nbsp;According to the results of this study, during the use of\u0026nbsp;risankizumab, women should pay attention to gastrointestinal disorders, renal and urinary disorders, and ear and labyrinth disorders, while men should be concerned about cardiac disorders. For\u0026nbsp;risankizumab, no gender differences in AEs were reported,\u0026nbsp;and further research is needed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe also compared PTs induced by ustekinumab/risankizumab in different gender groups. As can be seen from Figure 4, whether it's the ustekinumab-female subgroup or the ustekinumab-male subgroup, the top PTs were pneumonia, lower respiratory tract infection, syringe issue, infusion-related reaction, and needle issue. Therefore, no matter whether men or women use ustekinumab, they should be concerned about these AEs. In the same way, men and women should be concerned about intestinal obstruction, surgery, device issue, and injection site haemorrhage. Among the female group of two drugs ranked the top 10 PTs, exposure during pregnancy was only found in the ustekinumab-female group, so we should pay more attention to the use of ustekinumab in women during pregnancy. The use of IBD drugs during pregnancy was usually done when it is considered that the benefits outweigh the potential risks of AEs, teratogenicity, and fetal toxicity. Studies have shown that the use of immunomodulators was not associated with the occurrence of pregnancy and birth abnormalities[59]. As mentioned in the package insert, no effects on the fertility of female mice were observed with high doses of IL-12/IL-23p40 antibody prior to and during early pregnancy. However, biologics agents were transferred through the placenta into the neonatal blood in the third trimester (after 30 weeks), some reports recommend that biologics should be avoided in the third trimester, the reason was that the effects of ustekinumab present in the neonatal blood on the development of the neonatal immune system have not been fully elucidated[59,60]. In addition, if ustekinumab was used in the third trimester, the question of whether the newborn will be vaccinated after birth was also a major concern[61]. In a case report of CD treated with ustekinumab until the third trimester, ustekinumab was detected in both maternal blood and umbilical cord blood but was not detected in a 6-month-old infant[60]. However, there were few case studies and literature reports on the effects of ustekinumab on the fetus, and further studies are needed. In the ustekinumab group, the number of female patients with urinary tract infections was higher, which may be related to the high incidence of female urinary tract infections[62]. As for risankizumab, loss of consciousness\u0026nbsp;in female patients, and dizziness, and fall in male patients may be related to central nervous system or cardiovascular AEs[17,31]. In addition, women should be careful to stay hydrated while taking\u0026nbsp;risankizumab\u0026nbsp;to prevent dehydration, the mechanism of action remains unclear.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs for the occurrence median time AEs induced by ustekinumab/risankizumab in different sex groups, There were differences between men and women in the ustekinumab group, onset of AEs was 155.5 days, 200 days, respectively. Therefore, when men take ustekinumab, they should be concerned about AEs earlier.\u0026nbsp;The mechanism that causes the timing of AEs with ustekinumab to differ between genders is unclear. There was no significant difference in the occurrence time of AEs between risankizumab groups of different genders, both of them should be concerned about the occurrence of AEs in about 100 days.\u003c/p\u003e\n\u003cp\u003eOur study has several limitations, mainly associated with disproportionality analysis studies. Underreporting of adverse events occurs in spontaneous reporting systems, and not all AEs related to a particular drug are reported to the FDA. If a particular AE was not reported in a clinical trial program, the reporter may not attribute it to that drug. Due to the lack of a denominator, it was not possible to accurately calculate the incidence of specific AE. Besides‌, limitations of disproportionality analyses include limited detailed demographic data, risk factors, comorbidities, and duration of exposure compared to formal epidemiological studies. Another limitation is that most AEs in the FAERS database were reported by customers, especially risankizumab. Therefore, the quality of the reports can not be guaranteed. In addition, given the attention risankizumab has received following FDA approval for the treatment of CD, there may be the possibility of overreporting of AEs. Furthermore, the smaller number of risankizumab reports as compared to ustekinumab may limit generalization. Finally, all signal detection results can only indicate a statistical correlation; Whether causality really exists needs further evaluation and research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study investigated and analyzed AEs signals associated with ustekinumab and risankizumab based on the FAERS database to enhance clinical medication safety. The AEs identified in this study largely align with those documented in the ustekinumab’s and risankizumab's manual. Additionally, we uncovered AEs that were not previously listed, including clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab. These findings supplement the limited sample size of pre-market clinical studies. Gender-specific patients should be concerned about the occurrence of appropriate AEs when taking ustekinumab and risankizumab and our study provided evidence for ustekinumab and risankizumab in the treatment of CD. However, our study has limitations, we have not yet explored the correlation between ustekinumab-related/risankizumab-related AEs and the drug itself, underscoring the need to augment safety information. Further research is still warranted to elucidate the relationship between novel ustekinumab-related/risankizumab-related AEs and the drug and to refine ustekinumab and risankizumab’s safety profile.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003einhibits interleukin\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCrohn’s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAEs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eadverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eFAERS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnited States Food and Drug Administration Adverse Event Reporting System\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eROR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ereporting odds ratio\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePRR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eproportional reporting ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003econfidence interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eIBD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003einfammatory bowel disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSystem Organ Classes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eEthical approval and consent to participate was not required for this study because it used the FAERS database, which is a free open-access database.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article or Supplementary Materials, further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003ch2\u003eAuthor contributions\u003c/h2\u003e\n\u003cp\u003eAll named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, J.X., C.T., and Y.C. designed the research; J.X., C.T., performed the research; J.X. and L.X. collected and analyzed data; J.X. and C.T. wrote the manuscript; J.X., C.T., L.X., and Y.C. critically revised the paper; L.X. and Y.C. final approved of the version to be published. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1 Department of pharmacy, The First Affiliated Hospital of Army Medical University, Chongqing 400038, China.\u003c/p\u003e\n\u003cp\u003e2 Department of Pharmacy, Zigong Fourth People\u0026apos;s Hospital, Zigong, Sichuan 643000, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLightner AL, Vogel JD, Carmichael JC, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Crohn's Disease. 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Infect Dis Clin North Am. 2014;;28:1\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.idc.2013.09.003\u003c/span\u003e\u003cspan address=\"10.1016/j.idc.2013.09.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. :.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"FAERS, ustekinumab, risankizumab, IgG1 monoclonal antibody, adverse events, Crohn's disease","lastPublishedDoi":"10.21203/rs.3.rs-6189305/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6189305/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e \u003cb\u003eBackground\u003c/b\u003e Ustekinumab and risankizumab, humanized IgG1 monoclonal antibody that\u003c/p\u003e \u003cp\u003eselectively inhibits interleukin(IL)-23/IL-12 and IL-23, respectively, is currently approved for treating Crohn\u0026rsquo;s disease(CD). This study identified and characterized adverse events (AEs) significantly related to IgG1 monoclonal antibodies in treating CD and compared the differences between the two drugs to provide clinical reference.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e AEs reports were collected from the United States Food and Drug Administration Adverse Event Reporting System(FAERS). Ustekinumab\u0026rsquo;s AEs were collected from the third quarter of 2016 to the second quarter of 2024, while risankizumab\u0026rsquo;s AEs were collected from the second quarter of 2022 to the second quarter of 2024. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to assess the reporting of AEs induced by ustekinumab and risankizumab in treating CD. When the lower limit of the 95% confidence interval (CI) of ROR\u0026thinsp;\u0026gt;\u0026thinsp;1.0 and PRR\u0026thinsp;\u0026ge;\u0026thinsp;2 with an associated χ2 value of 4 or more was considered the threshold for a signal.\u003c/p\u003e \u003cp\u003e \u003cb\u003eResults\u003c/b\u003e A total of 2,5223 AE reports were retrieved from FAERS, with 1,9753 for ustekinumab, and 5470 for risankizumab. Reports for females were approximately 20% more than males, and patients aged 18-64.9 years reported the highest number of AEs. Interestingly, 50/77 PTs in at least 10 cases were classified as unexpected AEs, such as clostridium difficile infection, cellulitis, abdominal abscess, therapeutic response decreased, etc. for ustekinumab, and fall, intestinal obstruction, injection site haemorrh, loss of consciousnesss, etc. for risankizumab. There are similarities and differences in the presentation of ustekinumab-related and risankizumab-related AEs in males and females.\u003c/p\u003e \u003cp\u003e \u003cb\u003eConclusions\u003c/b\u003e Gender-specific patients should be concerned about the occurrence of appropriate AEs when taking medications for CD. Our study provided evidence for ustekinumab and risankizumab in the treatment of CD.\u003c/p\u003e","manuscriptTitle":"Risk factors for humanized IgG1 monoclonal antibody in the treatment of Crohn's disease: pharmacovigilance of the FDA adverse event reporting system (FAERS)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-12 09:53:48","doi":"10.21203/rs.3.rs-6189305/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e36f085f-87ac-42ea-a1c0-d7397439e39f","owner":[],"postedDate":"March 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-10T16:23:38+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-12 09:53:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6189305","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6189305","identity":"rs-6189305","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}