Risk factors and subgroups analysis of Enasidenib in treating Acute Myelogenous Leukemia : a pharmacovigilance study based on FAERS database

Risk factors and subgroups analysis of Enasidenib in treating Acute Myelogenous Leukemia : a pharmacovigilance study based on FAERS database | 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 Risk factors and subgroups analysis of Enasidenib in treating Acute Myelogenous Leukemia : a pharmacovigilance study based on FAERS database Jiangchuan Xie, Qian Gao, Yu Qin, Linli XIE, Yongchuan Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6698707/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Enasidenib, an isocitrate dehydrogenase inhibitor (IDHI) that selectively inhibits IDHI-2, is currently approved for treating Acute Myelogenous Leukemia(AML). This study identified and characterized adverse events (AEs) significantly related to IDHI in treating AML and compared the differences of subgroups to provide clinical reference. AEs reports were collected from the United States Food and Drug Administration Adverse Event Reporting System(FAERS). Enasidenib’s AEs were collected from Q3 2017 to Q3 2024. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network(BCPNN) were used. When the lower limit of the 95% confidence interval (CI) of ROR > 1.0 and (IC-2SD)>0 was considered the threshold for a signal. A total of 2098 AE reports were retrieved from FAERS. Reports for males were higher than females, and patients aged 65–85 years reported the highest number of AEs. Interestingly, 52 PTs were classified as unexpected AEs, such as fatigue, asthenia, platelet count decreased, etc. There are similarities and differences in the presentation of enasidenib-related AEs in subgroups of different genders and ages. Gender-specific and age-specific patients should be concerned about the occurrence of appropriate AEs when taking enasidenib. Our study provided evidence for enasidenib in the treatment of AML. Biological sciences/Cancer Biological sciences/Drug discovery Biological sciences/Immunology Health sciences/Oncology FAERS enasidenib isocitrate dehydrogenase inhibitor adverse events acute myelogenous leukemia Figures Figure 1 Figure 2 Introduction Leukemias are a category of life-threatening haematological malignancies, with significant morbidity and mortality [ 1 – 5 ]. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, the number of patients diagnosed with AML in the United States, China, and India in 2021 was 21533,17835 and 11040, respectively[ 2 ]. What’s more, AML occurs more often in older adults, especially at age 65 and over [ 6 – 8 ]. The routine treatment process for AML includes: chemotherapy, conventional, and allogeneic hematopoietic stem cell transplant(allo-HSCT) [ 9 – 11 ]. However, chemotherapy has significant side effects [ 12 , 13 ], and conventional targeted therapy is prone to drug resistance [ 14 , 15 ]. Furthermore, allo-HSCT is not a once-for-all approach as almost 50% of patients relapse and the risk of non-relapse mortality is high [ 11 ]. Thus, new exploration has never stopped. In recent years, more than 95% of detectable somatic mutations in patients with AML have been found [ 16 ]. Of them, mutations on isocitrate dehydrogenase have been detected in multiple tumors [ 17 – 23 ], while AML, accounts for 20%. These findings open up new tracks for the treatment of AML. Enasidenib is an orally small molecule of IDHI-2, originally approved for the treatment of adult patients with IDH2-mutated AML in 2017 by the Food and Drug Administration (FDA). It is reported that enasidenib significantly improved the rate of complete response/complete response with incomplete count recovery (CR/CRi) and prolonged the median overall survival in patients with R/R AML [ 24 ]. Numerous studies showed good tolerance of enasidenib in patients with IDH2-mutated AML [ 3 , 5 , 25 , 26 ]. Along with its extensive usage, the number of reported AEs also increased. So, it is essential to pay close attention to its latent AEs. Previously reported AEs were mainly derived from clinical trials, which may differ from the real-world population. Therefore, it is quite necessary to research the safety of enasidenib based on the postmarketing world data. The FDA Adverse Event Reporting System (FAERS) is a public free spontaneous pharmacovigilance database [ 27 , 28 ], that contains a large number of real-world safety signals data which may have been ignored in clinical studies. This study aims to identify and characterize AEs significantly related to enasidenib in treating AML and to provide valuable clinical references. Methods Data source Our study collected enasidenib’ AEs data from the FAERS Quarterly Data Extract Files between the third quarter of 2017 (FDA marketing approval of enasidenib for the treatment of AML) and the third quarter of 2024. Drug identification Reports involving enasidenib for AML. During the data mining process, they were identified in the FAERS by brand and generic name. Regression analysis As shown in Table S1 , we assessed the relationship between AEs and enasidenib using the Proportional Reporting Ratio (PRR) and Bayesian confidence propagation neural network(BCPNN) using the contingency table calculator from Open Vigil. A risk signal was considered when the lower limit of the corresponding 95% CI was > 1, a > 3, and IC-2SD>0. Table S2 shows the calculation formula. Data were analyzed using MYSQL (version 8.0) and R studio software (version 9.1.0). Results Baseline characteristics of enasidenib As shown in Table 1, for the treatment of AML, a total of 2098 AE reports were retrieved. In terms of gender, reports for males were higher than females(40.5% for female, 53.0% for male). As for age composition, the highest proportion is 65-85 years old (39.3%). In 2020, the number of reported AEs is the highest (23.1%). What's more, hospitalization was the most common outcome for enasidenib (26.5% ), and the proportion of deaths is relatively high(25.5%). The United States, and France reported the highest number of AEs. Table 1. Characteristics of reports-all reports for enasidenib (Q3 2017 to Q3 2024). Items Case number=2098 Gender Female 849 40.5% Male 1111 53.0% Uknown 138 6.6% Weight ＜50 kg 25 1.2% 50～100 kg 373 17.8% ＞100 kg 25 1.2% Missing 1675 79.8% Age ＜18 8 0.4% 18～64.9 324 15.4% 65～85 825 39.3% >85 55 2.6% Missing 886 42.2% Reporter Customer 364 17.3% Health Professional 527 25.1% Medical Doctor 598 28.5% Others 395 18.8% Pharmacists 205 9.8% Unknown 9 0.4% Reporting country The United States 1604 76.5% France 129 6.2% Others 365 17.3% Years 2017 81 3.9% 2018 318 15.2% 2019 376 17.9% 2020 485 23.1% 2021 338 16.1% 2022 206 9.8% 2023 115 5.5% 2024 179 8.5% Outcomes Hospitalization 555 26.5% Death 536 25.5% Life-threatening 48 2.3% Disability 11 0.5% Other serious outcomes 233 11.1% Missing 715 34.1% Disproportionality analysis As shown in Table 2, the disproportionality at the system organ class (SOC) level of enasidenib was observed. AEs presented eight areas of toxicity: gastrointestinal disorders, general disorders and administration site conditions, investigations, metabolism and nutrition disorders, musculoskeletal and connective tissue disorders, neoplasms benign, malignant and unspecified, nervous system disorders, and psychiatric disorders. Table 2. Signal strength of reports of enasidenib at the system organ class (SOC) level in the FAERS database. SOC Case number ROR(95%Cl) IC(IC025) blood and lymphatic system disorders 185 0.36 ( 0.31 - 0.42 ) -1.32 ( -1.53 ) cardiac disorders 47 0.41 ( 0.31 - 0.55 ) -1.24 ( -1.66 ) congenital, familial and genetic disorders 1 0.15 ( 0.02 - 1.09 ) -2.67 ( -4.72 ) ear and labyrinth disorders 4 0.83 ( 0.31 - 2.24 ) -0.26 ( -1.58 ) endocrine disorders 3 0.55 ( 0.18 - 1.72 ) -0.84 ( -2.3 ) eye disorders 17 0.79 ( 0.49 - 1.28 ) -0.33 ( -1.02 ) *gastrointestinal disorders 425 1.65 ( 1.48 - 1.83 ) 0.63 ( 0.48 ) *general disorders and administration site conditions 861 1.48 ( 1.37 - 1.6 ) 0.44 ( 0.33 ) hepatobiliary disorders 37 0.55 ( 0.39 - 0.76 ) -0.84 ( -1.31 ) infections and infestations 368 0.63 ( 0.56 - 0.7 ) -0.58 ( -0.73 ) injury, poisoning and procedural complications 172 0.53 ( 0.45 - 0.61 ) -0.85 ( -1.07 ) immune system disorders 23 0.45 ( 0.3 - 0.69 ) -1.1 ( -1.7 ) *investigations 522 1.33 ( 1.21 - 1.46 ) 0.35 ( 0.22 ) *metabolism and nutrition disorders 136 1.55 ( 1.3 - 1.85 ) 0.59 ( 0.33 ) *musculoskeletal and connective tissue disorders 122 2.19 ( 1.82 - 2.64 ) 1.05 ( 0.78 ) *neoplasms benign, malignant and unspecified (incl cysts and polyps) 271 1.39 ( 1.22 - 1.58 ) 0.43 ( 0.24 ) *nervous system disorders 227 1.69 ( 1.47 - 1.93 ) 0.69 ( 0.49 ) renal and urinary disorders 64 0.93 ( 0.72 - 1.19 ) -0.11 ( -0.47 ) skin and subcutaneous tissue disorders 116 1.13 ( 0.93 - 1.36 ) 0.16 ( -0.12 ) respiratory, thoracic and mediastinal disorders 175 1.11 ( 0.95 - 1.29 ) 0.14 ( -0.09 ) vascular disorders 54 0.86 ( 0.66 - 1.13 ) -0.2 ( -0.6 ) *psychiatric disorders 70 2.01 ( 1.57 - 2.57 ) 0.95 ( 0.59 ) social circumstances 2 0.38 ( 0.09 - 1.53 ) -1.37 ( -3.05 ) surgical and medical procedures 48 0.42 ( 0.32 - 0.56 ) -1.2 ( -1.62 ) reproductive system and breast disorders 2 0.37 ( 0.09 - 1.49 ) -1.41 ( -3.09 ) *indicates statistically significant signals in the algorithm. Abbreviations: ROR, reporting odds ratio; CI, confidence interval. There are 78 positive signal different preferred terms (PTs) in at least 3 cases. Table 3 lists the number of PTs for each corresponding SOC, and others are described in Table S3. Interestingly, among the 78 PTs, 52 were uncovered in the drug label, such as fatigue, asthenia, platelet count decreased, full blood count decreased, dizziness, constipation, etc. Table 3. Positive signal of the preferred term (PT) and the clinical priority assessing results. SOC PT Case number ROR(95%Cl) IC(IC025) blood and lymphatic system disorders hyperleukocytosis 7 3.75 ( 1.7 - 8.27 ) 1.77 ( 0.68 ) thrombocytosis 4 5.2 ( 1.79 - 15.17 ) 2.18 ( 0.77 ) gastrointestinal disorders nausea 118 2.86 ( 2.36 - 3.47 ) 1.4 ( 1.12 ) diarrhoea 89 2.35 ( 1.89 - 2.92 ) 1.15 ( 0.83 ) *constipation 31 1.82 ( 1.27 - 2.63 ) 0.82 ( 0.29 ) abdominal pain upper 14 2.95 ( 1.7 - 5.12 ) 1.46 ( 0.68 ) abdominal discomfort 14 3.65 ( 2.09 - 6.38 ) 1.74 ( 0.94 ) *dry mouth 5 3.6 ( 1.41 - 9.14 ) 1.72 ( 0.46 ) general disorders and administration site conditions *fatigue 132 3.85 ( 3.2 - 4.63 ) 1.77 ( 1.5 ) *asthenia 56 2.05 ( 1.56 - 2.7 ) 0.97 ( 0.58 ) peripheral swelling 23 4.26 ( 2.74 - 6.62 ) 1.93 ( 1.3 ) *feeling abnormal 8 2.28 ( 1.11 - 4.69 ) 1.12 ( 0.12 ) *influenza like illness 3 4.31 ( 1.28 - 14.58 ) 1.95 ( 0.38 ) hepatobiliary disorders gallbladder disorder 3 4.31 ( 1.28 - 14.58 ) 1.95 ( 0.38 ) immune system disorders *seasonal allergy 3 20.49 ( 4.58 - 91.6 ) 3.6 ( 1.83 ) infections and infestations *nasopharyngitis 7 2.99 ( 1.37 - 6.53 ) 1.48 ( 0.4 ) *coronavirus infection 3 4.31 ( 1.28 - 14.58 ) 1.95 ( 0.38 ) injury, poisoning and procedural complications *fall 24 1.91 ( 1.26 - 2.89 ) 0.88 ( 0.29 ) *transfusion reaction 3 3.56 ( 1.07 - 11.87 ) 1.71 ( 0.16 ) investigations *platelet count decreased 82 1.31 ( 1.05 - 1.64 ) 0.37 ( 0.04 ) *full blood count decreased 55 6.15 ( 4.58 - 8.25 ) 2.37 ( 1.94 ) weight decreased 27 3.45 ( 2.31 - 5.15 ) 1.66 ( 1.08 ) blood bilirubin increased 25 4.31 ( 2.83 - 6.58 ) 1.94 ( 1.34 ) *red blood cell count decreased 23 2.47 ( 1.61 - 3.79 ) 1.23 ( 0.61 ) white blood cell count increased 18 2.59 ( 1.6 - 4.21 ) 1.29 ( 0.6 ) *haemoglobin abnormal 16 3.25 ( 1.93 - 5.45 ) 1.58 ( 0.85 ) weight increased 13 3.32 ( 1.87 - 5.92 ) 1.62 ( 0.8 ) *eastern cooperative oncology group performance status worsened 12 82.16 ( 26.49 - 254.86 ) 4.41 ( 3.34 ) neutrophil count abnormal 11 6.14 ( 3.19 - 11.82 ) 2.38 ( 1.46 ) platelet count abnormal 9 3.08 ( 1.54 - 6.13 ) 1.52 ( 0.55 ) white blood cell count abnormal 8 2.35 ( 1.14 - 4.84 ) 1.16 ( 0.16 ) blood potassium decreased 7 2.48 ( 1.15 - 5.39 ) 1.24 ( 0.17 ) *blood pressure decreased 6 3.42 ( 1.46 - 7.99 ) 1.65 ( 0.49 ) liver function test increased 6 3.22 ( 1.38 - 7.5 ) 1.58 ( 0.42 ) blood uric acid increased 6 4.97 ( 2.08 - 11.87 ) 2.12 ( 0.94 ) *full blood count increased 3 13.66 ( 3.42 - 54.65 ) 3.24 ( 1.53 ) *bone marrow myelogram abnormal 3 10.25 ( 2.72 - 38.64 ) 2.95 ( 1.28 ) metabolism and nutrition disorders decreased appetite 80 5.33 ( 4.18 - 6.78 ) 2.19 ( 1.84 ) *gout 5 3.25 ( 1.29 - 8.23 ) 1.59 ( 0.34 ) musculoskeletal and connective tissue disorders *arthralgia 20 2.74 ( 1.73 - 4.34 ) 1.36 ( 0.7 ) bone pain 16 6.45 ( 3.74 - 11.12 ) 2.43 ( 1.66 ) *pain in extremity 14 2.04 ( 1.18 - 3.51 ) 0.97 ( 0.2 ) *joint swelling 12 9.13 ( 4.74 - 17.55 ) 2.82 ( 1.92 ) *muscular weakness 8 2.23 ( 1.08 - 4.59 ) 1.1 ( 0.09 ) *musculoskeletal pain 5 4.56 ( 1.77 - 11.75 ) 2.02 ( 0.74 ) *arthritis 5 4.41 ( 1.71 - 11.34 ) 1.97 ( 0.7 ) *back disorder 4 13.66 ( 4.11 - 45.4 ) 3.24 ( 1.72 ) *neck pain 3 3.73 ( 1.11 - 12.45 ) 1.76 ( 0.21 ) *musculoskeletal stiffness 3 3.9 ( 1.16 - 13.09 ) 1.82 ( 0.27 ) *myositis 3 3.9 ( 1.16 - 13.09 ) 1.82 ( 0.27 ) neoplasms benign, malignant and unspecified (incl cysts and polyps) differentiation syndrome 76 13.9 ( 10.53 - 18.34 ) 3.24 ( 2.86 ) nervous system disorders *dizziness 31 2.59 ( 1.79 - 3.75 ) 1.29 ( 0.76 ) *headache 21 1.76 ( 1.13 - 2.74 ) 0.78 ( 0.14 ) taste disorder 19 13.71 ( 7.9 - 23.81 ) 3.24 ( 2.49 ) dysgeusia 15 12.84 ( 6.95 - 23.74 ) 3.18 ( 2.34 ) *somnolence 12 3.77 ( 2.06 - 6.91 ) 1.78 ( 0.93 ) *neuropathy peripheral 9 2.86 ( 1.44 - 5.69 ) 1.42 ( 0.46 ) *paraesthesia 7 3.54 ( 1.61 - 7.79 ) 1.7 ( 0.61 ) *hypersomnia 6 7.81 ( 3.15 - 19.36 ) 2.65 ( 1.43 ) *hypoaesthesia 6 4 ( 1.7 - 9.43 ) 1.85 ( 0.69 ) *balance disorder 5 2.73 ( 1.09 - 6.86 ) 1.36 ( 0.12 ) *ageusia 4 6.43 ( 2.16 - 19.12 ) 2.43 ( 1 ) *dementia 3 5.46 ( 1.58 - 18.88 ) 2.24 ( 0.65 ) psychiatric disorders *insomnia 17 5.06 ( 3.01 - 8.5 ) 2.14 ( 1.41 ) *sleep disorder 5 6.83 ( 2.56 - 18.22 ) 2.5 ( 1.19 ) *depressed mood 5 3.8 ( 1.49 - 9.68 ) 1.79 ( 0.53 ) renal and urinary disorders renal disorder 9 2.37 ( 1.2 - 4.68 ) 1.17 ( 0.22 ) *pollakiuria 5 5.69 ( 2.17 - 14.93 ) 2.29 ( 1 ) *nephrolithiasis 4 5.75 ( 1.96 - 16.92 ) 2.3 ( 0.88 ) *chromaturia 4 7.29 ( 2.42 - 21.97 ) 2.58 ( 1.13 ) respiratory, thoracic and mediastinal disorders dyspnoea 51 2.94 ( 2.2 - 3.93 ) 1.45 ( 1.03 ) cough 22 2.74 ( 1.77 - 4.25 ) 1.36 ( 0.73 ) *rhinorrhoea 5 7.19 ( 2.68 - 19.27 ) 2.56 ( 1.25 ) *chronic obstructive pulmonary disease 5 3.42 ( 1.35 - 8.66 ) 1.65 ( 0.4 ) *upper-airway cough syndrome 3 27.32 ( 5.51 - 135.42 ) 3.82 ( 2.01 ) skin and subcutaneous tissue disorders *pruritus 19 2.21 ( 1.39 - 3.54 ) 1.08 ( 0.41 ) *acute febrile neutrophilic dermatosis 7 2.45 ( 1.13 - 5.32 ) 1.22 ( 0.15 ) surgical and medical procedures *hospitalisation 47 1.79 ( 1.33 - 2.41 ) 0.79 ( 0.36 ) *indicates unexpected AEs in the algorithm. Time-to-onset analysis The time from enasidenib use to AEs occurrence was assessed and shown in Figure 1. The median time to the AEs was 46 days (IQR 17-118 days), and 0-30 days, 31-60 days after medication accounted for 38.2% and 16.5%. And Table 4 showed the median time to high-frequency PTs Table 4. The median time to enasidenib-related high-frequency PTs. PTs Median time IQR fatigue 69 29-132.75 nausea 21.5 6.75-51.5 diarrhoea 46 16-67 platelet count decreased 38 21-104.5 decreased appetite 31 13.75-63.75 differentiation syndrome 24 13-40 Subgroups analysis Gender group The top 20 PTs in gender subgroup are shown in Figure 2a, and the remaining PTs are detailed in Table S4. The results showed that there are twelve same PTs: nausea, fatigue, diarrhoea, differentiation syndrome, decreased appetite, asthenia, dyspnoea, full blood count decreased, weight decreased, dizziness, arthralgia, and blood bilirubin increased. The female group had eight different PTs: constipation, peripheral swelling, bone pain, pruritus, pain in extremity, weight increased, white blood cell count increased, dysgeusia, and abdominal discomfort. Meanwhile, the different PTs of the male group were as follows: vomiting, rash, fall, cough, red blood cell count decreased, headache, and taste disorder. Meanwhile, the time to onset of high-frequency PTs is detailed in Figure 2b. We also compared the occurrence of PTs in different sex groups, and the results showed no difference in the induction time between the different sex groups, as shown in Figure 2c. The median time to the female-related onset of PTs was 44 days (IQR 16-118 days), and 0-30 days, 31-60 days after medication accounted for 39.7% and 14.5%. At the same time, the median time to the male-related onset of PTs was 46 days (IQR 21-115 days), and 0-30 days, 31-60 days after medication accounted for 39.6% and 19.1%. 3.4.2 | Age group We compared PTs in different age groups, the statistically significant PTs in each subgroup are shown in Table 5. The group of 85 only had four PTs, the group of 18-64.9 had 19 PTs; however, the group of 65-85 had 48 PTs. Table 5. The statistically significant PTs of different age groups. Age groups PT case number ROR(95%Cl) IC(IC025) <18 acute febrile neutrophilic dermatosis 4 446.64 ( 101.49 - 1965.67 ) 7.45 ( 5.71 ) 18-64.9 pyrexia 19 1.72 ( 1.08 - 2.74 ) 0.75 ( 0.08 ) differentiation syndrome 18 23.98 ( 13.79 - 41.71 ) 4.08 ( 3.31 ) sepsis 15 2.36 ( 1.4 - 3.98 ) 1.18 ( 0.44 ) fatigue 14 5.73 ( 3.29 - 9.98 ) 2.38 ( 1.59 ) nausea 11 1.98 ( 1.08 - 3.64 ) 0.95 ( 0.09 ) asthenia 7 3.53 ( 1.64 - 7.62 ) 1.75 ( 0.69 ) decreased appetite 7 5.26 ( 2.42 - 11.46 ) 2.28 ( 1.21 ) dyspnoea 7 3.39 ( 1.57 - 7.29 ) 1.69 ( 0.63 ) bone pain 5 12.19 ( 4.63 - 32.07 ) 3.35 ( 2.05 ) haemoglobin abnormal 5 16.26 ( 6.01 - 43.95 ) 3.68 ( 2.36 ) full blood count decreased 5 5.85 ( 2.32 - 14.72 ) 2.42 ( 1.18 ) colitis 4 3.15 ( 1.15 - 8.65 ) 1.6 ( 0.26 ) fall 4 8.34 ( 2.92 - 23.87 ) 2.88 ( 1.49 ) taste disorder 4 46.75 ( 12.52 - 174.6 ) 4.71 ( 3.13 ) lymphadenopathy 3 14.58 ( 4.1 - 51.82 ) 3.56 ( 1.94 ) arthralgia 3 5.3 ( 1.62 - 17.33 ) 2.3 ( 0.77 ) neutrophil count abnormal 3 19.44 ( 5.25 - 72.02 ) 3.88 ( 2.23 ) white blood cell count abnormal 3 11.66 ( 3.37 - 40.41 ) 3.3 ( 1.71 ) staphylococcal sepsis 3 5.83 ( 1.77 - 19.16 ) 2.42 ( 0.89 ) 65-85 fatigue 55 3.39 ( 2.54 - 4.53 ) 1.58 ( 1.17 ) nausea 46 2.6 ( 1.91 - 3.55 ) 1.26 ( 0.81 ) platelet count decreased 42 1.4 ( 1.02 - 1.91 ) 0.45 ( -0.01 ) differentiation syndrome 41 19.08 ( 12.49 - 29.15 ) 3.37 ( 2.82 ) diarrhoea 33 1.9 ( 1.33 - 2.73 ) 0.86 ( 0.34 ) asthenia 27 1.79 ( 1.21 - 2.67 ) 0.78 ( 0.21 ) decreased appetite 26 3.33 ( 2.2 - 5.05 ) 1.58 ( 0.98 ) dyspnoea 23 2.57 ( 1.66 - 3.97 ) 1.25 ( 0.63 ) full blood count decreased 20 6.04 ( 3.66 - 9.94 ) 2.28 ( 1.58 ) blood bilirubin increased 12 5.87 ( 3.09 - 11.16 ) 2.26 ( 1.37 ) insomnia 12 10.53 ( 5.25 - 21.08 ) 2.87 ( 1.94 ) peripheral swelling 11 5.14 ( 2.65 - 9.96 ) 2.11 ( 1.19 ) cough 9 2.48 ( 1.24 - 4.97 ) 1.21 ( 0.25 ) white blood cell count increased 9 3.2 ( 1.59 - 6.47 ) 1.54 ( 0.56 ) pain 9 2.15 ( 1.08 - 4.27 ) 1.02 ( 0.06 ) renal failure 9 2.15 ( 1.08 - 4.27 ) 1.02 ( 0.06 ) headache 9 2.59 ( 1.29 - 5.18 ) 1.27 ( 0.3 ) eastern cooperative oncology group performance status worsened 9 63.08 ( 17.06 - 233.22 ) 4.04 ( 2.82 ) arthralgia 8 2.62 ( 1.26 - 5.48 ) 1.28 ( 0.26 ) haemoglobin abnormal 8 3.36 ( 1.59 - 7.09 ) 1.6 ( 0.56 ) weight increased 6 12.59 ( 4.57 - 34.69 ) 3.04 ( 1.74 ) somnolence 6 6.29 ( 2.52 - 15.69 ) 2.34 ( 1.11 ) bone pain 5 7.49 ( 2.69 - 20.82 ) 2.53 ( 1.18 ) hyperleukocytosis 5 8.74 ( 3.08 - 24.83 ) 2.69 ( 1.33 ) neutrophil count abnormal 5 6.17 ( 2.27 - 16.74 ) 2.32 ( 0.99 ) platelet count abnormal 5 4.56 ( 1.73 - 12 ) 1.97 ( 0.67 ) adverse event 5 6.99 ( 2.54 - 19.26 ) 2.45 ( 1.12 ) blood potassium decreased 4 3.81 ( 1.31 - 11.07 ) 1.75 ( 0.35 ) rash pruritic 4 5.59 ( 1.85 - 16.86 ) 2.21 ( 0.76 ) depression 4 2.99 ( 1.05 - 8.54 ) 1.45 ( 0.07 ) haemoptysis 4 3.35 ( 1.17 - 9.64 ) 1.6 ( 0.2 ) haematemesis 3 3.49 ( 1.03 - 11.86 ) 1.65 ( 0.08 ) urticaria 3 6.28 ( 1.73 - 22.86 ) 2.34 ( 0.7 ) gallbladder disorder 3 5.71 ( 1.59 - 20.5 ) 2.23 ( 0.61 ) dry mouth 3 7.86 ( 2.08 - 29.64 ) 2.58 ( 0.91 ) mouth haemorrhage 3 4.83 ( 1.38 - 16.98 ) 2.04 ( 0.43 ) chest discomfort 3 4.83 ( 1.38 - 16.98 ) 2.04 ( 0.43 ) muscle spasms 3 3.93 ( 1.14 - 13.49 ) 1.79 ( 0.21 ) blood pressure increased 3 3.7 ( 1.08 - 12.62 ) 1.72 ( 0.14 ) joint swelling 3 4.19 ( 1.21 - 14.48 ) 1.87 ( 0.28 ) hypoaesthesia 3 4.83 ( 1.38 - 16.98 ) 2.04 ( 0.43 ) blood uric acid increased 3 5.24 ( 1.48 - 18.58 ) 2.13 ( 0.52 ) taste disorder 3 5.24 ( 1.48 - 18.58 ) 2.13 ( 0.52 ) gout 3 3.49 ( 1.03 - 11.86 ) 1.65 ( 0.08 ) arthritis 3 6.98 ( 1.89 - 25.82 ) 2.45 ( 0.8 ) myositis 3 10.48 ( 2.62 - 41.92 ) 2.87 ( 1.16 ) blood disorder 3 3.7 ( 1.08 - 12.62 ) 1.72 ( 0.14 ) swelling 3 4.83 ( 1.38 - 16.98 ) 2.04 ( 0.43 ) >85 fatigue 6 3.11 ( 1.27 - 7.6 ) 1.42 ( 0.22 ) diarrhoea 5 3.94 ( 1.46 - 10.64 ) 1.71 ( 0.38 ) nausea 4 4.11 ( 1.35 - 12.49 ) 1.77 ( 0.31 ) decreased appetite 4 9.44 ( 2.72 - 32.72 ) 2.63 ( 1.07 ) We also compared the occurrence of PTs in different age groups, as shown in Figure 2d. As shown in Table 6 The median time to the four age groups was 115 days (IQR 115-115 days), 40 days (IQR 13-109.5 days),43 days (IQR 17-124 days), and 48 days (IQR 28-93 days), respectively. And 0-30 days after medication of 18-64.9, 65-85, and > 85 accounted for 42.3%, 38.7%, and 31.8%, respectively. Table 6. Onset of PTs induced by enasidenib in different age groups. Group(years) 18-64.9 65-85 >85 days case number percentage% case number percentage% case number percentage% 0-30 days 69 42.3% 160 38.7% 7 31.8% 31-60 days 28 17.2% 70 16.9% 5 22.7% 61-90 days 14 8.6% 42 10.2% 5 22.7% 91-120 days 12 7.4% 27 6.5% 1 4.5% 121-150 days 6 3.7% 19 4.6% 0 0.0% 151-180 days 7 4.3% 19 4.6% 0 0.0% 181-360 days 16 9.8% 35 8.5% 1 4.5% >360 days 11 6.7% 41 9.9% 3 13.6% Discussion Our study showed a higher rate of AEs reported in men than women, probably because of the increasing population diagnosed with AML in males [29], consequently causing more medication opportunities. However, the median onset of all the AEs between male and female patients was almost indistinctive, primarily about 6 to 7 weeks. What's more, our study revealed a high ratio of AEs in elderly patients (>65 years old), potentially due to the increased AML incidence with age, especially among individuals over 65 years old [6, 29]. Elderly patients are more likely to have a comorbid illness, decreased tissue/organ tolerance to drugs, and impaired organ function, hinting at more occurrence of AEs [30]. Patients aged 65-85 mined the most number of PTs. Furthermore, the median time of the incidence of AEs among all the age groups was a little bit different, the median time in patients under age 18 was the longest, while the median time in other age groups was similar, almost about 6 to 7 weeks. Medical professionals accounted for 63.4% of AE reporters, with reporting almost concentrated in the United States and France. Besides, the number of reported AEs gradually increased from 2017 to 2020, then fell from 2020 to 2024. The use of enasidenib may lead to serious AEs, with approximately 54.8% of reported cases resulting in hospitalization, death, life-threatening, and disability. Our results revealed that enasidenib produces a high incidence of death, so close attention should be paid to AEs, especially serious AEs. In this study, 78 PTs involving 17 SOCs were identified to be related to enasidenib-induced AEs. High-frequency SOCs were basically detected in reactions for instance investigations, gastrointestinal disorders, general disorders and administration site conditions, and nervous system disorders, consistent with the previous findings of enasidenib [25, 31]. Investigations with high frequency of occurrence include platelet count decreased, full blood cell count decreased, weight decreased, blood bilirubin increased, etc. Thrombocytopenia was reported as one of the most common AEs in clinical trials [32, 33]. Our study showed the median onset of platelet count decreased was about 5 weeks. As serious platelet count decreases mainly causes bleeding, but thrombosis sometimes [34], it is important to monitor the platelet count and the blood coagulation function in the first two months. Although full blood cell count decreased was not mentioned on the drug label, our study observed a high frequency of occurrence, suggesting the necessity of the routine monitoring of blood cell count. However, weight decrease was mentioned as a symptom related to gastrointestinal disorders in the description. Weight change fast in a short time may reflect the efficiency of the treatment [35], indicating the importance of weight monitoring during medication. Enasidenib may interfere with bilirubin metabolism [36], thus patients would experience elevated liver enzymes or hyperbilirubinemia. Despite the few patients need dose reduction for hyperbilirubinemia, it is still essential to periodically monitor liver enzymes and bilirubin as hyperbilirubinemia generally decreases in frequency with enasidenib treatment continued, but persistent bilirubin elevation may lead to treatment termination [36]. Besides, SOC in investigations and blood and lymphatic system disorders, mined PTs similar to leukocytosis such as white blood cell count increased and hyperleukocytosis. Noninfectious leukocytosis is a risk factor for dosage modifications during medications of enasidenib. It may be related to rapid myeloid proliferation, manifested by leukocytosis [37], usually, there are no clinical signs of infection or differentiation syndrome (DS) concurrently exist. If the patient taking enasidenib was diagnosed with noninfectious leukocytosis, initiating hydroxyurea can improve [38]. There is a high frequency of occurrence in gastrointestinal disorders related to enasidenib, such as nausea, diarrhoea, and constipation, consistent with the drug label and clinical trials [39-41]. Females may pay attention to constipation, and males take notice of vomiting. According to the subgroup analysis, it is interesting to know that nausea occurs earlier than diarrhoea, as the median onset of nausea is about 3 weeks and diarrhoea is about 6 weeks. The general disorders and administration site conditions with a high frequency of occurrence include fatigue, asthenia, and peripheral swelling. However, fatigue was commonly reported in clinical trials [17] instead of the instruction manual. The median onset of fatigue was a little long, about 2 months after medication. Peripheral swelling with weight rapid gained may be associated with DS, thus close attention should be paid during medication. We observed a significant increase in the signal intensity of AEs related to nervous system disorders including dizziness, headache, taste disorder, and somnolence, these AEs are not explicitly mentioned in the manual except for dysgeusia. Dizziness, headache, and taste disorder are the top 20 PTs of enasidenib. To our knowledge, dizziness and somnolence have not been reported in any research yet. This suggests clinicians paying attention to the AEs in nervous system is necessary. It is worth noting that enasidenib is linked to musculoskeletal and connective tissue disorders, which include arthralgia, bone pain, pain in extremity, and joint swelling. However, these AEs are not explicitly mentioned in the manual but in a retrospective study [42], bone pain/arthralgia were reported as signs and symptoms of DS. For PTs detected in respiratory, thoracic and mediastinal disorders such as dyspnoea and cough are significantly high. Dyspnoea is one of the signs and symptoms of DS, it also has a higher frequency of occurrence, so more attention is needed to early diagnosis and management. Metabolism and nutrition disorders are frequent AEs of enasidenib, and include decreased appetite which has been noted on the drug label, is one of the most common and serious AEs for reducing patients’ medication compliance. Decreased appetite may reduce nutrition and energy intake, while the reduction in energy intake may lead to subclinical deficits that directly affect the immunity function in the elderly [43]. The median onset of decreased appetite is about 4 weeks, quite close to the median onset of DS. DS has a high frequency of occurrence in malignant and unspecified. It is primarily reported in clinical studies and instruction manuals [3, 24, 25, 31, 36]. It is of course a common and potentially fatal AEs of enasidenib that is listed as a boxed warning in the package insert. DS may often result in discontinuation or dose reduction of the medications in patients [44, 45]. The occurrence identified with DS was 1.92%, ranking 6 th . DS occurs as early as 1 day and up to 3-5 months after administration, the median time to onset is 10-30 days [23, 38, 42, 46], as reported. Our results showed that the median onset of DS is 24 days. Therefore, special attention should be paid if the patient develops symptoms such as fever, dyspnea, peripheral edema with rapid weight gain, decreased appetite, especially in the first month of taking enasidenib, as they may induce severe AEs, even death. As a response to DS, corticosteroid therapy needs to be initiated and hemodynamic monitoring [45]. Unexpected and significant safety SOCs, such as surgical and medical procedures, psychiatric disorders, injury, poisoning and procedural complications, skin and subcutaneous tissue disorders, immune system disorders, infections and infestations, were mined in our study. PTs in surgical and medical procedures were mined significantly related to enasidenib such as hospitalization. As previously mentioned, enasidenib may induce a relatively high rate of hospitalization and death, once patients develop dyspnoea or symptoms of DS, early professional medication is urgent and helpful. PTs in psychiatric disorders including insomnia, anxiety, and depression were identified, suggesting that clinicians and family members should pay attention to the mental state of the patients during medications. Our study also observed PTs in injury, poisoning and procedural complications, mainly including falls, this AE is also an unexpected adverse reaction of enasidenib. It is reported that 33% of older adults fall every year [47, 48]. The incidence of falls may associated with the use of drugs, primarily because of side effects such as dizziness, balance disorders or asthenia, etc. [49]. In all, if a patient develops AEs such as dizziness or asthenia during the medication, it is necessary to remind the risk of falls. It is a concern about skin and subcutaneous tissue disorders, such as pruritus and acute febrile neutrophilic dermatosis, although the number of PTs is not so big, are not explicitly mentioned in the manual. The mechanism of pruritus secondary to enasidenib is still unknown. Parisi R et. al [50], found that pruritus was a common dermatologic adverse event(DAE), and the median onset was 53 days. Even if associated DAE do not increase mortality, they could reduce the quality of life and the tolerance of treatment in patients with AML. Thus, early identification and symptomatic management of DAE are very necessary, especially during the first 2 months of initiations. Acute febrile neutrophilic dermatosis, usually concurrently with neutrophilic inflammatory infiltrate may be similar to the symptoms of infections [1,51]. In addition, a few PTs in immune system disorders and infections and infestations were detected, including seasonal allergy, nasopharyngitis, and coronavirus infection. However, these AEs are not explicitly mentioned in the manual. Similar situations are also shown in renal and urinary disorders, such as renal disorder, pollakiuria, nephrolithiasis, and chromaturia. So it is also important to monitor the function of the kidney during medications. To improve the prognosis of the above-mentioned AEs, early diagnosis, proper treatment, and prevention are important and necessary. Meanwhile, we found different PTs among males and females, as shown in Figure 2. No matter what the gender is the patient, AEs like nausea, fatigue, decreased appetite, diarrhoea, etc, may occur during the initiation of enasidenib. Males are more likely to experience AEs such as vomiting, falls, and cough while AEs like constipation, peripheral swelling, and bone pain occur more often in females. Based on this, clinicians could take different management and drug education according to gender. The number of AEs increased gradually as the age increased to 85, and patients aged 65-85 mined the most number of AEs. This is consistent with the occurrence of AML, as the number of patients diagnosed with AML is increasing with age, especially at age 65 and above [8]. Since the use of enasidenib in groups of children is an off-label use, the safety among this population is uncertain. Due to the fact that older patients aged 60 and above were more often developing multiple comorbidities [52], it is needed to be more cautious. As the results shown in Table 5, populations aged 18-64.9 were more commonly to take place AEs such as pyrexia, sepsis, and colitis, while AEs like platelet count decreased, diarrhoea, and peripheral swelling, primarily occurred more often in patients aged 65-85. However, AEs for instance DS, nausea, fatigue, asthenia, decreased appetite, dyspnoea, full blood count decreased, and blood bilirubin increased, were both commonly detected among populations aged 18-85. The median time for detecting AEs with enasidenib was 47 days (IQR 18-118 days), and more than 54% of AEs occurred within 60 days. The median onset of nausea, decreased appetite and DS were within the first month, while platelet count decreased and diarrhoea were 5-7 weeks after medication. According to these results, it is recommended that longer follow-up periods will be required in future clinical studies to monitor AEs. Conclusion Our study analyzed AEs signals associated with enasidenib based on the FAERS to enhance clinical medication safety. The AEs identified in this study largely align with those documented in the enasidenib's manual. Additionally, we uncovered AEs not previously listed, including fatigue, asthenia, platelet count decreased, full blood count decreased, dizziness, constipation, etc. These findings supplement the limited sample size of pre-market clinical studies of enasidenib. Gender-specific and age-specific patients should be concerned about the occurrence of appropriate AEs. However, the FAERS is a spontaneous reporting system with significant reporting bias (selective and underreporting) and has missing data. And we have not yet explored the correlation between AEs and the drug itself, underscoring the need to augment safety information. Further research is still warranted to elucidate the relationship between AEs and enasidenib. Declarations Ethics approval Since FEARs is a public database, this study does not require ethics committee approval. None. Conflict and interest The authors declare no competing interests. Data availability statement: The original contributions presented in the study are included in the article or Supplementary Materials, further inquiries can be directed to the corresponding author. Author contributions All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, J.X., Q.G., and Y.C. designed the research; J.X., Q.G., performed the analyses; J.X. and L.X., and Y.Q. collected and interpreted data; J.X. and Q.G. wrote the paper; J.X., QG., L.X., Y.Q., and Y.C. critically revised the paper; L.X. and Y.C. final approved of the version to be published. All authors contributed to the article and approved the submitted version. References Ayyash, A. M. & Sampath, R. Acute Febrile Neutrophilic Dermatosis. NEW. ENGL. J. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6698707","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":500713726,"identity":"421b1997-9818-451a-8b70-8cdd30cc7539","order_by":0,"name":"Jiangchuan Xie","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiangchuan","middleName":"","lastName":"Xie","suffix":""},{"id":500713727,"identity":"940e23cd-5afa-45b8-9de3-d220791dcdb2","order_by":1,"name":"Qian Gao","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Gao","suffix":""},{"id":500713728,"identity":"e9fa0869-803b-4554-ba98-cf1e8af4c61a","order_by":2,"name":"Yu Qin","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yu","middleName":"","lastName":"Qin","suffix":""},{"id":500713729,"identity":"657e3f3e-a59a-4b84-844a-7189e8dc5f44","order_by":3,"name":"Linli XIE","email":"","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":false,"prefix":"","firstName":"Linli","middleName":"","lastName":"XIE","suffix":""},{"id":500713730,"identity":"af7a4e4f-cf04-4837-9282-3f6a3a45605b","order_by":4,"name":"Yongchuan Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvUlEQVRIiWNgGAWjYPACGyjNRryWNAmStRwmQYv8jOzEzzw15+t0p50xYPhQdpiBf3YDfi2MM3I3S/Mcuy1hdjvHgHHGucMMEncO4NfCLJ27jZm3AaKFmbftMIOBRAJ+LWwQLecgWv4So4UHouUARAsjMVok5N9ulpxzLFly2+20goM959J5JG4Q0CLfc3bjhzc1dvxmt5M3PvhRZi3HP4OAFhBg4oEyDoBcSlg9EDD+IErZKBgFo2AUjFgAANFJPs4znG/rAAAAAElFTkSuQmCC","orcid":"","institution":"The First Affiliated Hospital of Army Medical University","correspondingAuthor":true,"prefix":"","firstName":"Yongchuan","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-05-19 11:53:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6698707/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6698707/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89560416,"identity":"f6a9028f-b7a7-4a09-bc7d-4129f9e37094","added_by":"auto","created_at":"2025-08-21 10:19:16","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1636962,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTime to onset of enasidenib-related PTs.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6698707/v1/04ef0c0313769c31bf52a5d4.jpg"},{"id":89560417,"identity":"1c2860b6-348a-472e-8553-a9e0f9c91afe","added_by":"auto","created_at":"2025-08-21 10:19:16","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":6302712,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults of Subgroups. a. The top 20 PTs of female group and male group;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb. Time to onset of enasidenib-related high-frequency PTs; c. Onset of PTs induced by enasidenib in different gender groups; d. Onset of PTs induced by enasidenib in different age groups.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6698707/v1/eb8e211d5f01a75576ec5fd2.jpg"},{"id":107535356,"identity":"ec21c061-c522-417e-ab48-590865cfe99b","added_by":"auto","created_at":"2026-04-22 11:12:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":9054256,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6698707/v1/9b5b0330-4104-4f29-a0f7-1da49f0be00c.pdf"},{"id":89560413,"identity":"fccd3b13-eaee-47ba-8e8f-733cbfdac256","added_by":"auto","created_at":"2025-08-21 10:19:16","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":78909,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData20250519.docx","url":"https://assets-eu.researchsquare.com/files/rs-6698707/v1/2fb75358a38e07e89a927c24.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk factors and subgroups analysis of Enasidenib in treating Acute Myelogenous Leukemia : a pharmacovigilance study based on FAERS database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLeukemias are a category of life-threatening haematological malignancies, with significant morbidity and mortality [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, the number of patients diagnosed with AML in the United States, China, and India in 2021 was 21533,17835 and 11040, respectively[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. What\u0026rsquo;s more, AML occurs more often in older adults, especially at age 65 and over [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The routine treatment process for AML includes: chemotherapy, conventional, and allogeneic hematopoietic stem cell transplant(allo-HSCT) [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, chemotherapy has significant side effects [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and conventional targeted therapy is prone to drug resistance [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Furthermore, allo-HSCT is not a once-for-all approach as almost 50% of patients relapse and the risk of non-relapse mortality is high [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Thus, new exploration has never stopped.\u003c/p\u003e\u003cp\u003eIn recent years, more than 95% of detectable somatic mutations in patients with AML have been found [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Of them, mutations on isocitrate dehydrogenase have been detected in multiple tumors [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], while AML, accounts for 20%. These findings open up new tracks for the treatment of AML. Enasidenib is an orally small molecule of IDHI-2, originally approved for the treatment of adult patients with IDH2-mutated AML in 2017 by the Food and Drug Administration (FDA). It is reported that enasidenib significantly improved the rate of complete response/complete response with incomplete count recovery (CR/CRi) and prolonged the median overall survival in patients with R/R AML [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Numerous studies showed good tolerance of enasidenib in patients with IDH2-mutated AML [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlong with its extensive usage, the number of reported AEs also increased. So, it is essential to pay close attention to its latent AEs. Previously reported AEs were mainly derived from clinical trials, which may differ from the real-world population. Therefore, it is quite necessary to research the safety of enasidenib based on the postmarketing world data.\u003c/p\u003e\u003cp\u003eThe FDA Adverse Event Reporting System (FAERS) is a public free spontaneous pharmacovigilance database [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], that contains a large number of real-world safety signals data which may have been ignored in clinical studies. This study aims to identify and characterize AEs significantly related to enasidenib in treating AML and to provide valuable clinical references.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData source\u003c/h2\u003e\u003cp\u003eOur study collected enasidenib\u0026rsquo; AEs data from the FAERS Quarterly Data Extract Files between the third quarter of 2017 (FDA marketing approval of enasidenib for the treatment of AML) and the third quarter of 2024.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDrug identification\u003c/h3\u003e\n\u003cp\u003eReports involving enasidenib for AML. During the data mining process, they were identified in the FAERS by brand and generic name.\u003c/p\u003e\n\u003ch3\u003eRegression analysis\u003c/h3\u003e\n\u003cp\u003eAs shown in Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e, we assessed the relationship between AEs and enasidenib using the Proportional Reporting Ratio (PRR) and Bayesian confidence propagation neural network(BCPNN) using the contingency table calculator from Open Vigil. A risk signal was considered when the lower limit of the corresponding 95% CI was \u0026gt;\u0026thinsp;1, a\u0026thinsp;\u0026gt;\u0026thinsp;3, and IC-2SD\u0026gt;0. Table S2 shows the calculation formula. Data were analyzed using MYSQL (version 8.0) and R studio software (version 9.1.0).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eBaseline characteristics of enasidenib\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, for the treatment of AML, a total of 2098 AE reports were retrieved. In terms of gender, reports for males were higher than females(40.5% for female, 53.0% for male). As for age composition, the highest proportion is 65-85 years old (39.3%).\u0026nbsp;In 2020, the number of reported AEs is the highest (23.1%). What\u0026apos;s more, hospitalization was the most common outcome for enasidenib (26.5% ), and the proportion of deaths is relatively high(25.5%). The United States, and France reported the highest number of AEs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Characteristics of reports-all reports for enasidenib (Q3 2017 to Q3 2024).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eItems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 56px;\"\u003e\n \u003cp\u003eCase number=2098\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100px;\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e849\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e40.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eMale\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e1111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e53.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eUknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e6.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100px;\"\u003e\n \u003cp\u003eWeight\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e＜50 kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e1.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e50～100 kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e17.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e＞100 kg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e1.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e1675\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e79.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003e＜18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e0.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e18～64.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e15.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e65～85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e825\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e39.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e\u0026gt;85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e2.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e886\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e42.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 100px;\"\u003e\n \u003cp\u003eReporter\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eCustomer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e17.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eHealth Professional\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e527\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e25.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eMedical Doctor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e28.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e395\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e18.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003ePharmacists\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e9.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 43px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e0.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 100px;\"\u003e\n \u003cp\u003eReporting country\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003eThe United States\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e1604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e76.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e6.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 25px;\"\u003e\n \u003cp\u003e365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e17.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003eYears\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e3.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e318\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e15.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e376\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e17.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e485\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e23.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e338\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e16.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e9.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e5.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e179\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e8.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eHospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e555\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e26.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eDeath\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e25.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eLife-threatening\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e2.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eDisability\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e0.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 43px;\"\u003e\n \u003cp\u003eOther serious outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e11.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 43px;\"\u003e\n \u003cp\u003eMissing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 25px;\"\u003e\n \u003cp\u003e715\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e34.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisproportionality analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, the disproportionality at the system organ class (SOC) level of enasidenib was observed. AEs presented eight areas of toxicity: gastrointestinal disorders, general disorders and administration site conditions, investigations, metabolism and nutrition disorders, musculoskeletal and connective tissue disorders, neoplasms benign, malignant and unspecified, nervous system disorders, and psychiatric disorders.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Signal strength of reports of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eenasidenib\u0026nbsp;at the system organ class (SOC) level in the FAERS database.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"104%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003eIC(IC025)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.36 ( 0.31 - 0.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.32 ( -1.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003ecardiac disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.41 ( 0.31 - 0.55 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.24 ( -1.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003econgenital, familial and genetic disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.15 ( 0.02 - 1.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-2.67 ( -4.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eear and labyrinth disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.83 ( 0.31 - 2.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.26 ( -1.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eendocrine disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.55 ( 0.18 - 1.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.84 ( -2.3 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eeye disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.79 ( 0.49 - 1.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.33 ( -1.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*gastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.65 ( 1.48 - 1.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.63 ( 0.48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*general disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e861\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.48 ( 1.37 - 1.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.44 ( 0.33 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003ehepatobiliary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.55 ( 0.39 - 0.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.84 ( -1.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003einfections and infestations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.63 ( 0.56 - 0.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.58 ( -0.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e172\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.53 ( 0.45 - 0.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.85 ( -1.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.45 ( 0.3 - 0.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.1 ( -1.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*investigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e522\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.33 ( 1.21 - 1.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.35 ( 0.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*metabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e136\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.55 ( 1.3 - 1.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.59 ( 0.33 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*musculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e122\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e2.19 ( 1.82 - 2.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.05 ( 0.78 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*neoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.39 ( 1.22 - 1.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.43 ( 0.24 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*nervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.69 ( 1.47 - 1.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.69 ( 0.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003erenal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.93 ( 0.72 - 1.19 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.11 ( -0.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.13 ( 0.93 - 1.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.16 ( -0.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e1.11 ( 0.95 - 1.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.14 ( -0.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003evascular disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.86 ( 0.66 - 1.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-0.2 ( -0.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003e*psychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e2.01 ( 1.57 - 2.57 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.95 ( 0.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003esocial circumstances\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.38 ( 0.09 - 1.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.37 ( -3.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.42 ( 0.32 - 0.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.2 ( -1.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 47px;\"\u003e\n \u003cp\u003ereproductive system and breast disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e0.37 ( 0.09 - 1.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19px;\"\u003e\n \u003cp\u003e-1.41 ( -3.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*indicates statistically significant signals in the algorithm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAbbreviations: ROR, reporting odds ratio; CI, confidence interval.\u003c/p\u003e\n\u003cp\u003eThere are 78 positive signal different preferred terms (PTs) in at least 3 cases. Table 3 lists the number of PTs for each corresponding SOC, and others are described in Table S3. Interestingly, among the 78 PTs, 52 were uncovered in the drug label, such as fatigue, asthenia, platelet count decreased, full blood count decreased, dizziness, constipation, etc.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Positive signal of the preferred term (PT) and the clinical priority assessing results.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"105%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003eSOC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003eCase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003eIC(IC025)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eblood and lymphatic system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ehyperleukocytosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.75 ( 1.7 - 8.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.77 ( 0.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ethrombocytosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.2 ( 1.79 - 15.17 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.18 ( 0.77 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 23px;\"\u003e\n \u003cp\u003egastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003enausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.86 ( 2.36 - 3.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.4 ( 1.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ediarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.35 ( 1.89 - 2.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.15 ( 0.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*constipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e1.82 ( 1.27 - 2.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.82 ( 0.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eabdominal pain upper\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.95 ( 1.7 - 5.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.46 ( 0.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eabdominal discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.65 ( 2.09 - 6.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.74 ( 0.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*dry mouth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.6 ( 1.41 - 9.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.72 ( 0.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" 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: 27px;\"\u003e\n \u003cp\u003e*fatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.85 ( 3.2 - 4.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.77 ( 1.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*asthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.05 ( 1.56 - 2.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.97 ( 0.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eperipheral swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.26 ( 2.74 - 6.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.93 ( 1.3 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*feeling abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.28 ( 1.11 - 4.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.12 ( 0.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*influenza like illness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.31 ( 1.28 - 14.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.95 ( 0.38 )\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: 27px;\"\u003e\n \u003cp\u003egallbladder disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.31 ( 1.28 - 14.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.95 ( 0.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eimmune system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*seasonal allergy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e20.49 ( 4.58 - 91.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.6 ( 1.83 )\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: 27px;\"\u003e\n \u003cp\u003e*nasopharyngitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.99 ( 1.37 - 6.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.48 ( 0.4 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*coronavirus infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.31 ( 1.28 - 14.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.95 ( 0.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 23px;\"\u003e\n \u003cp\u003einjury, poisoning and procedural complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*fall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e1.91 ( 1.26 - 2.89 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.88 ( 0.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*transfusion reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.56 ( 1.07 - 11.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.71 ( 0.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"18\" style=\"width: 23px;\"\u003e\n \u003cp\u003einvestigations\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*platelet count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e1.31 ( 1.05 - 1.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.37 ( 0.04 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*full blood count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e6.15 ( 4.58 - 8.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.37 ( 1.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eweight decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.45 ( 2.31 - 5.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.66 ( 1.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eblood bilirubin increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.31 ( 2.83 - 6.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.94 ( 1.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*red blood cell count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.47 ( 1.61 - 3.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.23 ( 0.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ewhite blood cell count increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.59 ( 1.6 - 4.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.29 ( 0.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*haemoglobin abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.25 ( 1.93 - 5.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.58 ( 0.85 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eweight increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.32 ( 1.87 - 5.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.62 ( 0.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*eastern cooperative oncology group performance status worsened\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e82.16 ( 26.49 - 254.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4.41 ( 3.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eneutrophil count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e6.14 ( 3.19 - 11.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.38 ( 1.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eplatelet count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.08 ( 1.54 - 6.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.52 ( 0.55 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ewhite blood cell count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.35 ( 1.14 - 4.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.16 ( 0.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eblood potassium decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.48 ( 1.15 - 5.39 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.24 ( 0.17 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*blood pressure decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.42 ( 1.46 - 7.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.65 ( 0.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eliver function test increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.22 ( 1.38 - 7.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.58 ( 0.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003eblood uric acid increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.97 ( 2.08 - 11.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.12 ( 0.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*full blood count increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e13.66 ( 3.42 - 54.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.24 ( 1.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*bone marrow myelogram abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e10.25 ( 2.72 - 38.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.95 ( 1.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 23px;\"\u003e\n \u003cp\u003emetabolism and nutrition disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003edecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.33 ( 4.18 - 6.78 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.19 ( 1.84 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*gout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.25 ( 1.29 - 8.23 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.59 ( 0.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"11\" style=\"width: 23px;\"\u003e\n \u003cp\u003emusculoskeletal and connective tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*arthralgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.74 ( 1.73 - 4.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.36 ( 0.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ebone pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e6.45 ( 3.74 - 11.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.43 ( 1.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*pain in extremity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.04 ( 1.18 - 3.51 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.97 ( 0.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*joint swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e9.13 ( 4.74 - 17.55 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.82 ( 1.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*muscular weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.23 ( 1.08 - 4.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.1 ( 0.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*musculoskeletal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.56 ( 1.77 - 11.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.02 ( 0.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*arthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4.41 ( 1.71 - 11.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.97 ( 0.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*back disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e13.66 ( 4.11 - 45.4 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.24 ( 1.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*neck pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.73 ( 1.11 - 12.45 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.76 ( 0.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*musculoskeletal stiffness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.9 ( 1.16 - 13.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.82 ( 0.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*myositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.9 ( 1.16 - 13.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.82 ( 0.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003eneoplasms benign, malignant and unspecified (incl cysts and polyps)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003edifferentiation syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e13.9 ( 10.53 - 18.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.24 ( 2.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"12\" style=\"width: 23px;\"\u003e\n \u003cp\u003enervous system disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*dizziness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.59 ( 1.79 - 3.75 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.29 ( 0.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*headache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e1.76 ( 1.13 - 2.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.78 ( 0.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003etaste disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e13.71 ( 7.9 - 23.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.24 ( 2.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003edysgeusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e12.84 ( 6.95 - 23.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.18 ( 2.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*somnolence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.77 ( 2.06 - 6.91 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.78 ( 0.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*neuropathy peripheral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.86 ( 1.44 - 5.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.42 ( 0.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*paraesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.54 ( 1.61 - 7.79 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.7 ( 0.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*hypersomnia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e7.81 ( 3.15 - 19.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.65 ( 1.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*hypoaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e4 ( 1.7 - 9.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.85 ( 0.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*balance disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.73 ( 1.09 - 6.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.36 ( 0.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*ageusia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e6.43 ( 2.16 - 19.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.43 ( 1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*dementia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.46 ( 1.58 - 18.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.24 ( 0.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 23px;\"\u003e\n \u003cp\u003epsychiatric disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*insomnia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.06 ( 3.01 - 8.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.14 ( 1.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*sleep disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e6.83 ( 2.56 - 18.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.5 ( 1.19 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*depressed mood\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.8 ( 1.49 - 9.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.79 ( 0.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 23px;\"\u003e\n \u003cp\u003erenal and urinary disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003erenal disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.37 ( 1.2 - 4.68 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.17 ( 0.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*pollakiuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.69 ( 2.17 - 14.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.29 ( 1 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*nephrolithiasis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e5.75 ( 1.96 - 16.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.3 ( 0.88 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*chromaturia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e7.29 ( 2.42 - 21.97 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.58 ( 1.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 23px;\"\u003e\n \u003cp\u003erespiratory, thoracic and mediastinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003edyspnoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.94 ( 2.2 - 3.93 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.45 ( 1.03 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003ecough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.74 ( 1.77 - 4.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.36 ( 0.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*rhinorrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e7.19 ( 2.68 - 19.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e2.56 ( 1.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*chronic obstructive pulmonary disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e3.42 ( 1.35 - 8.66 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.65 ( 0.4 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*upper-airway cough syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e27.32 ( 5.51 - 135.42 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3.82 ( 2.01 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 23px;\"\u003e\n \u003cp\u003eskin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*pruritus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.21 ( 1.39 - 3.54 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.08 ( 0.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*acute febrile neutrophilic dermatosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e2.45 ( 1.13 - 5.32 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e1.22 ( 0.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23px;\"\u003e\n \u003cp\u003esurgical and medical procedures\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 27px;\"\u003e\n \u003cp\u003e*hospitalisation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 14px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e1.79 ( 1.33 - 2.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e0.79 ( 0.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*indicates unexpected AEs in the algorithm.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTime-to-onset analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe time from enasidenib use to AEs occurrence was assessed and shown in Figure 1. The median time to the AEs was 46 days (IQR 17-118 days), and 0-30 days, 31-60 days after medication accounted for 38.2% and 16.5%. And Table 4 showed the median time to high-frequency PTs\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. The median time to enasidenib-related high-frequency PTs.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003ePTs\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003eMedian time\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39px;\"\u003e\n \u003cp\u003efatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e29-132.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39px;\"\u003e\n \u003cp\u003enausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e21.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e6.75-51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39px;\"\u003e\n \u003cp\u003ediarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e16-67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 39px;\"\u003e\n \u003cp\u003eplatelet count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e21-104.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39px;\"\u003e\n \u003cp\u003edecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e13.75-63.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 39px;\"\u003e\n \u003cp\u003edifferentiation syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 29px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e13-40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroups analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGender group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe top 20 PTs in gender subgroup are shown in Figure 2a, and the remaining PTs are detailed in Table S4. The results showed that there are twelve same PTs: nausea, fatigue, diarrhoea, differentiation syndrome, decreased appetite, asthenia, dyspnoea, full blood count decreased, weight decreased, dizziness, arthralgia, and blood bilirubin increased. The female group had eight different PTs: constipation, peripheral swelling, bone pain, pruritus, pain in extremity, weight increased, white blood cell count increased, dysgeusia, and abdominal discomfort. Meanwhile, the different PTs of the male group were as follows: vomiting, rash, fall, cough, red blood cell count decreased, headache, and taste disorder. Meanwhile, the time to onset of high-frequency PTs is detailed in Figure 2b.\u003c/p\u003e\n\u003cp\u003eWe also compared the occurrence of PTs in different sex groups, and the results showed no difference in the induction time between the different sex groups, as shown in Figure 2c. The median time to the female-related onset of PTs was 44 days (IQR 16-118 days), and 0-30 days, 31-60 days after medication accounted for 39.7% and 14.5%. At the same time, the median time to the male-related onset of PTs was 46 days (IQR 21-115 days), and 0-30 days, 31-60 days after medication accounted for 39.6% and 19.1%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3.4.2\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e|\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAge group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe compared PTs in different age groups, the statistically significant PTs in each subgroup are shown in Table 5. The group of \u0026lt;18 only had one PT and the group of \u0026gt;85 only had four PTs, the group of 18-64.9 had 19 PTs; however, the group of 65-85 had 48 PTs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 5. The statistically significant PTs of different age groups.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003eAge groups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ePT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003eROR(95%Cl)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003eIC(IC025)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026lt;18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eacute febrile neutrophilic dermatosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e446.64 ( 101.49 - 1965.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e7.45 ( 5.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"19\" style=\"width: 13px;\"\u003e\n \u003cp\u003e18-64.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003epyrexia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1.72 ( 1.08 - 2.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.75 ( 0.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edifferentiation syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e23.98 ( 13.79 - 41.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4.08 ( 3.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003esepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.36 ( 1.4 - 3.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.18 ( 0.44 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.73 ( 3.29 - 9.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.38 ( 1.59 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003enausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1.98 ( 1.08 - 3.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.95 ( 0.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003easthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.53 ( 1.64 - 7.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.75 ( 0.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.26 ( 2.42 - 11.46 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.28 ( 1.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edyspnoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.39 ( 1.57 - 7.29 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.69 ( 0.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ebone pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e12.19 ( 4.63 - 32.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.35 ( 2.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehaemoglobin abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e16.26 ( 6.01 - 43.95 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.68 ( 2.36 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efull blood count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.85 ( 2.32 - 14.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.42 ( 1.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ecolitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.15 ( 1.15 - 8.65 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.6 ( 0.26 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efall\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e8.34 ( 2.92 - 23.87 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.88 ( 1.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003etaste disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e46.75 ( 12.52 - 174.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4.71 ( 3.13 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003elymphadenopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e14.58 ( 4.1 - 51.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.56 ( 1.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003earthralgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.3 ( 1.62 - 17.33 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.3 ( 0.77 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eneutrophil count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e19.44 ( 5.25 - 72.02 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.88 ( 2.23 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ewhite blood cell count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e11.66 ( 3.37 - 40.41 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.3 ( 1.71 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003estaphylococcal sepsis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.83 ( 1.77 - 19.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.42 ( 0.89 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"48\" style=\"width: 13px;\"\u003e\n \u003cp\u003e65-85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.39 ( 2.54 - 4.53 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.58 ( 1.17 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003enausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.6 ( 1.91 - 3.55 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.26 ( 0.81 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eplatelet count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1.4 ( 1.02 - 1.91 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.45 ( -0.01 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edifferentiation syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e19.08 ( 12.49 - 29.15 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.37 ( 2.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ediarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1.9 ( 1.33 - 2.73 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.86 ( 0.34 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003easthenia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e1.79 ( 1.21 - 2.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.78 ( 0.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.33 ( 2.2 - 5.05 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.58 ( 0.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edyspnoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.57 ( 1.66 - 3.97 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.25 ( 0.63 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efull blood count decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.04 ( 3.66 - 9.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.28 ( 1.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eblood bilirubin increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.87 ( 3.09 - 11.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.26 ( 1.37 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003einsomnia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e10.53 ( 5.25 - 21.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.87 ( 1.94 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eperipheral swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.14 ( 2.65 - 9.96 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.11 ( 1.19 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ecough\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.48 ( 1.24 - 4.97 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.21 ( 0.25 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ewhite blood cell count increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.2 ( 1.59 - 6.47 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.54 ( 0.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003epain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.15 ( 1.08 - 4.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.02 ( 0.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003erenal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.15 ( 1.08 - 4.27 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.02 ( 0.06 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eheadache\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.59 ( 1.29 - 5.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.27 ( 0.3 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eeastern cooperative oncology group performance status worsened\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e63.08 ( 17.06 - 233.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4.04 ( 2.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003earthralgia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.62 ( 1.26 - 5.48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.28 ( 0.26 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehaemoglobin abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.36 ( 1.59 - 7.09 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.6 ( 0.56 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eweight increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e12.59 ( 4.57 - 34.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e3.04 ( 1.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003esomnolence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.29 ( 2.52 - 15.69 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.34 ( 1.11 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ebone pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e7.49 ( 2.69 - 20.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.53 ( 1.18 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehyperleukocytosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e8.74 ( 3.08 - 24.83 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.69 ( 1.33 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eneutrophil count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.17 ( 2.27 - 16.74 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.32 ( 0.99 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eplatelet count abnormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.56 ( 1.73 - 12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.97 ( 0.67 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eadverse event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.99 ( 2.54 - 19.26 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.45 ( 1.12 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eblood potassium decreased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.81 ( 1.31 - 11.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.75 ( 0.35 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003erash pruritic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.59 ( 1.85 - 16.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.21 ( 0.76 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e2.99 ( 1.05 - 8.54 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.45 ( 0.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehaemoptysis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.35 ( 1.17 - 9.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.6 ( 0.2 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehaematemesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.49 ( 1.03 - 11.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.65 ( 0.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eurticaria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.28 ( 1.73 - 22.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.34 ( 0.7 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003egallbladder disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.71 ( 1.59 - 20.5 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.23 ( 0.61 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edry mouth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e7.86 ( 2.08 - 29.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.58 ( 0.91 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003emouth haemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.83 ( 1.38 - 16.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.04 ( 0.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003echest discomfort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.83 ( 1.38 - 16.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.04 ( 0.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003emuscle spasms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.93 ( 1.14 - 13.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.79 ( 0.21 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eblood pressure increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.7 ( 1.08 - 12.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.72 ( 0.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ejoint swelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.19 ( 1.21 - 14.48 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.87 ( 0.28 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ehypoaesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.83 ( 1.38 - 16.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.04 ( 0.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eblood uric acid increased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.24 ( 1.48 - 18.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.13 ( 0.52 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003etaste disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e5.24 ( 1.48 - 18.58 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.13 ( 0.52 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003egout\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.49 ( 1.03 - 11.86 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.65 ( 0.08 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003earthritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e6.98 ( 1.89 - 25.82 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.45 ( 0.8 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003emyositis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e10.48 ( 2.62 - 41.92 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.87 ( 1.16 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eblood disorder\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.7 ( 1.08 - 12.62 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.72 ( 0.14 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003eswelling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.83 ( 1.38 - 16.98 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.04 ( 0.43 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 13px;\"\u003e\n \u003cp\u003e\u0026gt;85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003efatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.11 ( 1.27 - 7.6 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.42 ( 0.22 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003ediarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e3.94 ( 1.46 - 10.64 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.71 ( 0.38 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003enausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e4.11 ( 1.35 - 12.49 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e1.77 ( 0.31 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31px;\"\u003e\n \u003cp\u003edecreased appetite\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26px;\"\u003e\n \u003cp\u003e9.44 ( 2.72 - 32.72 )\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2.63 ( 1.07 )\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eWe also compared the occurrence of PTs in different age groups, as shown in Figure 2d. As shown in Table 6 The median time to the four age groups was 115 days (IQR 115-115 days), 40 days (IQR 13-109.5 days),43 days (IQR 17-124 days), and 48 days (IQR 28-93 days), respectively. And 0-30 days after medication of 18-64.9, 65-85, and \u0026gt; 85 accounted for 42.3%, 38.7%, and 31.8%, respectively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 6. Onset of PTs induced by enasidenib in different age groups.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003eGroup(years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003e18-64.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 27px;\"\u003e\n \u003cp\u003e65-85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 25px;\"\u003e\n \u003cp\u003e\u0026gt;85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003edays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003epercentage%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003epercentage%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003ecase number\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003epercentage%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0-30 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e42.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e38.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e31.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e31-60 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e17.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e16.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e22.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e61-90 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e8.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e10.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e22.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e91-120 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e7.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e6.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e4.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e121-150 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e3.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e4.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e151-180 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e4.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e4.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e181-360 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e9.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e8.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e4.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21px;\"\u003e\n \u003cp\u003e\u0026gt;360 days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e6.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13px;\"\u003e\n \u003cp\u003e9.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 12px;\"\u003e\n \u003cp\u003e13.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur study showed a higher rate of AEs reported in men than women, probably because of the increasing population diagnosed with AML in males [29], consequently causing more medication opportunities. However, the median onset of all the AEs between male and female patients was almost indistinctive, primarily about 6 to 7 weeks. What\u0026apos;s more, our study revealed a high ratio of AEs in elderly patients (\u0026gt;65 years old), potentially due to the increased AML incidence with age, especially among individuals over 65 years old [6, 29]. Elderly patients are more likely to have a comorbid illness, decreased tissue/organ tolerance to drugs, and impaired organ function, hinting at more occurrence of AEs [30]. Patients aged 65-85 mined the most number of PTs. Furthermore, the median time of the incidence of AEs among all the age groups was a little bit different, the median time in patients under age 18 was the longest, while the median time in other age groups was similar, almost about 6 to 7 weeks. Medical professionals accounted for 63.4% of AE reporters, with reporting almost concentrated in the United States and France. Besides, the number of reported AEs gradually increased from 2017 to 2020, then fell from 2020 to 2024. The use of enasidenib may lead to serious AEs, with approximately 54.8% of reported cases resulting in hospitalization, death, life-threatening, and disability. Our results revealed that enasidenib produces a high incidence of death, so close attention should be paid to AEs, especially serious AEs.\u003c/p\u003e\n\u003cp\u003eIn this study, 78 PTs involving 17 SOCs were identified to be related to enasidenib-induced AEs. High-frequency SOCs were basically detected in reactions for instance investigations, gastrointestinal disorders, general disorders and administration site conditions, and nervous system disorders, consistent with the previous findings of enasidenib [25, 31].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInvestigations with high frequency of occurrence include platelet count decreased, full blood cell count decreased, weight decreased, blood bilirubin increased, etc. Thrombocytopenia was reported as one of the most common AEs in clinical trials [32, 33]. Our study showed the median onset of platelet count decreased was about 5 weeks. As serious platelet count decreases mainly causes bleeding, but thrombosis sometimes [34], it is important to monitor the platelet count and the blood coagulation function in the first two months. Although full blood cell count decreased was not mentioned on the drug label, our study observed a high frequency of occurrence, suggesting the necessity of the routine monitoring of blood cell count. However, weight decrease was mentioned as a symptom related to gastrointestinal disorders in the description. Weight change fast in a short time may reflect the efficiency of the treatment [35], indicating the importance of weight monitoring during medication. Enasidenib may interfere with bilirubin metabolism [36], thus patients would experience elevated liver enzymes or hyperbilirubinemia. Despite the few patients need dose reduction for hyperbilirubinemia, it is still essential to periodically monitor liver enzymes and bilirubin as hyperbilirubinemia generally decreases in frequency with enasidenib treatment continued, but persistent bilirubin elevation may lead to treatment termination [36]. Besides, SOC in investigations and blood and lymphatic system disorders, mined PTs similar to leukocytosis such as white blood cell count increased and hyperleukocytosis. Noninfectious leukocytosis is a risk factor for dosage modifications during medications of enasidenib. It may be related to rapid myeloid proliferation, manifested by leukocytosis [37], usually, there are no clinical signs of infection or differentiation syndrome (DS) concurrently exist. If the patient taking enasidenib was diagnosed with noninfectious leukocytosis, initiating hydroxyurea can improve [38].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is a high frequency of occurrence in gastrointestinal disorders related to enasidenib, such as nausea, diarrhoea, and constipation, consistent with the drug label and clinical trials [39-41]. Females may pay attention to constipation, and males take notice of vomiting. According to the subgroup analysis, it is interesting to know that nausea occurs earlier than diarrhoea, as the median onset of nausea is about 3 weeks and diarrhoea is about 6 weeks. The general disorders and administration site conditions with a high frequency of occurrence include fatigue, asthenia, and peripheral swelling. However, fatigue was commonly reported in clinical trials [17] instead of the instruction manual. The median onset of fatigue was a little long, about 2 months after medication. Peripheral swelling with weight rapid gained may be associated with DS, thus close attention should be paid during medication.\u003c/p\u003e\n\u003cp\u003eWe observed a significant increase in the signal intensity of AEs related to nervous system disorders including dizziness, headache, taste disorder, and somnolence, these AEs are not explicitly mentioned in the manual except for dysgeusia. Dizziness, headache, and taste disorder are the top 20 PTs of enasidenib. To our knowledge, dizziness and somnolence have not been reported in any research yet. This suggests clinicians paying attention to the AEs in nervous system is necessary. It is worth noting that enasidenib is linked to musculoskeletal and connective tissue disorders, which include arthralgia, bone pain, pain in extremity, and joint swelling. However, these AEs are not explicitly mentioned in the manual but in a retrospective study [42], bone pain/arthralgia were reported as signs and symptoms of DS. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor PTs detected in respiratory, thoracic and mediastinal disorders such as dyspnoea and cough are significantly high. Dyspnoea is one of the signs and symptoms of DS, it also has a higher frequency of occurrence, so more attention is needed to early diagnosis and management. Metabolism and nutrition disorders are frequent AEs of enasidenib, and include decreased appetite which has been noted on the drug label, is one of the most common and serious AEs for reducing patients\u0026rsquo; medication compliance. Decreased appetite may reduce nutrition and energy intake, while the reduction in energy intake may lead to subclinical deficits that directly affect the immunity function in the elderly [43]. The median onset of decreased appetite is about 4 weeks, quite close to the median onset of DS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDS has a high frequency of occurrence in malignant and unspecified. It is primarily reported in clinical studies and instruction manuals [3, 24, 25, 31, 36]. It is of course a common and potentially fatal AEs of enasidenib that is listed as a boxed warning in the package insert. DS may often result in discontinuation or dose reduction of the medications in patients [44, 45]. The occurrence identified with DS was 1.92%, ranking 6\u003csup\u003eth\u003c/sup\u003e. DS occurs as early as 1 day and up to 3-5 months after administration, the median time to onset is 10-30 days [23, 38, 42, 46], as reported. Our results showed that the median onset of DS is 24 days. Therefore, special attention should be paid if the patient develops symptoms such as fever, dyspnea, peripheral edema with rapid weight gain, decreased appetite, especially in the first month of taking enasidenib, as they may induce severe AEs, even death. As a response to DS, corticosteroid therapy needs to be initiated and hemodynamic monitoring [45].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnexpected and significant safety SOCs, such as surgical and medical procedures, psychiatric disorders, injury, poisoning and procedural complications, skin and subcutaneous tissue disorders, immune system disorders, infections and infestations, were mined in our study. PTs in surgical and medical procedures were mined significantly related to enasidenib such as hospitalization. As previously mentioned, enasidenib may induce a relatively high rate of hospitalization and death, once patients develop dyspnoea or symptoms of DS, early professional medication is urgent and helpful.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePTs in psychiatric disorders including insomnia, anxiety, and depression were identified, suggesting that clinicians and family members should pay attention to the mental state of the patients during medications. Our study also observed PTs in injury, poisoning and procedural complications, mainly including falls, this AE is also an unexpected adverse reaction of enasidenib. It is reported that 33% of older adults fall every year [47, 48]. The incidence of falls may associated with the use of drugs, primarily because of side effects such as dizziness, balance disorders or asthenia, etc. [49]. In all, if a patient develops AEs such as dizziness or asthenia during the medication, it is necessary to remind the risk of falls.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIt is a concern about skin and subcutaneous tissue disorders, such as pruritus and acute febrile neutrophilic dermatosis, although the number of PTs is not so big, are not explicitly mentioned in the manual. The mechanism of pruritus secondary to enasidenib is still unknown. Parisi R et. al [50], found that pruritus was a common dermatologic adverse event(DAE), and the median onset was 53 days. Even if associated DAE do not increase mortality, they could reduce the quality of life and the tolerance of treatment in patients with AML. Thus, early identification and symptomatic management of DAE are very necessary, especially during the first 2 months of initiations. Acute febrile neutrophilic dermatosis, usually concurrently with neutrophilic inflammatory infiltrate may be similar to the symptoms of infections [1,51].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, a few PTs in immune system disorders and infections and infestations were detected, including seasonal allergy, nasopharyngitis, and coronavirus infection. However, these AEs are not explicitly mentioned in the manual. Similar situations are also shown in renal and urinary disorders, such as renal disorder, pollakiuria, nephrolithiasis, and chromaturia. So it is also important to monitor the function of the kidney during medications. To improve the prognosis of the above-mentioned AEs, early diagnosis, proper treatment, and prevention are important and necessary.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeanwhile, we found different PTs among males and females, as shown in Figure 2. No matter what the gender is the patient, AEs like\u0026nbsp;nausea, fatigue, decreased appetite, diarrhoea, etc, may occur during the\u0026nbsp;initiation\u0026nbsp;of\u0026nbsp;enasidenib.\u0026nbsp;Males are more likely to experience AEs such as vomiting, falls, and cough while AEs like\u0026nbsp;constipation, peripheral swelling, and bone pain occur more often in\u0026nbsp;females. Based on this, clinicians could take different management and drug education according to gender.\u003c/p\u003e\n\u003cp\u003eThe number of AEs increased gradually as the age increased to 85, and patients aged 65-85 mined the most number of AEs. This is consistent with the occurrence of AML, as the number of patients diagnosed with AML is increasing with age, especially at age 65 and above [8]. Since the use of enasidenib in groups of children is an off-label use, the safety among this population is uncertain. Due to the fact that older patients aged 60 and above were more often developing multiple comorbidities [52], it is needed to be more cautious. As the results shown in Table 5, populations aged 18-64.9 were more commonly to take place AEs such as pyrexia, sepsis, and colitis, while AEs like platelet count decreased, diarrhoea, and peripheral swelling, primarily occurred more often in patients aged 65-85. However, AEs for instance DS, nausea, fatigue, asthenia, decreased appetite, dyspnoea, full blood count decreased, and blood bilirubin increased, were both commonly detected among populations aged 18-85.\u003c/p\u003e\n\u003cp\u003eThe median time for detecting AEs with enasidenib was 47 days (IQR 18-118 days), and more than 54% of AEs occurred within 60 days. The median onset of nausea, decreased appetite and DS were within the first month, while platelet count decreased and diarrhoea were 5-7 weeks after medication. According to these results, it is recommended that longer follow-up periods will be required in future clinical studies to monitor AEs.\u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study analyzed AEs signals associated with enasidenib based on the FAERS to enhance clinical medication safety. The AEs identified in this study largely align with those documented in the enasidenib\u0026apos;s manual. Additionally, we uncovered AEs not previously listed, including fatigue, asthenia, platelet count decreased, full blood count decreased, dizziness, constipation, etc. These findings supplement the limited sample size of pre-market clinical studies of enasidenib. Gender-specific and age-specific patients should be concerned about the occurrence of appropriate AEs. However, the FAERS is a spontaneous reporting system with significant reporting bias (selective and underreporting) and has missing data. And we have not yet explored the correlation between AEs and the drug itself, underscoring the need to augment safety information. Further research is still warranted to elucidate the relationship between AEs and enasidenib. \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval\u003c/p\u003e\n\u003cp\u003eSince FEARs is a public database, this study does not require ethics committee approval.\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003eConflict and interest\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003eData availability statement:\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article or Supplementary Materials, further inquiries can be directed to the corresponding author.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eAll named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, J.X., Q.G., and Y.C. designed the research; J.X., Q.G., performed the analyses; J.X. and L.X., and Y.Q. collected and interpreted data; J.X. and Q.G. wrote the paper; J.X., QG., L.X., Y.Q., and Y.C. critically revised the paper; L.X. and Y.C. final approved of the version to be published. All authors contributed to the article and approved the submitted version.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAyyash, A. M. \u0026amp; Sampath, R. Acute Febrile Neutrophilic Dermatosis. \u003cem\u003eNEW. ENGL. J. MED.\u003c/em\u003e \u003cb\u003e385\u003c/b\u003e, e14 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBray, F. et al. Global Cancer Statistics 2022: Globocan Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. \u003cem\u003eCA-CANCER J. CLIN.\u003c/em\u003e \u003cb\u003e74\u003c/b\u003e, 229\u0026ndash;263 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCai, S. F. et al. 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HEALTH\u003c/em\u003e. \u003cb\u003e5\u003c/b\u003e, e16\u0026ndash;e27 (2023).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"FAERS, enasidenib, isocitrate dehydrogenase inhibitor, adverse events, acute myelogenous leukemia","lastPublishedDoi":"10.21203/rs.3.rs-6698707/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6698707/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEnasidenib, an isocitrate dehydrogenase inhibitor (IDHI) that selectively inhibits IDHI-2, is currently approved for treating Acute Myelogenous Leukemia(AML). This study identified and characterized adverse events (AEs) significantly related to IDHI in treating AML and compared the differences of subgroups to provide clinical reference. AEs reports were collected from the United States Food and Drug Administration Adverse Event Reporting System(FAERS). Enasidenib\u0026rsquo;s AEs were collected from Q3 2017 to Q3 2024. The reporting odds ratio (ROR) and Bayesian confidence propagation neural network(BCPNN) were used. When the lower limit of the 95% confidence interval (CI) of ROR\u0026thinsp;\u0026gt;\u0026thinsp;1.0 and (IC-2SD)\u0026gt;0 was considered the threshold for a signal. A total of 2098 AE reports were retrieved from FAERS. Reports for males were higher than females, and patients aged 65\u0026ndash;85 years reported the highest number of AEs. Interestingly, 52 PTs were classified as unexpected AEs, such as fatigue, asthenia, platelet count decreased, etc. There are similarities and differences in the presentation of enasidenib-related AEs in subgroups of different genders and ages. Gender-specific and age-specific patients should be concerned about the occurrence of appropriate AEs when taking enasidenib. Our study provided evidence for enasidenib in the treatment of AML.\u003c/p\u003e","manuscriptTitle":"Risk factors and subgroups analysis of Enasidenib in treating Acute Myelogenous Leukemia : a pharmacovigilance study based on FAERS database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-21 10:19:11","doi":"10.21203/rs.3.rs-6698707/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e36f085f-87ac-42ea-a1c0-d7397439e39f","owner":[],"postedDate":"August 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53196066,"name":"Biological sciences/Cancer"},{"id":53196067,"name":"Biological sciences/Drug discovery"},{"id":53196068,"name":"Biological sciences/Immunology"},{"id":53196069,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-04-22T11:10:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-21 10:19:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6698707","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6698707","identity":"rs-6698707","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}