Vedolizumab adverse event profile: pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS)

Vedolizumab adverse event profile: pharmacovigilance study based on 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 Article Vedolizumab adverse event profile: pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS) Guanghui Yuan, Jie Liu, Yi Xu, Zhaowei Shan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6552177/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Objective: This study aims to assess the adverse event profile of Vedolizumab using FDA Adverse Event Reporting System (FAERS) data to identify potential safety risks and support clinical use. Methods: FAERS data from Q1 2014 to Q1 2024 were analyzed. Adverse drug events (ADEs) related to Vedolizumab were extracted and evaluated using four signal detection methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Results: Analysis included 50,852 reports identifying vedolizumab as the primary suspected drug. At the system organ class (SOC) level, it was significantly associated with gastrointestinal disorders, pregnancy-related conditions, infections, and procedural complications. Using all four algorithms, 103 adverse event (AE) signals were detected, with venous access complications, urgency of defecation, and fistulas being most common. Notable AEs absent from the drug label were also identified. Conclusion: This study underscores certain safety risks of Vedolizumab, particularly gastrointestinal reactions and infections, providing valuable evidence for clinical decision-making and future research. Biological sciences/Computational biology and bioinformatics Health sciences/Gastroenterology Vedolizumab pharmacovigilance adverse event FAERS Figures Figure 1 Key message The safety profile of vedolizumab, a gut-selective monoclonal antibody targeting α4β7 integrin, was previously characterized by clinical trials and drug labeling, which documented common adverse events (AEs) such as infections and myalgia. However, systematic evaluation of long-term or rare risks in real-world settings remained incomplete. This pharmacovigilance study, utilizing FDA Adverse Event Reporting System (FAERS) data, identified 103 significant AE signals, including previously unreported risks such as venous access complications, sclerosing cholangitis, and pregnancy-related adverse events (e.g., abnormal umbilical cord attachment), thereby addressing gaps in pharmacovigilance knowledge. These findings emphasize the necessity for intensified clinical surveillance of gastrointestinal, infectious, and perinatal risks, while providing robust evidence to update drug safety information and inform regulatory decision-making. Introduction Inflammatory bowel disease (IBD) is a chronic, immune-mediated disorder that affects the gastrointestinal tract and encompasses two major subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis (UC) is a primary, chronic inflammatory condition of the colonic mucosa, typically beginning in the rectum and often extending proximally in a continuous manner, affecting part or all of the colon [1] . Patients commonly present with symptoms such as hematochezia or rectal bleeding, observed in approximately 90% of cases [2] , in addition to other manifestations including abdominal pain, fatigue, and intestinal urgency, all of which significantly impair the quality of life [3] . Crohn's disease (CD), on the other hand, is a chronic inflammatory disorder of the gastrointestinal tract, which may lead to progressive intestinal damage and disability. It is characterized by chronic, recurrent transmural inflammation, which can result in symptoms such as persistent abdominal pain, diarrhea, bowel obstruction, and perianal lesions [4] . The pathogenesis of both UC and CD is multifactorial, involving genetic susceptibility, environmental triggers, immune dysregulation, dietary factors, and psychosocial influences. These complexities underscore the necessity for diverse and individualized treatment strategies, wherein the development of effective and safe pharmacological therapies becomes critical. Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin expressed on gut-homing lymphocytes, thereby modulating intestinal inflammation by restricting the recruitment of lymphocytes from the bloodstream into the intestinal lamina propria. This therapeutic agent was approved by the U.S. Food and Drug Administration (FDA) on May 20, 2014, for the treatment of adults with moderate-to-severe active ulcerative colitis (UC) and Crohn's disease (CD), and has since been widely adopted in clinical practice [5] . A meta-analysis indicated that approximately 60% of UC and CD patients, who had not previously received biologic therapy, achieved clinical remission by week 52 of Vedolizumab treatment. Furthermore, 40.1% of UC patients and 48.0% of CD patients achieved steroid-free clinical remission by week 14 [6] . Real-world data on Vedolizumab have identified myalgia and arthralgia as the most common adverse events, followed by nasopharyngitis, infections, and rash [7] . In the GEMINI I and II trials, 1434 patients with UC or CD were treated with 300 mg Vedolizumab for up to 52 weeks. Adverse events were reported in 52% of Vedolizumab-treated patients, compared to 45% in the placebo group, with severe adverse events occurring in 7% and 4% of patients, respectively [5] . A comprehensive and systematic collection and analysis of Vedolizumab-related adverse drug reactions are essential for the early identification of potential adverse effects and the optimization of therapeutic regimens. The U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) includes adverse drug event (ADE) report data submitted by healthcare professionals, pharmaceutical manufacturers, patients, and other individuals from various regions. This database, which has been publicly available since 2004, is updated quarterly and is widely recognized by international scholars for its vast scale and standardized structure. The present study aims to leverage FAERS data to explore and perform statistical analysis of real-world adverse drug reactions (ADRs) associated with Vedolizumab since its market approval. The goal is to provide valuable insights that may help mitigate adverse reactions and guide the rational use of Vedolizumab in clinical practice. Methods Data Source This retrospective pharmacovigilance analysis utilized the FAERS database. Given the approval timeline of Vedolizumab, we collected ADE report data related to Vedolizumab spanning from the first quarter of 2014 to the first quarter of 2024, covering a total of 41 quarters. The data were downloaded in ASCII format and included seven key datasets: 1) DEMO: Demographic and administrative information, along with individual records for each event report; 2) DRUG: Information about drugs/biologics mentioned in the case reports; 3) REAC: Information on adverse drug reactions; 4) OUTC: Patient outcome data; 5) RPSR: Source of the report for each event; 6) THER: Start and end dates of the drug therapy associated with the reported event; 7) INDI: Indications for the drug administration. Data Acquisition and Preprocessing In this study, all data downloaded from the FDA website were imported into MySQL 8.0 for preprocessing. A total of 15,362,342 reports were initially obtained from the FAERS database, which were then processed to eliminate duplicates in order to enhance the reliability of the results. As outlined in the README file accompanying each quarterly data package, duplicates were identified and removed based on the "CASEID," in line with FDA_AERS guidelines. The most recent FDA_DT within the same CASEID series was prioritized, and when both CASEID and FDA_DT were identical, the PRIMARYID was used as the filtering criterion. After de-duplication, the number of reports was reduced to 13,045,652 (Fig. 1). Additionally, drug names were standardized using Medex_UIMA_1.3.8, while adverse events (AEs) in the FAERS database were categorized and described using the preferred terms (PT) and system organ class (SOC) terms from the latest version of the MedDRA (26.1). Since the FAERS database includes reports for all FDA-approved drugs, we utilized IBM Micromedex as a reference dictionary, retrieving relevant reports for the drug "Vedolizumab" using its generic name and brand name "Entyvio." Data Mining and Analysis In pharmacovigilance research, disproportionality analysis is a key method for identifying and detecting drug-related adverse reaction signals. This approach involves comparing the frequency ratios observed in the exposed and non-exposed populations using a 2x2 contingency table to assess the strength of association between a drug and an adverse event. In this study, commonly used disproportionality metrics such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM) were employed concurrently to detect ADE signals. This strategy allows for cross-validation, reduction of bias, and identification of rare adverse events. All calculations were based on the 2x2 contingency table method, with detailed equations and criteria provided in the supplementary Table (S1). An ADE signal was considered detected when the incidence rate for the selected drug's adverse event was significantly higher than the background frequency and met the criteria of all four algorithms. The higher the value, the stronger the signal, indicating a stronger association between the drug and the adverse event. Serious adverse reactions were defined as those leading to hospitalization, disability, death, or life-threatening conditions. Data processing and statistical analyses were performed using MySQL 8.0, Microsoft Excel 2021, and GraphPad Prism 10. Results Fundamental Characteristics Between the first quarter of 2014 and the first quarter of 2024, a total of 13,045,652 reports were included in the FAERS database after excluding duplicate event reports. These reports encompassed 37,214,775 distinct adverse drug reactions. Notably, we selected reports where Vedolizumab was identified as the primary suspected drug (PS), resulting in 50,852 reports that documented 183,083 individual adverse events. A descriptive analysis of the clinical characteristics associated with Vedolizumab-related events is summarized in Table 1. Since its market approval, the number of adverse event (AE) reports associated with Vedolizumab has steadily increased, reaching a total of 12,143 reports across the four quarters of 2023. Regarding gender distribution, the majority of reports included gender information, with a slight predominance of female patients (51.94%) over male patients (41.58%), though the difference was not statistically significant. In terms of age, patients aged between 18 and 65 years represented the largest cohort, comprising 46.93% (23,861 reports), with a median age of 49 years. Geographically, Canada submitted the highest number of reports, totaling 22,571 (44.39%), followed by the United States at 30.36%. Detailed global distribution is presented in Supplementary Figure 1. In terms of report sources, consumers and healthcare professionals were the primary reporters, contributing 54.21% and 29.87% of the total, respectively, with pharmacists (11.70%) and other healthcare professionals (3.56%) following. Notably, 16 reports originated from legal representatives. Regarding outcomes of adverse events, the majority of AE reports were classified as "other serious" (67.40%), which somewhat hindered in-depth analysis of the event outcomes. In reports where outcomes were clearly specified, the most common result was hospitalization (27.65%, 14,862 cases), followed by death (3.44%, 1,848 cases), life-threatening conditions (0.68%, 364 cases), and disability (0.63%, 338 cases). Furthermore, although less frequent, 28 reports indicated outcomes requiring intervention to prevent permanent damage, an important consideration. Concerning indications, ulcerative colitis (22,751 reports, 45.0%) and Crohn's disease (20,306 reports, 40.1%) were the most commonly reported indications, consistent with the approved indications by the U.S. Food and Drug Administration (FDA). Other notable indications, aside from those with unknown causes, included inflammatory bowel disease (1,016 reports, 2.0%) and colitis (412 reports, 0.8%). Signal Detection for Vedolizumab Through disproportionality analysis, we identified 24 system organ classes (SOCs) associated with adverse events related to Vedolizumab. Table 2 presents the signal strength and report counts for Vedolizumab across various SOCs. The analysis revealed that, according to at least one of the four analytical methods used, the following SOCs were significantly identified: gastrointestinal disorders (n=51,657, ROR 4.17, PRR 3.28, IC 1.7, EBGM 3.24), pregnancy, puerperium, and perinatal conditions (n=1,772, ROR 2.38, PRR 2.36, IC 1.23, EBGM 2.35), infections and infestations (n=15,804, ROR 1.59, PRR 1.54, IC 0.62, EBGM 1.54), and injury, poisoning and procedural complications (n=25,254, ROR 1.29, PRR 1.25, IC 0.32, EBGM 1.25). These findings highlight the specific organ systems most commonly reported as adversely affected by Vedolizumab. However, they appear inconsistent with the information provided in the drug’s prescribing information and previously published clinical studies. Specifically, while the prescribing information similarly acknowledges gastrointestinal disorders and infections and infestations as common affected systems, it also lists general disorders and administration site conditions, but fails to mention pregnancy, puerperium, and perinatal conditions. Additionally, other common organ systems listed in the prescribing information, such as nervous system disorders, vascular diseases, respiratory, thoracic, and mediastinal diseases, musculoskeletal and connective tissue diseases, and skin and subcutaneous tissue disorders, did not meet the criteria for significance in any of the analytical methods employed. After meeting the criteria of all four analytical algorithms, we further identified 103 Vedolizumab-induced adverse event (AE) signals across the 24 system organ classes (SOCs). Table 3 presents the preferred terms (PTs) with at least 100 reports, with all PTs listed in Supplementary Table S2. To mitigate bias due to indications, we excluded PTs related to Vedolizumab’s approved indications (ulcerative colitis, Crohn’s disease, hematochezia, increased bowel frequency, and mucous stools). Even after this exclusion, 22 PTs and 8 corresponding SOCs remained. Among the most frequently reported AEs in our study were poor venous access (728 cases), defaecation urgency (698 cases), and fistulas (406 cases). Other notable AEs included faeces soft , anal abscess, gastrointestinal inflammation, intestinal stenosis, anal fistula, faecal calprotectin increased, proctalgia, anal fissure, abscess intestinal , dyschezia, large intestinal stenosis, sclerosing cholangitis, rectal absces, ileal stenosis, and proctitis. These reports were predominantly centered around gastrointestinal disorders, with only anal abscess and defecation difficulties explicitly recorded in the Vedolizumab prescribing information. Importantly, our data mining revealed several significant AEs not explicitly mentioned in the drug’s prescribing information, including gastrointestinal precancerous lesions (11 cases), abnormal umbilical cord attachment (4 cases), cholangitis sclerosing (115 cases), neurogenic shock (31 cases), colorectal adenoma (13 cases), neoplasm of appendix (6 cases), endocrine neoplasm (3 cases), intestinal adenocarcinoma (7 cases), and abdominal hernia obstructive (5 cases). As the reports collected in the FAERS database are submitted by a wide range of healthcare professionals, the analysis also revealed several signals unrelated to the drug. These signals were primarily concentrated in the categories of general disorders and administration site conditions, as well as pregnancy, puerperium, and perinatal conditions. The preferred terms (PTs) associated with these signals included therapeutic reaction time decreased, pregnancy, loss of therapeutic response, and drug level decreased, among others. Further details can be found in Table 3. Discussion Gastrointestinal System-Related Adverse Drug Events (ADEs) In our study, after excluding PTs related to the approved indications, the five most commonly reported ADEs within gastrointestinal disorders were defaecation urgency, soft stools, gastrointestinal inflammation, intestinal stenosis, and anal fistula. Notably, among these ADEs, only anal fissures and defecation difficulties were consistent with the drug's prescribing information. In contrast, other adverse events such as urgent defecation urges and anal fistula were not explicitly mentioned in the Vedolizumab prescribing information. It is currently unclear whether these symptoms represent manifestations of the underlying disease or are possibly drug-induced. On one hand, urgent defecation urges and soft stools are common in the disease course of UC and CD. Furthermore, studies have reported that the development of intestinal stenosis is a frequent complication of CD [8, 9] , affecting the entire gastrointestinal tract, with approximately 10% of CD patients experiencing colonic stenosis—2 to 3 times more common than ileal stenosis [8, 9] . It is less common, but colonic stenosis may also be observed in UC patients. On the other hand, considering the gut-selective mechanism of action of Vedolizumab, the increased risk of certain gastrointestinal disorders appears plausible. Pregnancy and Perinatal-Related ADEs Of particular interest is the identification of pregnancy and perinatal-related ADEs within the algorithm-derived SOC, with specific PTs including pregnancy and abnormal umbilical cord attachment. However, the lack of information regarding pregnancy outcomes limits further investigation into the risks of Vedolizumab use during pregnancy and the perinatal period for both the mother and fetus. Evidence from clinical trials suggests that among four studies using Vedolizumab, the incidence of early pregnancy loss was 18% (ranging from 12% to 24%) [10-13] , and the incidence of preterm birth was 19% (ranging from 12% to 26%) [10-13] . Compared to TNF inhibitors, Vedolizumab-exposed patients showed significantly higher rates of preterm birth, which supports and complements our findings, reinforcing the reliability of our results. Interestingly, four cases of abnormal umbilical cord attachment were reported. As a novel and potentially significant PT, we cannot definitively determine whether these cases were drug- or disease-related. Although no direct evidence currently links Vedolizumab to abnormal umbilical cord attachment, the drug’s mechanism of action—binding to α4β7 integrin to block lymphocyte migration—suggests that abnormal immune responses induced by either the drug or the disease could potentially affect fetal growth and the normal function of the umbilical cord. Clinicians should remain vigilant regarding the potential for pregnancy-related adverse events associated with Vedolizumab. Infection and Infestation-Related ADEs Infection and infestation-related ADEs primarily involved abscesses, with additional PTs of intestinal abscess and stoma site abscess identified, which were not mentioned in the prescribing information, while anal abscesses were consistent with the listed PTs. Key findings from the Vedolizumab GEMIMI trials indicated that severe infections were more common in Crohn’s disease (CD) patients than in those with ulcerative colitis (UC) [14-16] . Abscesses are the most frequently observed severe adverse event in CD patients, typically occurring in the anus, rectum, or perirectal region [14-16] , which aligns with our study's results. It is important to note that patients receiving placebo had a higher incidence of abscesses than those treated with Vedolizumab, suggesting that abscesses may be a complication of inflammatory bowel disease (IBD) rather than being specifically related to Vedolizumab. However, some subsequent studies also found contradictory results, with a higher rate of abscesses observed in the Vedolizumab group compared to the control group [14-16] . Moreover, other intestinal infections induced by Vedolizumab were rare in our findings, with only a small number of cases reporting gastrointestinal bacterial infections, Escherichia coli gastroenteritis, amoebic infections, and other perianal infections (Supplementary Table S2). The drug’s immunosuppressive action in the gut, mediated by binding to α4β7 integrin expressed on gut-homing lymphocytes, is a likely mechanism contributing to the increased risk of intestinal infections and infestations. Clinical trials have also indicated that Clostridium difficile and cytomegalovirus infections were exclusively observed in the Vedolizumab group [14-16] , thus highlighting the need for further cohort studies to evaluate the risks of gut and other infections. Stoma site abscesses typically occur as postoperative complications, and a cohort study focused solely on UC patients, which included 88 Vedolizumab-treated patients and 62 patients receiving anti-TNFα therapy within 12 weeks post-surgery, found that more Vedolizumab-treated patients developed superficial surgical site infections (p = 0.047) and ileostomy site skin-mucosa separation (p = 0.047) [17] . Hepatobiliary System-Related ADEs Interestingly, the results of this study reveal that sclerosing cholangitis is the most common ADE associated with the hepatobiliary system, yet it is not explicitly mentioned in the drug’s prescribing information. Multiple studies have indicated that Vedolizumab’s specific targeting of the gut-homing pathway (i.e., the interaction between α4β7 and its ligand MAdCAM-1) is implicated in the pathophysiology of sclerosing cholangitis [18] . Activated T cells homing from the gut to the liver may contribute to cholangitis associated with sclerosing cholangitis by upregulating the adhesion molecule MAdCAM-1 and the chemokine CCL, which could facilitate the recruitment of α4β7 integrin-positive T cells into the biliary endothelial cells [19, 20] . Therefore, Vedolizumab may play a role in reducing lymphocytic infiltration into the liver in patients with sclerosing cholangitis, thereby mitigating liver and biliary tract inflammation. Surprisingly, a GETAID multicenter cohort study that included 75 patients with sclerosing cholangitis and active IBD observed that, among 54 patients, 4 [7%] and 4 [11%] exhibited a reduction of at least 50% in serum alkaline phosphatase (ALP) levels from baseline to week 30 and week 54, respectively. However, no significant changes were observed in serum liver enzyme levels at either week 30 or week 54 compared to baseline. Overall, liver function tests did not show improvement, suggesting that Vedolizumab is ineffective in treating sclerosing cholangitis [21] . Epidemiological studies on sclerosing cholangitis and IBD demonstrate that they often co-occur, with similar geographic prevalence patterns, and that IBD is present in the majority of sclerosing cholangitis patients [22] . Therefore, it is difficult to determine whether sclerosing cholangitis is a symptom of the underlying disease or an adverse drug reaction induced by Vedolizumab. Conclusions In summary, this study provides evidence for the safety evaluation of Vedolizumab through multidimensional and multilevel analysis. Notably, although some adverse events (AEs), such as abnormal umbilical cord attachment, occur at a relatively low frequency, their high signal strength warrants further attention and investigation. Moreover, the study identified several notable adverse reactions not mentioned in the drug’s prescribing information, such as anal fistula, intestinal abscess, and sclerosing cholangitis. This underscores the importance for healthcare professionals to closely monitor the occurrence of adverse events in clinical practice to enable timely intervention. To obtain a more comprehensive and precise understanding, future research should adopt more rigorous prospective study designs, combining clinical trials with epidemiological studies, with the goal of more accurately assessing the safety risks associated with Vedolizumab. Abbreviations FAERS: the FDA Adverse Event Reporting System ADEs: Adverse drug events ROR: Reporting Odds Ratio PRR: Proportional Reporting Ratio BCPNN: Bayesian Confidence Propagation Neural Network EBGM: Empirical Bayesian Geometric Mean SOC: system organ class Declarations Data availability statement The original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author. Funding No funds were received to support this study. Conflict of interest The authors declare that there are no relevant financial or non-financial interests to be disclosed. Author contributions Material preparation, data collection and analysis were performed by Guanghui Yuan and Jie Liu. Yi Xu and Zhaowei Shan was responsible for research design.The first draft of the manuscript was written by Guanghui Yuan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. All authors contributed to this article and approved the submitted version. References ORDAS I, ECKMANN L, TALAMINI M, et al. Ulcerative colitis[J]. Lancet, 2012,380(9853): 1606-1619. Le BERRE C, HONAP S, PEYRIN-BIROULET L. Ulcerative colitis[J]. Lancet, 2023,402(10401): 571-584. MCCOUBREY L E, SEEGOBIN N, SANGFUANG N, et al. The colon targeting efficacies of mesalazine medications and their impacts on the gut microbiome[J]. J Control Release, 2024,369: 630-641. TORRES J, MEHANDRU S, COLOMBEL J F, et al. Crohn's disease[J]. Lancet, 2017,389(10080): 1741-1755. POOLE R M. Vedolizumab: first global approval[J]. Drugs, 2014,74(11): 1293-1303. ATTAUABI M, MADSEN G R, BENDTSEN F, et al. Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn's disease - a systematic review with meta-analysis[J]. Dig Liver Dis, 2022,54(9): 1168-1178. ENGEL T, UNGAR B, YUNG D E, et al. Vedolizumab in IBD-Lessons From Real-world Experience; A Systematic Review and Pooled Analysis[J]. J Crohns Colitis, 2018,12(2): 245-257. LOUIS E, COLLARD A, OGER A F, et al. Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease[J]. Gut, 2001,49(6): 777-782. COSNES J, CATTAN S, BLAIN A, et al. Long-term evolution of disease behavior of Crohn's disease[J]. Inflamm Bowel Dis, 2002,8(4): 244-250. BAR-GIL S A, BEN Y A, LIVOVSKY D M, et al. Exposure to Vedolizumab in IBD Pregnant Women Appears of Low Risk for Mother and Neonate: A First Prospective Comparison Study[J]. Am J Gastroenterol, 2019,114(7): 1172-1175. MAHADEVAN U, VERMEIRE S, LASCH K, et al. Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2017,45(7): 941-950. MOENS A, van HOEVE K, HUMBLET E, et al. Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab[J]. J Crohns Colitis, 2019,13(1): 12-18. MOENS A, van der WOUDE C J, JULSGAARD M, et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study[J]. Aliment Pharmacol Ther, 2020,51(1): 129-138. FEAGAN B G, RUTGEERTS P, SANDS B E, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis[J]. N Engl J Med, 2013,369(8): 699-710. SANDBORN W J, FEAGAN B G, RUTGEERTS P, et al. Vedolizumab as induction and maintenance therapy for Crohn's disease[J]. N Engl J Med, 2013,369(8): 711-721. COLOMBEL J F, SANDS B E, RUTGEERTS P, et al. The safety of vedolizumab for ulcerative colitis and Crohn's disease[J]. Gut, 2017,66(5): 839-851. LIGHTNER A L, RAFFALS L E, MATHIS K L, et al. Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease[J]. J Crohns Colitis, 2017,11(2): 185-190. EKSTEEN B, GRANT A J, MILES A, et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis[J]. J Exp Med, 2004,200(11): 1511-1517. BURAK K, ANGULO P, PASHA T M, et al. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis[J]. Am J Gastroenterol, 2004,99(3): 523-526. EKSTEEN B, MORA J R, HAUGHTON E L, et al. Gut homing receptors on CD8 T cells are retinoic acid dependent and not maintained by liver dendritic or stellate cells[J]. Gastroenterology, 2009,137(1): 320-329. CARON B, PEYRIN-BIROULET L, PARIENTE B, et al. Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study[J]. J Crohns Colitis, 2019,13(10): 1239-1247. van MUNSTER K N, BERGQUIST A, PONSIOEN C Y. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?[J]. J Hepatol, 2024,80(1): 155-168. Tables Table 1 Characteristics Case number Case proportion, % Year 2014 9 0.18 2015 1346 2.65 2016 2194 4.31 2017 2437 4.79 2018 3381 6.65 2019 4001 7.87 2020 4574 8.99 2021 7444 14.64 2022 7817 15.37 2023 12143 23.88 2024 5424 10.67 Gender female 26410 51.94 male 21144 41.58 unknown 3298 6.49 Age_yr 49 Age_yrQ =75 2939 5.78 unknow 18291 35.97 wt 69.60(58.00,84.35) Reporter Consumer 27568 54.21 Physician 15191 29.87 Pharmacist 5950 11.7 Other health-professional 1809 3.56 unknown 318 0.63 Lawyer 16 0.03 Reported countries Canada 22571 44.39 United States 15440 30.36 United Kingdom 2053 4.04 Australia 2042 4.02 Germany 1053 2.07 Japan 1035 2.04 Route intravenous 41775 82.15 other 6822 13.42 subcutaneous 1389 2.73 intravenous drip 722 1.42 transmammary 54 0.11 Outcomes other serious 3622 67.4 hospitalization 14862 27.65 death 1848 3.44 life threatening 364 0.68 disability 338 0.63 congenital anomaly 80 0.15 required intervention to Prevent Permanent Impairment/Damage 28 0.05 Table 2 SOC Case Reports ROR(95% CI) PRR(95% CI) chisq IC(IC025) EBGM(EBGM05) gastrointestinal disorders 51657 4.17(4.13, 4.21) 3.28(3.28, 3.28) 88030.41 1.7(1.68) 3.24(3.21) pregnancy, puerperium and perinatal conditions 1772 2.38(2.27, 2.49) 2.36(2.27, 2.45) 1384.58 1.23(1.16) 2.35(2.26) infections and infestations 15804 1.59(1.57, 1.62) 1.54(1.51, 1.57) 3156.12 0.62(0.6) 1.54(1.52) injury, poisoning and procedural complications 25254 1.29(1.27, 1.31) 1.25(1.23, 1.27) 1417.49 0.32(0.3) 1.25(1.24) investigations 9460 0.84(0.82, 0.86) 0.85(0.83, 0.87) 272.56 -0.24(-0.27) 0.85(0.83) musculoskeletal and connective tissue disorders 8425 0.83(0.82, 0.85) 0.84(0.82, 0.86) 265.21 -0.25(-0.28) 0.84(0.83) general disorders and administration site conditions 29074 0.82(0.81, 0.83) 0.85(0.83, 0.87) 929.28 -0.23(-0.25) 0.85(0.84) hepatobiliary disorders 1228 0.78(0.74, 0.83) 0.79(0.74, 0.84) 71.55 -0.35(-0.43) 0.79(0.75) vascular disorders 2875 0.75(0.73, 0.78) 0.76(0.73, 0.79) 228.82 -0.4(-0.45) 0.76(0.73) ear and labyrinth disorders 585 0.7(0.64, 0.76) 0.7(0.65, 0.76) 75.15 -0.51(-0.63) 0.7(0.66) metabolism and nutrition disorders 2506 0.63(0.61, 0.66) 0.64(0.62, 0.67) 529.09 -0.65(-0.71) 0.64(0.62) respiratory, thoracic and mediastinal disorders 5728 0.63(0.62, 0.65) 0.64(0.63, 0.65) 1188.3 -0.63(-0.67) 0.64(0.63) nervous system disorders 8406 0.53(0.52, 0.54) 0.55(0.54, 0.56) 3373.56 -0.86(-0.89) 0.55(0.54) eye disorders 1971 0.52(0.5, 0.54) 0.52(0.5, 0.54) 863.21 -0.93(-0.99) 0.53(0.51) reproductive system and breast disorders 734 0.5(0.46, 0.54) 0.5(0.46, 0.54) 367.74 -0.99(-1.1) 0.5(0.47) neoplasms benign, malignant and unspecified 2874 0.5(0.48, 0.51) 0.5(0.48, 0.52) 1448.69 -0.99(-1.04) 0.5(0.49) endocrine disorders 240 0.49(0.43, 0.56) 0.49(0.44, 0.55) 127.11 -1.02(-1.21) 0.49(0.44) skin and subcutaneous tissue disorders 5116 0.46(0.45, 0.48) 0.48(0.47, 0.49) 3081.45 -1.06(-1.1) 0.48(0.47) renal and urinary disorders 1737 0.46(0.44, 0.49) 0.47(0.45, 0.49) 1068.58 -1.09(-1.16) 0.47(0.45) cardiac disorders 1822 0.42(0.4, 0.44) 0.43(0.41, 0.45) 1446.21 -1.23(-1.3) 0.43(0.41) immune system disorders 858 0.37(0.35, 0.4) 0.38(0.36, 0.4) 888.71 -1.4(-1.5) 0.38(0.36) blood and lymphatic system disorders 1109 0.35(0.33, 0.37) 0.35(0.33, 0.37) 1326.89 -1.49(-1.58) 0.36(0.34) psychiatric disorders 3666 0.34(0.33, 0.35) 0.35(0.34, 0.36) 4611.39 -1.5(-1.55) 0.35(0.34) congenital, familial and genetic disorders 182 0.33(0.29, 0.39) 0.33(0.29, 0.38) 241.74 -1.58(-1.79) 0.34(0.3) Table 3 SOC PTs Case Reports ROR(95% CI) PRR(95% CI) chisq IC(IC025) EBGM(EBGM05) gastrointestinal disorders colitis ulcerative 8819 99.81(97.27, 102.41) 95.05(93.21, 96.93) 558741.4 6.02(5.99) 64.98(63.6) gastrointestinal disorders crohn's disease 6678 40.71(39.64, 41.81) 39.26(38.5, 40.04) 208754.81 5.05(5.01) 33.04(32.31) gastrointestinal disorders haematochezia 3169 19.92(19.2, 20.67) 19.59(18.84, 20.37) 51023.67 4.17(4.11) 17.95(17.41) gastrointestinal disorders frequent bowel movements 2445 33.24(31.84, 34.7) 32.81(31.55, 34.12) 64903.01 4.83(4.76) 28.37(27.36) general disorders and administration site conditions therapeutic reaction time decreased 1758 1734.45(1501.69, 2003.29) 1717.81(1497.58, 1970.43) 317773.64 7.51(7.41) 181.85(161.2) pregnancy, puerperium and perinatal conditions pregnancy 1189 31.25(29.39, 33.22) 31.05(29.28, 32.93) 29985.75 4.76(4.67) 27.05(25.7) gastrointestinal disorders mucous stools 738 59.9(55.17, 65.03) 59.66(55.16, 64.53) 32873.74 5.53(5.42) 46.3(43.22) vascular disorders poor venous access 728 26.31(24.35, 28.43) 26.21(24.23, 28.35) 15630.56 4.54(4.43) 23.32(21.86) investigations drug level decreased 707 23.2(21.46, 25.08) 23.11(21.37, 24.99) 13426.32 4.38(4.27) 20.85(19.53) gastrointestinal disorders defaecation urgency 698 39.72(36.62, 43.08) 39.57(36.59, 42.8) 21949.87 5.06(4.94) 33.26(31.07) general disorders and administration site conditions loss of therapeutic response 613 132.63(119.78, 146.85) 132.19(119.85, 145.8) 48267.72 6.33(6.19) 80.34(73.77) musculoskeletal and connective tissue disorders fistula 406 13.04(11.79, 14.42) 13.01(11.8, 14.35) 4230.82 3.62(3.47) 12.29(11.3) gastrointestinal disorders faeces soft 366 15.18(13.65, 16.88) 15.15(13.74, 16.71) 4500.1 3.82(3.67) 14.16(12.96) infections and infestations anal abscess 352 21.85(19.58, 24.4) 21.81(19.39, 24.53) 6310.5 4.31(4.15) 19.79(18.05) gastrointestinal disorders gastrointestinal inflammation 342 14(12.54, 15.62) 13.97(12.42, 15.71) 3853.31 3.72(3.56) 13.13(11.98) gastrointestinal disorders intestinal stenosis 298 25.22(22.35, 28.45) 25.18(22.39, 28.32) 6153.36 4.49(4.32) 22.5(20.34) gastrointestinal disorders anal fistula 289 18.66(16.54, 21.05) 18.63(16.56, 20.95) 4416.35 4.1(3.93) 17.15(15.5) investigations faecal calprotectin increased 238 23.04(20.15, 26.35) 23.01(20.06, 26.39) 4499.45 4.38(4.18) 20.76(18.56) gastrointestinal disorders proctalgia 222 12.71(11.09, 14.55) 12.69(11.06, 14.56) 2250.11 3.59(3.39) 12(10.71) gastrointestinal disorders anal fissure 208 13.48(11.72, 15.51) 13.47(11.74, 15.45) 2250.97 3.67(3.46) 12.69(11.28) infections and infestations abscess intestinal 131 22.51(18.79, 26.96) 22.49(18.85, 26.83) 2421.27 4.35(4.09) 20.34(17.49) gastrointestinal disorders dyschezia 131 12.82(10.75, 15.3) 12.81(10.74, 15.28) 1341.8 3.6(3.34) 12.11(10.45) gastrointestinal disorders large intestinal stenosis 127 20.78(17.31, 24.95) 20.77(17.41, 24.78) 2167.04 4.24(3.98) 18.93(16.24) hepatobiliary disorders cholangitis sclerosing 115 19.16(15.82, 23.19) 19.14(15.73, 23.28) 1806.71 4.14(3.86) 17.58(14.98) infections and infestations rectal abscess 109 22.7(18.62, 27.67) 22.68(18.64, 27.59) 2031.43 4.36(4.07) 20.5(17.37) gastrointestinal disorders ileal stenosis 103 23.29(18.99, 28.56) 23.28(19.14, 28.32) 1969.43 4.39(4.1) 20.98(17.69) gastrointestinal disorders proctitis 100 12.54(10.24, 15.35) 12.53(10.3, 15.24) 999.32 3.57(3.28) 11.86(10.01) Additional Declarations No competing interests reported. Supplementary Files supplementaryTableS1..docx SupplementaryTableS2.xlsx SupplementaryFigure1.tif Cite Share Download PDF Status: Published Journal Publication published 28 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 08 Aug, 2025 Reviewers agreed at journal 22 Jul, 2025 Reviews received at journal 16 Jul, 2025 Reviews received at journal 10 Jul, 2025 Reviews received at journal 10 Jul, 2025 Reviewers agreed at journal 09 Jul, 2025 Reviewers agreed at journal 09 Jul, 2025 Reviewers agreed at journal 09 Jul, 2025 Reviewers invited by journal 09 Jul, 2025 Editor invited by journal 22 May, 2025 Editor assigned by journal 22 May, 2025 Submission checks completed at journal 04 May, 2025 First submitted to journal 04 May, 2025 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. 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University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Liu","suffix":""},{"id":483721946,"identity":"57b33ab6-ff0a-422a-9c98-92d807824899","order_by":2,"name":"Yi Xu","email":"","orcid":"","institution":"The affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Xu","suffix":""},{"id":483721949,"identity":"11e18694-bfbe-44c4-94ac-699ceb084f5f","order_by":3,"name":"Zhaowei Shan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIie3Rv0vEMBTA8ZTCTa8GtxTOX/9BoIMIRf+VFw7icqDjjYGDTgeu1z9C6OT8StZg18ItFcFR2kWcRG+4SUxWh3zH5H0ISRiLxf5lwNpxJU5n3KgBoQTOTZAkVriy4IJe5TDX83xLQZJSVmlVG/V2PJS2lAb9QHaPRMJZ1ZDVDJcdSEbJOC09pH9Hul/ZorGVHtDt4DI1aV4/+YiT+1NOGnK3Um12cGVolmYhklU2aejuQ6ivZ5CEAdJt9kRf1Aa1QKAwyXuQh0deSIQF5Nt27b3LUeeK6fCVL59wfcP5uh0nDznv8ddaYv6e/+nsgbz7sVgsFmPsGzGdZSuwgur7AAAAAElFTkSuQmCC","orcid":"","institution":"The affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Zhaowei","middleName":"","lastName":"Shan","suffix":""}],"badges":[],"createdAt":"2025-04-29 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12:26:40","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":27096,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6552177/v1/e2e18ef45baf9cc038313683.xlsx"},{"id":86508585,"identity":"21aad603-d878-4025-b7ac-f23c4a6d513e","added_by":"auto","created_at":"2025-07-11 12:26:40","extension":"tif","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":6704814,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFigure1.tif","url":"https://assets-eu.researchsquare.com/files/rs-6552177/v1/5ced20fe24262447346293e2.tif"}],"financialInterests":"No competing interests reported.","formattedTitle":"Vedolizumab adverse event profile: pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS)","fulltext":[{"header":"Key message","content":"\u003cp\u003eThe safety profile of vedolizumab, a gut-selective monoclonal antibody targeting α4β7 integrin, was previously characterized by clinical trials and drug labeling, which documented common adverse events (AEs) such as infections and myalgia. However, systematic evaluation of long-term or rare risks in real-world settings remained incomplete. This pharmacovigilance study, utilizing FDA Adverse Event Reporting System (FAERS) data, identified 103 significant AE signals, including previously unreported risks such as venous access complications, sclerosing cholangitis, and pregnancy-related adverse events (e.g., abnormal umbilical cord attachment), thereby addressing gaps in pharmacovigilance knowledge. These findings emphasize the necessity for intensified clinical surveillance of gastrointestinal, infectious, and perinatal risks, while providing robust evidence to update drug safety information and inform regulatory decision-making.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eInflammatory bowel disease (IBD) is a chronic, immune-mediated disorder that affects the gastrointestinal tract and encompasses two major subtypes: ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis (UC) is a primary, chronic inflammatory condition of the colonic mucosa, typically beginning in the rectum and often extending proximally in a continuous manner, affecting part or all of the colon\u003csup\u003e[1]\u003c/sup\u003e. Patients commonly present with symptoms such as hematochezia or rectal bleeding, observed in approximately 90% of cases\u003csup\u003e[2]\u003c/sup\u003e, in addition to other manifestations including abdominal pain, fatigue, and intestinal urgency, all of which significantly impair the quality of life\u003csup\u003e[3]\u003c/sup\u003e. Crohn's disease (CD), on the other hand, is a chronic inflammatory disorder of the gastrointestinal tract, which may lead to progressive intestinal damage and disability. It is characterized by chronic, recurrent transmural inflammation, which can result in symptoms such as persistent abdominal pain, diarrhea, bowel obstruction, and perianal lesions\u003csup\u003e[4]\u003c/sup\u003e. The pathogenesis of both UC and CD is multifactorial, involving genetic susceptibility, environmental triggers, immune dysregulation, dietary factors, and psychosocial influences. These complexities underscore the necessity for diverse and individualized treatment strategies, wherein the development of effective and safe pharmacological therapies becomes critical.\u003c/p\u003e\u003cp\u003eVedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin expressed on gut-homing lymphocytes, thereby modulating intestinal inflammation by restricting the recruitment of lymphocytes from the bloodstream into the intestinal lamina propria. This therapeutic agent was approved by the U.S. Food and Drug Administration (FDA) on May 20, 2014, for the treatment of adults with moderate-to-severe active ulcerative colitis (UC) and Crohn's disease (CD), and has since been widely adopted in clinical practice\u003csup\u003e[5]\u003c/sup\u003e. A meta-analysis indicated that approximately 60% of UC and CD patients, who had not previously received biologic therapy, achieved clinical remission by week 52 of Vedolizumab treatment. Furthermore, 40.1% of UC patients and 48.0% of CD patients achieved steroid-free clinical remission by week 14\u003csup\u003e[6]\u003c/sup\u003e. Real-world data on Vedolizumab have identified myalgia and arthralgia as the most common adverse events, followed by nasopharyngitis, infections, and rash \u003csup\u003e[7]\u003c/sup\u003e. In the GEMINI I and II trials, 1434 patients with UC or CD were treated with 300 mg Vedolizumab for up to 52 weeks. Adverse events were reported in 52% of Vedolizumab-treated patients, compared to 45% in the placebo group, with severe adverse events occurring in 7% and 4% of patients, respectively\u003csup\u003e[5]\u003c/sup\u003e. A comprehensive and systematic collection and analysis of Vedolizumab-related adverse drug reactions are essential for the early identification of potential adverse effects and the optimization of therapeutic regimens.\u003c/p\u003e\u003cp\u003eThe U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) includes adverse drug event (ADE) report data submitted by healthcare professionals, pharmaceutical manufacturers, patients, and other individuals from various regions. This database, which has been publicly available since 2004, is updated quarterly and is widely recognized by international scholars for its vast scale and standardized structure. The present study aims to leverage FAERS data to explore and perform statistical analysis of real-world adverse drug reactions (ADRs) associated with Vedolizumab since its market approval. The goal is to provide valuable insights that may help mitigate adverse reactions and guide the rational use of Vedolizumab in clinical practice.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData Source\u003c/h2\u003e\u003cp\u003eThis retrospective pharmacovigilance analysis utilized the FAERS database. Given the approval timeline of Vedolizumab, we collected ADE report data related to Vedolizumab spanning from the first quarter of 2014 to the first quarter of 2024, covering a total of 41 quarters. The data were downloaded in ASCII format and included seven key datasets: 1) DEMO: Demographic and administrative information, along with individual records for each event report; 2) DRUG: Information about drugs/biologics mentioned in the case reports; 3) REAC: Information on adverse drug reactions; 4) OUTC: Patient outcome data; 5) RPSR: Source of the report for each event; 6) THER: Start and end dates of the drug therapy associated with the reported event; 7) INDI: Indications for the drug administration.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData Acquisition and Preprocessing\u003c/h3\u003e\n\u003cp\u003eIn this study, all data downloaded from the FDA website were imported into MySQL 8.0 for preprocessing. A total of 15,362,342 reports were initially obtained from the FAERS database, which were then processed to eliminate duplicates in order to enhance the reliability of the results. As outlined in the README file accompanying each quarterly data package, duplicates were identified and removed based on the \"CASEID,\" in line with FDA_AERS guidelines. The most recent FDA_DT within the same CASEID series was prioritized, and when both CASEID and FDA_DT were identical, the PRIMARYID was used as the filtering criterion. After de-duplication, the number of reports was reduced to 13,045,652 (Fig.\u0026nbsp;1). Additionally, drug names were standardized using Medex_UIMA_1.3.8, while adverse events (AEs) in the FAERS database were categorized and described using the preferred terms (PT) and system organ class (SOC) terms from the latest version of the MedDRA (26.1). Since the FAERS database includes reports for all FDA-approved drugs, we utilized IBM Micromedex as a reference dictionary, retrieving relevant reports for the drug \"Vedolizumab\" using its generic name and brand name \"Entyvio.\"\u003c/p\u003e\n\u003ch3\u003eData Mining and Analysis\u003c/h3\u003e\n\u003cp\u003eIn pharmacovigilance research, disproportionality analysis is a key method for identifying and detecting drug-related adverse reaction signals. This approach involves comparing the frequency ratios observed in the exposed and non-exposed populations using a 2x2 contingency table to assess the strength of association between a drug and an adverse event. In this study, commonly used disproportionality metrics such as the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and the Empirical Bayes Geometric Mean (EBGM) were employed concurrently to detect ADE signals. This strategy allows for cross-validation, reduction of bias, and identification of rare adverse events. All calculations were based on the 2x2 contingency table method, with detailed equations and criteria provided in the supplementary Table (S1). An ADE signal was considered detected when the incidence rate for the selected drug's adverse event was significantly higher than the background frequency and met the criteria of all four algorithms. The higher the value, the stronger the signal, indicating a stronger association between the drug and the adverse event. Serious adverse reactions were defined as those leading to hospitalization, disability, death, or life-threatening conditions. Data processing and statistical analyses were performed using MySQL 8.0, Microsoft Excel 2021, and GraphPad Prism 10.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eFundamental Characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween the first quarter of 2014 and the first quarter of 2024, a total of 13,045,652 reports were included in the FAERS database after excluding duplicate event reports. These reports encompassed 37,214,775 distinct adverse drug reactions. Notably, we selected reports where Vedolizumab was identified as the primary suspected drug (PS), resulting in 50,852 reports that documented 183,083 individual adverse events. A descriptive analysis of the clinical characteristics associated with Vedolizumab-related events is summarized in Table 1.\u003c/p\u003e\n\u003cp\u003eSince its market approval, the number of adverse event (AE) reports associated with Vedolizumab has steadily increased, reaching a total of 12,143 reports across the four quarters of 2023. Regarding gender distribution, the majority of reports included gender information, with a slight predominance of female patients (51.94%) over male patients (41.58%), though the difference was not statistically significant. In terms of age, patients aged between 18 and 65 years represented the largest cohort, comprising 46.93% (23,861 reports), with a median age of 49 years. Geographically, Canada submitted the highest number of reports, totaling 22,571 (44.39%), followed by the United States at 30.36%. Detailed global distribution is presented in\u0026nbsp;Supplementary Figure 1. In terms of report sources, consumers and healthcare professionals were the primary reporters, contributing 54.21% and 29.87% of the total, respectively, with pharmacists (11.70%) and other healthcare professionals (3.56%) following. Notably, 16 reports originated from legal representatives. Regarding outcomes of adverse events, the majority of AE reports were classified as \"other serious\" (67.40%), which somewhat hindered in-depth analysis of the event outcomes. In reports where outcomes were clearly specified, the most common result was hospitalization (27.65%, 14,862 cases), followed by death (3.44%, 1,848 cases), life-threatening conditions (0.68%, 364 cases), and disability (0.63%, 338 cases). Furthermore, although less frequent, 28 reports indicated outcomes requiring intervention to prevent permanent damage, an important consideration. Concerning indications, ulcerative colitis (22,751 reports, 45.0%) and Crohn's disease (20,306 reports, 40.1%) were the most commonly reported indications, consistent with the approved indications by the U.S. Food and Drug Administration (FDA). Other notable indications, aside from those with unknown causes, included inflammatory bowel disease (1,016 reports, 2.0%) and colitis (412 reports, 0.8%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSignal Detection for Vedolizumab\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThrough disproportionality analysis, we identified 24 system organ classes (SOCs) associated with adverse events related to Vedolizumab. Table 2 presents the signal strength and report counts for Vedolizumab across various SOCs. The analysis revealed that, according to at least one of the four analytical methods used, the following SOCs were significantly identified: gastrointestinal disorders (n=51,657, ROR 4.17, PRR 3.28, IC 1.7, EBGM 3.24), pregnancy, puerperium, and perinatal conditions (n=1,772, ROR 2.38, PRR 2.36, IC 1.23, EBGM 2.35), infections and infestations (n=15,804, ROR 1.59, PRR 1.54, IC 0.62, EBGM 1.54), and injury, poisoning and procedural complications (n=25,254, ROR 1.29, PRR 1.25, IC 0.32, EBGM 1.25). These findings highlight the specific organ systems most commonly reported as adversely affected by Vedolizumab. However, they appear inconsistent with the information provided in the drug’s prescribing information and previously published clinical studies. Specifically, while the prescribing information similarly acknowledges gastrointestinal disorders and infections and infestations as common affected systems, it also lists general disorders and administration site conditions, but fails to mention pregnancy, puerperium, and perinatal conditions. Additionally, other common organ systems listed in the prescribing information, such as nervous system disorders, vascular diseases, respiratory, thoracic, and mediastinal diseases, musculoskeletal and connective tissue diseases, and skin and subcutaneous tissue disorders, did not meet the criteria for significance in any of the analytical methods employed.\u003c/p\u003e\n\u003cp\u003eAfter meeting the criteria of all four analytical algorithms, we further identified 103 Vedolizumab-induced adverse event (AE) signals across the 24 system organ classes (SOCs). Table 3 presents the preferred terms (PTs) with at least 100 reports, with all PTs listed in Supplementary Table S2. To mitigate bias due to indications, we excluded PTs related to Vedolizumab’s approved indications (ulcerative colitis, Crohn’s disease, hematochezia, increased bowel frequency, and mucous stools). Even after this exclusion, 22 PTs and 8 corresponding SOCs remained. Among the most frequently reported AEs in our study were poor venous access (728 cases),\u0026nbsp;defaecation urgency (698 cases), and fistulas (406 cases). Other notable AEs included faeces soft , anal abscess, gastrointestinal inflammation, intestinal stenosis, anal fistula, faecal calprotectin increased, proctalgia, anal fissure, abscess intestinal , dyschezia, large intestinal stenosis, sclerosing cholangitis, rectal absces, ileal stenosis, and proctitis. These reports were predominantly centered around gastrointestinal disorders, with only anal abscess and defecation difficulties explicitly recorded in the Vedolizumab prescribing information. Importantly, our data mining revealed several significant AEs not explicitly mentioned in the drug’s prescribing information, including gastrointestinal precancerous lesions (11 cases), abnormal umbilical cord attachment (4 cases), cholangitis sclerosing (115 cases), neurogenic shock (31 cases), colorectal adenoma (13 cases), neoplasm of appendix (6 cases), endocrine neoplasm (3 cases), intestinal adenocarcinoma (7 cases), and abdominal hernia obstructive (5 cases).\u003c/p\u003e\n\u003cp\u003eAs the reports collected in the FAERS database are submitted by a wide range of healthcare professionals, the analysis also revealed several signals unrelated to the drug. These signals were primarily concentrated in the categories of general disorders and administration site conditions, as well as pregnancy, puerperium, and perinatal conditions. The preferred terms (PTs) associated with these signals included therapeutic reaction time decreased, pregnancy, loss of therapeutic response, and drug level decreased, among others. Further details can be found in Table 3.\u003c/p\u003e\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eGastrointestinal System-Related Adverse Drug Events (ADEs)\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eIn our study, after excluding PTs related to the approved indications, the five most commonly reported ADEs within gastrointestinal disorders were defaecation urgency, soft stools, gastrointestinal inflammation, intestinal stenosis, and anal fistula. Notably, among these ADEs, only anal fissures and defecation difficulties were consistent with the drug's prescribing information. In contrast, other adverse events such as urgent defecation urges and anal fistula were not explicitly mentioned in the Vedolizumab prescribing information. It is currently unclear whether these symptoms represent manifestations of the underlying disease or are possibly drug-induced. On one hand, urgent defecation urges and soft stools are common in the disease course of UC and CD. Furthermore, studies have reported that the development of intestinal stenosis is a frequent complication of CD\u003csup\u003e[8, 9]\u003c/sup\u003e, affecting the entire gastrointestinal tract, with approximately 10% of CD patients experiencing colonic stenosis—2 to 3 times more common than ileal stenosis\u003csup\u003e[8, 9]\u003c/sup\u003e. It is less common, but colonic stenosis may also be observed in UC patients. On the other hand, considering the gut-selective mechanism of action of Vedolizumab, the increased risk of certain gastrointestinal disorders appears plausible.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003ePregnancy and Perinatal-Related ADEs\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eOf particular interest is the identification of pregnancy and perinatal-related ADEs within the algorithm-derived SOC, with specific PTs including pregnancy and abnormal umbilical cord attachment. However, the lack of information regarding pregnancy outcomes limits further investigation into the risks of Vedolizumab use during pregnancy and the perinatal period for both the mother and fetus. Evidence from clinical trials suggests that among four studies using Vedolizumab, the incidence of early pregnancy loss was 18% (ranging from 12% to 24%)\u003csup\u003e[10-13]\u003c/sup\u003e, and the incidence of preterm birth was 19% (ranging from 12% to 26%)\u003csup\u003e[10-13]\u003c/sup\u003e. Compared to TNF inhibitors, Vedolizumab-exposed patients showed significantly higher rates of preterm birth, which supports and complements our findings, reinforcing the reliability of our results. Interestingly, four cases of abnormal umbilical cord attachment were reported. As a novel and potentially significant PT, we cannot definitively determine whether these cases were drug- or disease-related. Although no direct evidence currently links Vedolizumab to abnormal umbilical cord attachment, the drug’s mechanism of action—binding to α4β7 integrin to block lymphocyte migration—suggests that abnormal immune responses induced by either the drug or the disease could potentially affect fetal growth and the normal function of the umbilical cord. Clinicians should remain vigilant regarding the potential for pregnancy-related adverse events associated with Vedolizumab.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eInfection and Infestation-Related ADEs\u0026nbsp;\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\u003cp\u003eInfection and infestation-related ADEs primarily involved abscesses, with additional PTs of intestinal abscess and stoma site abscess identified, which were not mentioned in the prescribing information, while anal abscesses were consistent with the listed PTs. Key findings from the Vedolizumab GEMIMI trials indicated that severe infections were more common in Crohn’s disease (CD) patients than in those with ulcerative colitis (UC)\u003csup\u003e[14-16]\u003c/sup\u003e. Abscesses are the most frequently observed severe adverse event in CD patients, typically occurring in the anus, rectum, or perirectal region\u003csup\u003e[14-16]\u003c/sup\u003e, which aligns with our study's results. It is important to note that patients receiving placebo had a higher incidence of abscesses than those treated with Vedolizumab, suggesting that abscesses may be a complication of inflammatory bowel disease (IBD) rather than being specifically related to Vedolizumab. However, some subsequent studies also found contradictory results, with a higher rate of abscesses observed in the Vedolizumab group compared to the control group\u003csup\u003e[14-16]\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\u003cp\u003eMoreover, other intestinal infections induced by Vedolizumab were rare in our findings, with only a small number of cases reporting gastrointestinal bacterial infections, Escherichia coli gastroenteritis, amoebic infections, and other perianal infections (Supplementary Table S2). The drug’s immunosuppressive action in the gut, mediated by binding to α4β7 integrin expressed on gut-homing lymphocytes, is a likely mechanism contributing to the increased risk of intestinal infections and infestations. Clinical trials have also indicated that Clostridium difficile and cytomegalovirus infections were exclusively observed in the Vedolizumab group\u003csup\u003e[14-16]\u003c/sup\u003e, thus highlighting the need for further cohort studies to evaluate the risks of gut and other infections. Stoma site abscesses typically occur as postoperative complications, and a cohort study focused solely on UC patients, which included 88 Vedolizumab-treated patients and 62 patients receiving anti-TNFα therapy within 12 weeks post-surgery, found that more Vedolizumab-treated patients developed superficial surgical site infections (p = 0.047) and ileostomy site skin-mucosa separation (p = 0.047)\u003csup\u003e[17]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eHepatobiliary System-Related ADEs\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eInterestingly, the results of this study reveal that sclerosing cholangitis is the most common ADE associated with the hepatobiliary system, yet it is not explicitly mentioned in the drug’s prescribing information. Multiple studies have indicated that Vedolizumab’s specific targeting of the gut-homing pathway (i.e., the interaction between α4β7 and its ligand MAdCAM-1) is implicated in the pathophysiology of sclerosing cholangitis\u003csup\u003e[18]\u003c/sup\u003e. Activated T cells homing from the gut to the liver may contribute to cholangitis associated with sclerosing cholangitis by upregulating the adhesion molecule MAdCAM-1 and the chemokine CCL, which could facilitate the recruitment of α4β7 integrin-positive T cells into the biliary endothelial cells\u003csup\u003e[19, 20]\u003c/sup\u003e. Therefore, Vedolizumab may play a role in reducing lymphocytic infiltration into the liver in patients with sclerosing cholangitis, thereby mitigating liver and biliary tract inflammation.\u003c/p\u003e\u003cp\u003eSurprisingly, a GETAID multicenter cohort study that included 75 patients with sclerosing cholangitis and active IBD observed that, among 54 patients, 4 [7%] and 4 [11%] exhibited a reduction of at least 50% in serum alkaline phosphatase (ALP) levels from baseline to week 30 and week 54, respectively. However, no significant changes were observed in serum liver enzyme levels at either week 30 or week 54 compared to baseline. Overall, liver function tests did not show improvement, suggesting that Vedolizumab is ineffective in treating sclerosing cholangitis\u003csup\u003e[21]\u003c/sup\u003e. Epidemiological studies on sclerosing cholangitis and IBD demonstrate that they often co-occur, with similar geographic prevalence patterns, and that IBD is present in the majority of sclerosing cholangitis patients\u003csup\u003e[22]\u003c/sup\u003e. Therefore, it is difficult to determine whether sclerosing cholangitis is a symptom of the underlying disease or an adverse drug reaction induced by Vedolizumab.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn summary, this study provides evidence for the safety evaluation of Vedolizumab through multidimensional and multilevel analysis. Notably, although some adverse events (AEs), such as abnormal umbilical cord attachment, occur at a relatively low frequency, their high signal strength warrants further attention and investigation. Moreover, the study identified several notable adverse reactions not mentioned in the drug\u0026rsquo;s prescribing information, such as anal fistula, intestinal abscess, and sclerosing cholangitis. This underscores the importance for healthcare professionals to closely monitor the occurrence of adverse events in clinical practice to enable timely intervention. To obtain a more comprehensive and precise understanding, future research should adopt more rigorous prospective study designs, combining clinical trials with epidemiological studies, with the goal of more accurately assessing the safety risks associated with Vedolizumab.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eFAERS: the FDA Adverse Event Reporting System\u003c/p\u003e\n\u003cp\u003eADEs: Adverse drug events\u003c/p\u003e\n\u003cp\u003eROR: Reporting Odds Ratio\u003c/p\u003e\n\u003cp\u003ePRR: Proportional Reporting Ratio\u003c/p\u003e\n\u003cp\u003eBCPNN: Bayesian Confidence Propagation Neural Network\u003c/p\u003e\n\u003cp\u003eEBGM: Empirical Bayesian Geometric Mean\u003c/p\u003e\n\u003cp\u003eSOC: system organ class\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material; further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funds were received to support this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no relevant financial or non-financial interests to be disclosed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaterial preparation, data collection and analysis were performed by Guanghui Yuan and Jie Liu. Yi Xu and Zhaowei Shan was responsible for research design.The first draft of the manuscript was written by Guanghui Yuan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. All authors contributed to this article and approved the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eORDAS I, ECKMANN L, TALAMINI M, et al. Ulcerative colitis[J]. Lancet, 2012,380(9853): 1606-1619.\u003c/li\u003e\n\u003cli\u003eLe BERRE C, HONAP S, PEYRIN-BIROULET L. Ulcerative colitis[J]. Lancet, 2023,402(10401): 571-584.\u003c/li\u003e\n\u003cli\u003eMCCOUBREY L E, SEEGOBIN N, SANGFUANG N, et al. The colon targeting efficacies of mesalazine medications and their impacts on the gut microbiome[J]. J Control Release, 2024,369: 630-641.\u003c/li\u003e\n\u003cli\u003eTORRES J, MEHANDRU S, COLOMBEL J F, et al. Crohn\u0026apos;s disease[J]. Lancet, 2017,389(10080): 1741-1755.\u003c/li\u003e\n\u003cli\u003ePOOLE R M. Vedolizumab: first global approval[J]. Drugs, 2014,74(11): 1293-1303.\u003c/li\u003e\n\u003cli\u003eATTAUABI M, MADSEN G R, BENDTSEN F, et al. Vedolizumab as the first line of biologic therapy for ulcerative colitis and Crohn\u0026apos;s disease - a systematic review with meta-analysis[J]. Dig Liver Dis, 2022,54(9): 1168-1178.\u003c/li\u003e\n\u003cli\u003eENGEL T, UNGAR B, YUNG D E, et al. Vedolizumab in IBD-Lessons From Real-world Experience; A Systematic Review and Pooled Analysis[J]. J Crohns Colitis, 2018,12(2): 245-257.\u003c/li\u003e\n\u003cli\u003eLOUIS E, COLLARD A, OGER A F, et al. Behaviour of Crohn\u0026apos;s disease according to the Vienna classification: changing pattern over the course of the disease[J]. Gut, 2001,49(6): 777-782.\u003c/li\u003e\n\u003cli\u003eCOSNES J, CATTAN S, BLAIN A, et al. Long-term evolution of disease behavior of Crohn\u0026apos;s disease[J]. Inflamm Bowel Dis, 2002,8(4): 244-250.\u003c/li\u003e\n\u003cli\u003eBAR-GIL S A, BEN Y A, LIVOVSKY D M, et al. Exposure to Vedolizumab in IBD Pregnant Women Appears of Low Risk for Mother and Neonate: A First Prospective Comparison Study[J]. Am J Gastroenterol, 2019,114(7): 1172-1175.\u003c/li\u003e\n\u003cli\u003eMAHADEVAN U, VERMEIRE S, LASCH K, et al. Vedolizumab exposure in pregnancy: outcomes from clinical studies in inflammatory bowel disease[J]. Aliment Pharmacol Ther, 2017,45(7): 941-950.\u003c/li\u003e\n\u003cli\u003eMOENS A, van HOEVE K, HUMBLET E, et al. Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab[J]. J Crohns Colitis, 2019,13(1): 12-18.\u003c/li\u003e\n\u003cli\u003eMOENS A, van der WOUDE C J, JULSGAARD M, et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study[J]. Aliment Pharmacol Ther, 2020,51(1): 129-138.\u003c/li\u003e\n\u003cli\u003eFEAGAN B G, RUTGEERTS P, SANDS B E, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis[J]. N Engl J Med, 2013,369(8): 699-710.\u003c/li\u003e\n\u003cli\u003eSANDBORN W J, FEAGAN B G, RUTGEERTS P, et al. Vedolizumab as induction and maintenance therapy for Crohn\u0026apos;s disease[J]. N Engl J Med, 2013,369(8): 711-721.\u003c/li\u003e\n\u003cli\u003eCOLOMBEL J F, SANDS B E, RUTGEERTS P, et al. The safety of vedolizumab for ulcerative colitis and Crohn\u0026apos;s disease[J]. Gut, 2017,66(5): 839-851.\u003c/li\u003e\n\u003cli\u003eLIGHTNER A L, RAFFALS L E, MATHIS K L, et al. Postoperative Outcomes in Vedolizumab-Treated Patients Undergoing Abdominal Operations for Inflammatory Bowel Disease[J]. J Crohns Colitis, 2017,11(2): 185-190.\u003c/li\u003e\n\u003cli\u003eEKSTEEN B, GRANT A J, MILES A, et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis[J]. J Exp Med, 2004,200(11): 1511-1517.\u003c/li\u003e\n\u003cli\u003eBURAK K, ANGULO P, PASHA T M, et al. Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis[J]. Am J Gastroenterol, 2004,99(3): 523-526.\u003c/li\u003e\n\u003cli\u003eEKSTEEN B, MORA J R, HAUGHTON E L, et al. Gut homing receptors on CD8 T cells are retinoic acid dependent and not maintained by liver dendritic or stellate cells[J]. Gastroenterology, 2009,137(1): 320-329.\u003c/li\u003e\n\u003cli\u003eCARON B, PEYRIN-BIROULET L, PARIENTE B, et al. Vedolizumab Therapy is Ineffective for Primary Sclerosing Cholangitis in Patients With Inflammatory Bowel Disease: A GETAID Multicentre Cohort Study[J]. J Crohns Colitis, 2019,13(10): 1239-1247.\u003c/li\u003e\n\u003cli\u003evan MUNSTER K N, BERGQUIST A, PONSIOEN C Y. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two?[J]. J Hepatol, 2024,80(1): 155-168.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"561\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 155px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase number\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase proportion, %\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eYear\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e4.31\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e4.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3381\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e6.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e4001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e7.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e4574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e8.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e7444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e14.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e7817\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e15.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e12143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e23.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e5424\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e10.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e26410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e51.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e21144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e41.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eAge_yr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eAge_yrQ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026lt;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e918\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 18~45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e13032\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e25.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 45~65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e10829\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e21.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 65~75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e4843\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e9.52\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026gt;=75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2939\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e5.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; unknow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e18291\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e35.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003ewt\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e69.60(58.00,84.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eReporter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Consumer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e27568\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e54.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Physician\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e15191\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e29.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Pharmacist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e5950\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e11.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Other health-professional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1809\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e3.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; unknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Lawyer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eReported countries\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Canada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e22571\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e44.39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; United States\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e15440\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e30.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; United Kingdom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e4.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Australia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e2042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e4.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Germany\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1053\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; Japan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1035\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eRoute\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; intravenous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e41775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e82.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e6822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e13.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; subcutaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1389\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e2.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; intravenous drip\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e722\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; transmammary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e \u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; other serious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e3622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e67.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; hospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e14862\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e27.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e1848\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; life threatening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; disability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e338\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; congenital anomaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; required intervention to Prevent Permanent Impairment/Damage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 155px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 136px;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 2\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSOC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase Reports\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eROR(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRR(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003echisq\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC(IC025)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEBGM(EBGM05)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e51657\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e4.17(4.13, 4.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3.28(3.28, 3.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e88030.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1.7(1.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3.24(3.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003epregnancy, puerperium and perinatal conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1772\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2.38(2.27, 2.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2.36(2.27, 2.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1384.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e1.23(1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e2.35(2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e15804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.59(1.57, 1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.54(1.51, 1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e3156.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.62(0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1.54(1.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e25254\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1.29(1.27, 1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1.25(1.23, 1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1417.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e0.32(0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e1.25(1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e9460\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.84(0.82, 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.85(0.83, 0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e272.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.24(-0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.85(0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e8425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.83(0.82, 0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.84(0.82, 0.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e265.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.25(-0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.84(0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003egeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e29074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.82(0.81, 0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.85(0.83, 0.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e929.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.23(-0.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.85(0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003ehepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.78(0.74, 0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.79(0.74, 0.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e71.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.35(-0.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.79(0.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.75(0.73, 0.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.76(0.73, 0.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e228.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.4(-0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.76(0.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eear and labyrinth disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.7(0.64, 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.7(0.65, 0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e75.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.51(-0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.7(0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.63(0.61, 0.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.64(0.62, 0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e529.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.65(-0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.64(0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e5728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.63(0.62, 0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.64(0.63, 0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1188.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.63(-0.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.64(0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e8406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.53(0.52, 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.55(0.54, 0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e3373.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.86(-0.89)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.55(0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eeye disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1971\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.52(0.5, 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.52(0.5, 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e863.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.93(-0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.53(0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e734\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.5(0.46, 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.5(0.46, 0.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e367.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.99(-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.5(0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e2874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.5(0.48, 0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.5(0.48, 0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1448.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-0.99(-1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.5(0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eendocrine disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.49(0.43, 0.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.49(0.44, 0.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e127.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.02(-1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.49(0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e5116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.46(0.45, 0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.48(0.47, 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e3081.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.06(-1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.48(0.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003erenal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1737\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.46(0.44, 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.47(0.45, 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1068.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.09(-1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.47(0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003ecardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.42(0.4, 0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.43(0.41, 0.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1446.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.23(-1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.43(0.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e858\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.37(0.35, 0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.38(0.36, 0.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e888.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.4(-1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.38(0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e1109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.35(0.33, 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.35(0.33, 0.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e1326.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.49(-1.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.36(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003epsychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e3666\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.34(0.33, 0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.35(0.34, 0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e4611.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.5(-1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.35(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33px;\"\u003e\n \u003cp\u003econgenital, familial and genetic disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.33(0.29, 0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.33(0.29, 0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 8px;\"\u003e\n \u003cp\u003e241.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 9px;\"\u003e\n \u003cp\u003e-1.58(-1.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.34(0.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 3\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSOC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCase Reports\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eROR(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePRR(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003echisq\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIC(IC025)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEBGM(EBGM05)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003ecolitis ulcerative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e8819\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e99.81(97.27, 102.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e95.05(93.21, 96.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e558741.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e6.02(5.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e64.98(63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003ecrohn\u0026apos;s disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e6678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e40.71(39.64, 41.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e39.26(38.5, 40.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e208754.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5.05(5.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e33.04(32.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003ehaematochezia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e3169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19.92(19.2, 20.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19.59(18.84, 20.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e51023.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.17(4.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e17.95(17.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003efrequent bowel movements\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e2445\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e33.24(31.84, 34.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e32.81(31.55, 34.12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e64903.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.83(4.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e28.37(27.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003etherapeutic reaction time decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e1758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1734.45(1501.69, 2003.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1717.81(1497.58, 1970.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e317773.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e7.51(7.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e181.85(161.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003epregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e1189\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e31.25(29.39, 33.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e31.05(29.28, 32.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e29985.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.76(4.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e27.05(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003emucous stools\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e59.9(55.17, 65.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e59.66(55.16, 64.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e32873.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5.53(5.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e46.3(43.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003epoor venous access\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e728\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e26.31(24.35, 28.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e26.21(24.23, 28.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e15630.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.54(4.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e23.32(21.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003edrug level decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e707\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.2(21.46, 25.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.11(21.37, 24.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e13426.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.38(4.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.85(19.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003edefaecation urgency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e698\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e39.72(36.62, 43.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e39.57(36.59, 42.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e21949.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e5.06(4.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e33.26(31.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003eloss of therapeutic response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e613\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e132.63(119.78, 146.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e132.19(119.85, 145.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e48267.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e6.33(6.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e80.34(73.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003efistula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e406\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.04(11.79, 14.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.01(11.8, 14.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4230.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.62(3.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e12.29(11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003efaeces soft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e366\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e15.18(13.65, 16.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e15.15(13.74, 16.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4500.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.82(3.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e14.16(12.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003eanal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e352\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e21.85(19.58, 24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e21.81(19.39, 24.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e6310.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.31(4.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e19.79(18.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003egastrointestinal inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e342\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e14(12.54, 15.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.97(12.42, 15.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3853.31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.72(3.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e13.13(11.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eintestinal stenosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e298\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e25.22(22.35, 28.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e25.18(22.39, 28.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e6153.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.49(4.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e22.5(20.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eanal fistula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e18.66(16.54, 21.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e18.63(16.56, 20.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4416.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.1(3.93)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e17.15(15.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003efaecal calprotectin increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e238\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.04(20.15, 26.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.01(20.06, 26.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4499.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.38(4.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.76(18.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eproctalgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.71(11.09, 14.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.69(11.06, 14.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2250.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.59(3.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e12(10.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eanal fissure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.48(11.72, 15.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e13.47(11.74, 15.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2250.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.67(3.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e12.69(11.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003eabscess intestinal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e22.51(18.79, 26.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e22.49(18.85, 26.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2421.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.35(4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.34(17.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003edyschezia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.82(10.75, 15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.81(10.74, 15.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1341.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.6(3.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e12.11(10.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003elarge intestinal stenosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e20.78(17.31, 24.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e20.77(17.41, 24.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2167.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.24(3.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e18.93(16.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003echolangitis sclerosing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19.16(15.82, 23.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19.14(15.73, 23.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1806.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.14(3.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e17.58(14.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\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: 17px;\"\u003e\n \u003cp\u003erectal abscess\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e109\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e22.7(18.62, 27.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e22.68(18.64, 27.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e2031.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.36(4.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.5(17.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eileal stenosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.29(18.99, 28.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23.28(19.14, 28.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e1969.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e4.39(4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e20.98(17.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17px;\"\u003e\n \u003cp\u003eproctitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7px;\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.54(10.24, 15.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12.53(10.3, 15.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e999.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 6px;\"\u003e\n \u003cp\u003e3.57(3.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 11px;\"\u003e\n \u003cp\u003e11.86(10.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Vedolizumab, pharmacovigilance, adverse event, FAERS","lastPublishedDoi":"10.21203/rs.3.rs-6552177/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6552177/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study aims to assess the adverse event profile of Vedolizumab using FDA Adverse Event Reporting System (FAERS) data to identify potential safety risks and support clinical use.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eFAERS data from Q1 2014 to Q1 2024 were analyzed. Adverse drug events (ADEs) related to Vedolizumab were extracted and evaluated using four signal detection methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Analysis included 50,852 reports identifying vedolizumab as the primary suspected drug. At the system organ class (SOC) level, it was significantly associated with gastrointestinal disorders, pregnancy-related conditions, infections, and procedural complications. Using all four algorithms, 103 adverse event (AE) signals were detected, with venous access complications, urgency of defecation, and fistulas being most common. Notable AEs absent from the drug label were also identified.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This study underscores certain safety risks of Vedolizumab, particularly gastrointestinal reactions and infections, providing valuable evidence for clinical decision-making and future research.\u003c/p\u003e","manuscriptTitle":"Vedolizumab adverse event profile: pharmacovigilance study based on FDA Adverse Event Reporting System (FAERS)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-11 12:26:35","doi":"10.21203/rs.3.rs-6552177/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-08T08:46:17+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"294169214190349783742254927892844977312","date":"2025-07-22T09:20:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-16T17:03:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-10T22:15:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-10T14:32:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"99031011549117219038521666005325974012","date":"2025-07-09T13:43:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"211729929254853869883766109319343591633","date":"2025-07-09T13:35:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"172804696634343320775110558609201366309","date":"2025-07-09T10:44:44+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-09T10:19:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-22T16:07:57+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-05-22T16:06:39+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-04T15:46:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-04T15:45:02+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2a3e0f23-eef5-4ab5-8e9c-545de109d3a2","owner":[],"postedDate":"July 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":51361948,"name":"Biological sciences/Computational biology and bioinformatics"},{"id":51361949,"name":"Health sciences/Gastroenterology"}],"tags":[],"updatedAt":"2025-11-03T15:59:08+00:00","versionOfRecord":{"articleIdentity":"rs-6552177","link":"https://doi.org/10.1038/s41598-025-21609-y","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-10-28 15:56:52","publishedOnDateReadable":"October 28th, 2025"},"versionCreatedAt":"2025-07-11 12:26:35","video":"","vorDoi":"10.1038/s41598-025-21609-y","vorDoiUrl":"https://doi.org/10.1038/s41598-025-21609-y","workflowStages":[]},"version":"v1","identity":"rs-6552177","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6552177","identity":"rs-6552177","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}