Evaluating the Real-World Safety Profile of Etrasimod in the Treatment of Ulcerative Colitis: A Comprehensive Analysis from FAERS Database

Evaluating the Real-World Safety Profile of Etrasimod in the Treatment of Ulcerative Colitis: A Comprehensive Analysis from 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 Evaluating the Real-World Safety Profile of Etrasimod in the Treatment of Ulcerative Colitis: A Comprehensive Analysis from FAERS Database Qian Guo, Meirong Shan, Wei Gao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6187859/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 21 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Etrasimod is a sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5, but exhibits no detectable activity on S1P2 and S1P3. It is primarily used for the treatment of ulcerative colitis (UC). There has been limited research on the adverse events (AEs) associated with etrasimod during its use in treating UC, necessitating a comprehensive and real-world evaluation of its clinical safety. This study aims to assess the AEs of etrasimod in UC patients using data from the FDA Adverse Event Reporting System (FAERS) database. By analyzing all AEs in the FAERS database since 2004, the safety of etrasimod in clinical applications was evaluated. Based on the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinkage (MGPS), we employed disproportionality analysis to identify all adverse event reports associated with etrasimod in clinical application. Additionally, this study utilized standardized MedDRA queries to identify AEs related to etrasimod. Our research provides real-world evidence on the safety profile of etrasimod, which is crucial for clinicians to safeguard patient health. Biological sciences/Drug discovery/Drug safety Health sciences/Diseases Etrasimod Ulcerative colitis FAERS Disproportionality analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction Ulcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colonic mucosa, starting in the rectum and typically extending proximally in a continuous manner, involving part or the entire colon 1 . UC is characterized by rectal bleeding, diarrhea, urgency, and tenesmus and these symptoms are associated with a diminished quality of life 2 . The goal of UC treatment is to achieve and maintain long-term clinical and endoscopic remission 3 . It is caused by a combination of genetic predisposition and environmental factors, leading to alterations in the gut microbiota and interactions with the immune system 4 . UC is characterized by alternating periods of active inflammation and remission. By 2023, the global prevalence of UC is estimated to be 5 million cases annually 4 . Patients with UC report a reduced quality of life due to symptoms such as diarrhea and rectal haemorrhage, as well as increased rates of depression, anxiety, sleep disturbances, and sexual dysfunction. The risk of developing colorectal cancer in UC patients 20 years after diagnosis is 4.5%, which is 1.7 times higher than that of the general population 5 . The goals of UC treatment include achieving long-term, sustained clinical and endoscopic remission, and avoiding surgical resection of the affected colon 6 . Sphingosine 1-phosphate (S1P) and its receptors (S1PRs) are involved in the pathogenesis of various immune-mediated inflammatory diseases. S1P regulates the trafficking of T cells and B cells, and its binding to the S1P1 receptor reversibly sequesters specific lymphocyte subsets within lymph nodes, leading to a reduction in peripheral immune cells and contributing to immune-related diseases such as UC 7 ; 8 . Therefore, S1PR modulators offer a novel therapeutic option for UC patients. Etrasimod is a novel, small-molecule, oral S1PR1 receptor modulator, currently under clinical development for the treatment of immune-mediated inflammatory diseases, including UC 9 . Dose-dependent relationships between etrasimod plasma concentrations and lymphocyte counts have been observed in mice, and long-term use of the drug has been found to reduce inflammation in mouse models of colitis 9 . Additionally, research has found that analysis of lymphocyte subsets indicates etrasimod can reduce pro-inflammatory immune cells and functions as a selective immunomodulator rather than a broad-spectrum immunosuppressant 10 . This drug was first approved in the United States in October 2023 for the treatment of adults with moderate to severe active UC 11 . In several Phase II and III randomized, double-blind, placebo-controlled trials targeting adult patients with moderate to severe active UC, the oral dose of 2mg etrasimod demonstrated greater efficacy than placebo in clinical and endoscopic improvements and was generally well-tolerated 12 – 14 . Furthermore, the short-term safety of etrasimod was confirmed in these Phase II and III clinical trials. In a long-term open-label extension (OLE) study, adult patients with moderate to severe active UC who took 2mg of etrasimod once daily for 52 weeks showed good tolerance, with no treatment-related serious infections or new safety signals observed 6 . The OLE study provided support for the long-term safety and sustained clinical efficacy of etrasimod in treating adult patients with moderate to severe active UC. The FDA Adverse Event Reporting System (FAERS) is a database maintained by the FDA to collect and analyze post-marketing safety data on drugs and therapeutic biologics 15 . This database is used to monitor the safety of marketed drugs and biologics, identify potential AEs, and support FDA regulatory decisions 16 . AEs and medication error reports in the database are voluntarily submitted by healthcare professionals (such as doctors, pharmacists, nurses, etc.) and consumers 17 . For over a decade, FAERS has been widely used to identify drug AEs, such as 22 drugs significantly associated with the risk of autoimmune hepatitis 16 and neurological adverse events associated with blinatumumab 18 . The aim of this study is to describe etrasimod-related AEs by extracting relevant data from FAERS using various analytical methods. By evaluating the real-world safety of etrasimod, it can provide guidance for clinicians on safe medication use. In conclusion, etrasimod provides a new treatment option for moderate to severe UC. However, a detailed evaluation of its safe use is necessary. This study aims to provide evidence for clinical safety by investigating post-marketing adverse drug events (ADEs) of etrasimod using the FAERS database. Results Annual and quarterly distribution of etrasimod AE reports From September 2023 to December 2024, the FDA received a total of 1,406 AE reports related to etrasimod as the PS. Statistical results indicate that the number of AE reports increased quarter by quarter, with the specific distribution shown in Fig. 1 . Descriptive analysis This study collected 663 AE reports from the FAERS database between 2004 and 2024, in which etrasimod was identified as the PS for the AEs. We drilled down further analysis on these data to explore the drug's safety profile. Among the reports, females accounted for 44.65%, while males accounted for 42.23%. The distribution varied by age, with the largest proportion being 18–44 years old (36.8%), followed by 45–64 years old (30.02%). The majority of AE reports were submitted in 2024, attaining 98.64%. Consumers were the primary reporters, representing 43.29% of the reports. The reports mainly originated from the United States (95.17%), followed by Canada (2.87%). Excluding cases with unknown severity, the most common serious AE was hospitalization (4.68%), followed by death (0.3%). In terms of the temporal distribution of adverse reactions, excluding cases with uncertain onset times, the highest incidence of adverse reactions occurred within 30 days (3.92%). Further descriptive results are provided in Table 1 . Table 1 Clinical characteristics of adverse event reports related to etrasimod from the FAERS database (Q4 2023–Q4 2024). Characteristics Number of cases Proportion of cases (%) Number of events 663 Sex Female 296 44.65 Male 280 42.23 Missing 87 13.12 Age <18 2 0.30 18–44 244 36.80 45–64 199 30.02 ≥ 65 75 11.31 Missing 143 21.57 Reporting year 2023 9 1.36 2024 654 98.64 Top 4 reporting countries America 631 95.17 Canada 19 2.87 Puerto Rico 4 0.60 Australia 3 0.45 Reporter Consumer 287 43.29 Pharmacist 155 23.38 Physician 221 33.33 Severe outcomes in etrasimod Among the 1,406 AE reports related to etrasimod, there were a total of 560 serious outcomes, including hospitalization (4.68%), disability (0.3%), and other outcomes (34.84%). Details are shown in the Fig. 2 . Distribution of AEs at the SOC level AE reports related to etrasimod were documented in 24 out of 27 SOC categories. The distribution of these AEs is illustrated in Fig. 3 . Significant findings included general disorders and administration site conditions, gastrointestinal diseases, eye disorders, nervous system diseases, infections and infestations, skin and subcutaneous tissue disorders, musculoskeletal and connective tissue disorders, mental disorders, immune system disorders, circulatory and respiratory system disorders, blood and lymphatic system disorders, liver and bile system disorders, etc. Although the drug affects a wide range of organ systems, many SOC categories were found to have no statistically significant association with etrasimod (as illustrated in Table 2 ). Table 2 Signal strength of etrasimod related adverse events across system organ classes (SOCs) in the FDA Adverse Event Reporting System database. SOCs Number of cases ROR (95% CI) PRR (χ2) EBGM (EBGM05) IC (IC025) General disorders and administration site conditions* 354 1.59(1.41,1.80) 1.44(58.45) 1.44(1.28) 0.53(0.36) Gastrointestinal disorders* 253 2.36(2.06,2.71) 2.12(162.99) 2.12(1.85) 1.08(0.88) Eye disorders* 134 5.18(4.34,6.19) 4.78(408.85) 4.78(4.00) 2.26(1.96) Nervous system disorders 119 1.00(0.83,1.20) 1.00(0.00) 1.00(0.83) 0.00(-0.28) Metabolism and nutrition disorders* 101 3.49(2.85,4.28) 3.31(166.73) 3.31(2.71) 1.73(1.40) Investigations 95 1.11(0.90,1.36) 1.10(0.94) 1.10(0.89) 0.14(-0.17) Infections and infestations 56 0.75(0.57,0.98) 0.76(4.54) 0.76(0.58) -0.40(-0.78) Skin and subcutaneous tissue disorders 47 0.61(0.45,0.81) 0.62(11.59) 0.62(0.46) -0.69(-1.10) Injury, poisoning and procedural complications 40 0.25(0.18,0.35) 0.27(86.15) 0.27(0.20) -1.87(-2.30) Musculoskeletal and connective tissue disorders 39 0.52(0.38,0.72) 0.54(16.49) 0.54(0.39) -0.90(-1.35) Psychiatric disorders 26 0.32(0.21,0.47) 0.33(37.76) 0.33(0.22) -1.60(-2.13) Immune system disorders* 24 1.56(1.04,2.33) 1.55(4.71) 1.55(1.03) 0.63(0.02) Cardiac disorders 23 0.62(0.41,0.93) 0.62(5.39) 0.62(0.41) -0.68(-1.26) Respiratory, thoracic and mediastinal disorders 21 0.31(0.20,0.47) 0.32(32.36) 0.32(0.21) -1.66(-2.23) Vascular disorders 21 0.70(0.45,1.07) 0.70(2.74) 0.70(0.46) -0.51(-1.11) Renal and urinary disorders 12 0.44(0.25,0.78) 0.45(8.29) 0.45(0.25) -1.16(-1.90) Blood and lymphatic system disorders 8 0.33(0.17,0.67) 0.34(10.61) 0.34(0.17) -1.57(-2.42) Hepatobiliary disorders 7 0.54(0.26,1.14) 0.54(2.73) 0.54(0.26) -0.88(-1.82) Surgical and medical procedures 6 0.31(0.14,0.70) 0.32(9.01) 0.32(0.14) -1.66(-2.61) Ear and labyrinth disorders 5 0.82(0.34,1.97) 0.82(0.20) 0.82(0.34) -0.29(-1.42) Neoplasms benign, malignant and unspecified (incl cysts and polyps) 5 0.13(0.06,0.32) 0.14(28.26) 0.14(0.06) -2.88(-3.84) Endocrine disorders 5 1.40(0.58,3.36) 1.40(0.56) 1.40(0.58) 0.48(-0.79) Reproductive system and breast disorders 4 0.32(0.12,0.85) 0.32(5.81) 0.32(0.12) -1.64(-2.72) Social circumstances 1 0.15(0.02,1.08) 0.15(4.72) 0.15(0.02) -2.71(-3.96) Asterisks (*) indicate statistically significant signals. Abbreviations: ROR, reporting odds ratio; PRR, proportional reporting ratio; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of the 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of the 95% confidence interval of the IC. Distribution of AEs at the PT level Analysis of AEs at the PT level included ranking etrasimod-related AEs by frequency and evaluating positive signals. Figure 4 displays the 50 most common adverse reactions and known adverse reactions, which include hypertension, bradycardia, dyspnea, and macular edema. Moreover, potential adverse reactions not listed on the label were identified, such as type 2 diabetes mellitus (T2DM), diabetic eye disease, headache, dizziness, fatigue, malaise, diarrhea, nausea, UC, hematochezia, rash, and others. Details of these findings are exhibited in Table 3 . Comprehensive information on all AEs meeting the positive signal criteria can be found in Supplementary Table S1 . Table 3 Top 50 most frequent adverse events for etrasimod at the preferred term (PT) level. PT Case Numbers ROR (95% CI) PRR (χ2) EBGM (EBGM05) IC (IC025) Drug ineffective* 110 3.91(3.22,4.75) 3.68(219.44) 3.68(3.03) 1.88(1.56) Type 2 diabetes mellitus* 81 108.17(86.41,135.41) 101.99(8084.03) 101.73(81.27) 6.67(5.18) Diabetic eye disease* 65 7232.24(5526.88,9463.81) 6897.94(381415) 5869.72(4485.64) 12.52(5.64) Condition aggravated* 46 7.27(5.42,9.75) 7.07(240.61) 7.06(5.27) 2.82(2.22) Headache* 43 3.07(2.26,4.16) 3.00(58.10) 3.00(2.22) 1.59(1.08) Dizziness* 32 2.86(2.01,4.06) 2.81(37.75) 2.81(1.98) 1.49(0.91) Fatigue* 30 1.73(1.20,2.48) 1.71(8.97) 1.71(1.19) 0.77(0.22) Diarrhoea* 26 1.82(1.24,2.69) 1.81(9.49) 1.81(1.23) 0.85(0.25) Malaise* 26 2.58(1.75,3.80) 2.55(24.69) 2.55(1.73) 1.35(0.71) Colitis ulcerative* 23 25.01(16.56,37.77) 24.62(521.18) 24.60(16.29) 4.62(3.04) Nausea 23 1.29(0.86,1.95) 1.29(1.49) 1.29(0.85) 0.36(-0.25) Off label use 22 1.20(0.79,1.83) 1.19(0.71) 1.19(0.78) 0.26(-0.36) Drug interaction* 21 5.86(3.81,9.02) 5.79(83.42) 5.79(3.76) 2.53(1.63) Haematochezia* 21 17.34(11.27,26.69) 17.10(318.47) 17.09(11.11) 4.10(2.68) Rectal haemorrhage* 16 16.24(9.92,26.58) 16.06(226.06) 16.06(9.81) 4.01(2.39) Pain 15 1.06(0.64,1.76) 1.06(0.05) 1.06(0.64) 0.08(-0.65) Therapeutic product effect incomplete* 15 6.23(3.74,10.36) 6.17(65.08) 6.17(3.71) 2.63(1.49) Colitis* 14 17.03(10.06,28.84) 16.87(209.07) 16.87(9.96) 4.08(2.29) Vision blurred* 14 4.57(2.70,7.74) 4.54(38.68) 4.54(2.68) 2.18(1.13) Rash 13 1.27(0.74,2.20) 1.27(0.76) 1.27(0.74) 0.35(-0.46) Nasopharyngitis* 12 2.93(1.66,5.17) 2.91(15.11) 2.91(1.65) 1.54(0.54) Hypersensitivity* 11 2.64(1.46,4.78) 2.63(11.11) 2.63(1.45) 1.39(0.37) Pyrexia 11 1.39(0.77,2.52) 1.39(1.20) 1.39(0.77) 0.47(-0.41) Diabetic retinopathy* 10 129.62(69.52,241.69) 128.71(1263.08) 128.29(68.80) 7.00(2.48) Heart rate decreased* 10 12.27(6.58,22.85) 12.19(102.70) 12.18(6.54) 3.61(1.72) Arthralgia 9 0.97(0.50,1.87) 0.97(0.01) 0.97(0.50) -0.04(-0.95) Bradycardia* 9 7.28(3.78,14.03) 7.24(48.48) 7.24(3.76) 2.86(1.24) Gastrointestinal disorder* 9 3.34(1.74,6.44) 3.33(14.67) 3.33(1.73) 1.73(0.52) Abdominal pain 8 1.52(0.76,3.05) 1.52(1.43) 1.52(0.76) 0.60(-0.44) Abdominal pain upper 8 1.74(0.87,3.48) 1.73(2.49) 1.73(0.86) 0.79(-0.29) Alopecia 8 1.79(0.89,3.58) 1.78(2.75) 1.78(0.89) 0.83(-0.25) Asthenia 8 0.93(0.46,1.86) 0.93(0.04) 0.93(0.46) -0.10(-1.06) Constipation 8 1.68(0.84,3.38) 1.68(2.21) 1.68(0.84) 0.75(-0.32) Drug hypersensitivity 8 1.79(0.89,3.58) 1.78(2.75) 1.78(0.89) 0.83(-0.25) Dyspnoea 8 0.62(0.31,1.24) 0.62(1.88) 0.62(0.31) -0.69(-1.59) Frequent bowel movements* 8 13.88(6.93,27.81) 13.80(95.02) 13.80(6.89) 3.79(1.54) Hypertension 8 1.66(0.83,3.33) 1.66(2.11) 1.66(0.83) 0.73(-0.34) Inflammation* 8 7.13(3.56,14.29) 7.10(41.94) 7.10(3.54) 2.83(1.12) Illness* 8 4.27(2.13,8.57) 4.26(19.95) 4.26(2.12) 2.09(0.68) Macular oedema* 7 56.20(26.73,118.17) 55.93(377.10) 55.85(26.56) 5.80(1.81) Defaecation urgency* 6 41.04(18.40,91.55) 40.87(233.15) 40.83(18.30) 5.35(1.52) Dyspepsia* 6 2.74(1.23,6.10) 2.73(6.59) 2.73(1.22) 1.45(0.04) Feeling abnormal 6 1.06(0.48,2.37) 1.06(0.02) 1.06(0.48) 0.09(-1.02) Hypoaesthesia 6 1.73(0.77,3.85) 1.72(1.83) 1.72(0.77) 0.79(-0.45) Inflammatory bowel disease* 6 26.41(11.84,58.89) 26.30(145.94) 26.28(11.78) 4.72(1.42) Pruritus 6 0.70(0.31,1.56) 0.70(0.78) 0.70(0.31) -0.52(-1.55) Visual impairment 6 2.09(0.94,4.66) 2.08(3.39) 2.08(0.93) 1.06(-0.24) Vomiting 6 0.57(0.25,1.26) 0.57(1.98) 0.57(0.26) -0.81(-1.82) Blood cholesterol abnormal* 5 47.33(19.66,113.94) 47.16(225.67) 47.11(19.57) 5.56(1.26) Blood pressure abnormal* 5 11.44(4.75,27.53) 11.40(47.45) 11.40(4.74) 3.51(0.88) Asterisks (*) indicate statistically significant signals. Abbreviations: ROR, reporting odds ratio; PRR, proportional reporting ratio; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of the 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of the 95% confidence interval of the IC. Subgroup analysis of etrasimod-related AEs Subgroup analysis revealed that among the 50 most common AEs meeting the positive signal criteria, no gender-specific AEs were identified. However, adverse events related to hepatobiliary dysfunction (elevated liver enzymes, hepatic cysts, cholangitis, cholecystitis, cholelithiasis, hepatocellular injury, and hepatitis) were found exclusively in males. Detailed data are provided in Supplementary Tables S2 and S3. Only two adverse event reports involved patients under the age of 18, including colitis and lymphocyte count decreased. Among patients aged 18–44, the 50 most common positive AEs included T2DM, haematochezia, UC, diarrhea, nausea, diabetic retinopathy, rectal haemorrhage, hypersensitivity, and abdominal pain. In the 45–64 age group, AEs mainly contained T2DM, nausea, diarrhea, UC, rectal haemorrhage, hypersensitivity, constipation, haematochezia, rash, hypertension, and diabetic retinopathy. For patients ≥ 65, common AEs covered diarrhea, rash, rectal haemorrhage, colitis, nausea, hypersensitivity, and haematochezia. (Detailed information can be found in Supplementary Tables S4-S7). Analysis of the onset time and weibull distribution of etrasimod AEs Analysis of onset time of AEs during treatment with etrasimod showed that most AEs occurred within the first 30 days of treatment, except for reports of unknown onset time (Fig. 5 ). The cumulative incidence curve of AEs is displayed in Fig. 6 . The weibull distribution analysis indicated the early failure mode, and the results showed that the median time to onset (TTO) of AEs was 41 days (IQR: 0–43 days). The scale parameters (α) and shape parameters (β) are 44.13 (95% CI: 26.67–73.03) and 0.75 (95% CI: 0.57–0.99), respectively. Detailed parameters are shown in Table 4 . Table 4 Analysis of time to onset of etrasimod-related adverse events and Weibull distribution. Drug Time to onset (days) Weibull distribution Case reports Median (IQR) Scale parameter: α (95% CI) Shape parameter: β (95%CI) Type Etrasimod 41 41(0–43) 44.13 (95% CI: 26.67–73.03) 0.75 (95% CI: 0.57–0.99) Early failure Discussion Using real-world data from the FAERS database, this study comprehensively evaluated the AEs following the marketing of etrasimod in 2023. The study confirmed adverse reactions already identified on the label such as hypertension, bradycardia, dyspnea, and macular edema. In addition, unlabeled adverse events were found including T2DM, diabetic eye disease, gastrointestinal disorders (diarrhea, nausea, UC, hematochezia), neurological disorders (headache, dizziness), fatigue, rash, hypersensitivity reactions, etc. These findings suggest the necessity of drug safety monitoring and provide clinicians with more comprehensive risk management information. Among 527 patients treated with etrasimod in the ELEVATE UC 52 and ELEVATE UC 12 trials, a total of 9 bradycardia events (1.7%) and 3 asymptomatic atrioventricular block events (0.6%) were reported 13 . In the placebo-controlled UC cohort, the proportion of hypertension-associated treatment-emergent adverse events (TEAEs) and IR were numerically higher in patients receiving etrasimod (n = 15 (2.6%) IR 5.31 (95% CI 2.62–7.99) vs placebo (n = 4 (1.3%) IR 3.40 (95% CI 0.07 to 6.72) 19 . And 14 patients (2.4%) receiving etrasimol were assessed as hypertensive AE of special interest (AESI) 19 . In the placebo-controlled UC cohort, two patients developed macular edema (0.3%; IR: 0.70) 20 . The AEs on the label are consistent with our findings. Our study also revealed AEs that are not currently listed on the drug label, with the most common AEs in etrasimod's Phase III clinical trial being headache and dizziness, with an incidence of ≥ 5%. Additionally in the open-label extension (OLE) of OASIS study, 60% of patients treated with etrasimod 2mg experienced AEs(67/112), and 94.4% of the AEs were mild or moderate severity 6 . In the OLE the most common TEAEs are the worsening UC and anemia and their percentages were 19% and 11%, respectively 6 . Furthermore, in ELEVATE UC 52 and ELEVATE UC UC 12 study, among all isolated proctitis patients, the most common TEAEs in ≥ 4% of patients receiving etrasimod included headaches, arthralgia, and increased blood creatine phosphokinase 21 . However, among patients with more extensive colitis, the most common TEAEs were headache, worsening UC and pyrexia 21 . Patients with isolated proctitis had no liver damage, pulmonary disease, malignancy, or macular edema, whereas patients with more extensive colitis treated with etrasimod suffered from these AEs 21 . Therefore, these unlisted AEs should be closely monitored, and clinicians should carefully evaluate the situation of patients to determine the administration time; avoid adverse reactions caused by too long medication time, and try to achieve the best therapeutic effect within the full course of treatment. Otherwise regular review of colonoscopy, electrocardiogram, blood routine, liver function, etc., can detect some AEs earlier, and timely adjust the treatment to avoid serious AEs. Patients with UC have a high prevalence of mental disorders such as depression and anxiety 22 . A multi-center study from China showed that the proportion of mental disorders in IBD patients was 7.69%, among which UC patients had a higher prevalence of anxiety and depression compared with CD patients 23 . The treatment of UC by etrasimod may result in worsening UC, which may lead to or aggravate mental disorders. In addition, In addition, attention should be paid to other adverse reactions caused by etrasimod, such as dizziness and headache. Such non-fatal AEs will affect the treatment compliance and adversely affect the therapeutic effect. Therefore, effective treatment of UC can significantly improve patients' quality of life. In this study, we conducted a temporal analysis of AEs, and predicted the time period of AEs according to Weibull distribution. And their results highlight the importance of monitoring, especially during the first month of etrasimod treatment. Frequent clinical follow-up within the first month is recommended, and early monitoring is essential to detect and prevent potential adverse reactions. Patients are encouraged to report early symptoms of AEs in a timely manner, thereby optimizing patient compliance and safety with the aim of improving overall patient outcomes. The research also found differences in certain SOCs, with no statistically significant signals observed. Reasons for this outcome may be multifaceted. Primarily, it could be attributed to the disproportionality analysis method, which evaluates adverse event reporting rates relative to the entire FAERS database rather than raw frequencies. Moreover, the broad nature of SOCs may dilute overall statistical significance, even if differences exist in specific AEs within a category. In addition, the pharmacological targets of drugs may span multiple system organs, leading to counteracting effects that obscure statistically significant signals. Furthermore, similarities in patients' baseline characteristics and high baseline reporting rates for certain SOCs could also diminish statistical differences. It should be noted that this study has several limitations. First, the FAERS database relies on a voluntary reporting mechanism, which may lead to underreporting or overreporting by those using the system. For example, severe AEs or those with high media attention may be frequently reported, while milder AEs may be overlooked. Second, there are issues of data incompleteness and data entry errors, such as missing critical information in reports (e.g., medical history, drug dosage, severity of symptoms, etc.). Third, although the dataset analyzed in this study includes multiple reports, it remains limited in scope, and a larger dataset is needed to validate our findings. Fourth, reporting heterogeneity also plays a role, as differences in reporting habits among individuals and uneven distribution of medical resources may introduce bias into the data. Finally, disproportionality analysis is used to identify positive signals of AEs, but it has limitations in establishing a causal relationship between etrasimod and AEs. To address these limitations, technical approaches (such as data cleaning and machine learning), integration of multiple data sources, international collaboration, and improvements in reporting mechanisms can be employed. Additionally, combining real-world evidence and epidemiological studies can further enhance the reliability and practicality of the data. Therefore, long-term prospective studies are still needed to confirm the potential adverse reactions identified. In summary, this study utilized the FAERS database to conduct a comprehensive analysis of real-world AEs associated with etrasimod, particularly focusing on reports since 2023. The findings confirmed known adverse reactions listed on the label, while also identifying potential AEs not mentioned on the label, such as T2DM, diabetic eye disease, worsening UC, dizziness, headache, fatigue, diarrhea, nausea, bloody stools, rash, and others. Additionally, subgroup analysis and temporal analysis revealed the populations most susceptible to AEs and the time periods during which these events were most likely to occur. These results provide crucial safety information for clinicians using etrasimod in the future, enabling better optimization of treatment plans and ultimately improving patient outcomes. Methods Data extraction The raw data used in this study were obtained from the FAERS database, which is publicly available on the official website of the U.S. FDA ( https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html ). The database has been accessible since the first quarter of 2004 and is updated and released quarterly. For this study, the raw ASCII data packages were downloaded for data mining and statistical analysis. The search term used was 'etrasimod. The FAERS database consists of seven distinct data files, including demographic and administrative information (DEMO), detailed drug information (DRUG), drug indications (INDI), reported adverse events (REAC), patient outcomes (OUTC), report sources (RPSR), and drug therapy (THER). Records screened Duplicate reports were removed based on the FDA-recommended deduplication method. The PRIMARYID, CASEID, and FDA_DT fields from the DEMO table were selected, and the data were sorted by CASEID, FDA_DT, and PRIMARYID. For reports with the same CASEID, the one with the largest FDA_DT value was retained. If both CASEID and FDA_DT were identical, the report with the largest PRIMARYID value was kept. Data processing In the DEMO data, a total of 22,375,298 AEs related to etrasimod were recorded. After excluding duplicate records (n = 3,761,306), the final number of DEMO records was determined to be 18,613,992. By screening the drug data (n = 66,418,951), we identified reports where etrasimod was considered the primary suspect drug (PS), excluding data related to secondary suspect (SS) and concomitant (C) drugs. Combined with the REAC data (n = 55,357,463), a total of 1406 AEs were ultimately confirmed as primarily associated with etrasimod as the PS. AEs in the FAERS database are reported from Preferred Term (PT), Advanced Group Term (HLGT), Advanced Term (HLT), System Organ Category (SOC), and Lowest Level Term (LLT) according to the Medical Dictionary for Regulatory Activities (MedDRA). The detailed steps for filtering etrasimod-related data from FAERS are shown in Fig. 7 . Statistical analysis Descriptive analysis was applied to depict reports of adverse events associated with etrasimod. Four disproportionation analyses were employed to examine the association of etrasimod with adverse events, including ROR 24 , PRR 25 , MGPS 26 , and BCPNN 27 . AEs that come up to a positive threshold for at least one approach are regarded as potential AEs. Supplementary Table S8 elaborates on the two-by-two contingency tables. Supplementary Table S9 presents the formulas and thresholds for these disproportionation analyses. The time interval between the occurrence of an AE and the initiation of the administration of etrasimod was defined as the time of occurrence of an etrasimod-related AE. The time incidence of AEs was modeled using Weibull distribution. In this study, the database was analyzed using SAS 9.4 software for statistical analysis. Declarations Author Contribution Q.G. conceptualized the study, executed it, and analyzed the data; W.G. provided methodological support and drafted the manuscript; M.S. offered financial support and critically revised the manuscript. Data availability The data supporting the findings of this study are publicly available from FAERS database. Researchers can access the data through the FDA website (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html) . The use of FAERS data is subject to FDA’s terms and conditions, and researchers are responsible for compliance with applicable regulations. References Ordas, I., Eckmann, L., Talamini, M., Baumgart, D. C. & Sandborn, W. J. Ulcerative Colitis. Lancet . 380 , 1606-1619 (2012). Vermeire, S. et al. Impact of Prior Biologic Or Janus Kinase Inhibitor Therapy On Efficacy and Safety of Etrasimod in the Elevate Uc 52 and Elevate Uc 12 Trials. J. Crohns Colitis . 18 , 1780-1794 (2024). Peyrin-Biroulet, L. et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (Stride): Determining Therapeutic Goals for Treat-to-Target. Am. J. Gastroenterol. 110 , 1324-1338 (2015). Le Berre, C., Honap, S. & Peyrin-Biroulet, L. Ulcerative Colitis. Lancet . 402 , 571-584 (2023). Voelker, R. What is Ulcerative Colitis? Jama. 331 , 716 (2024). Vermeire, S. et al. Long-Term Safety and Efficacy of Etrasimod for Ulcerative Colitis: Results From the Open-Label Extension of the Oasis Study. J. Crohns Colitis . 15 , 950-959 (2021). Hla, T. & Brinkmann, V. Sphingosine 1-Phosphate (S1P): Physiology and the Effects of S1P Receptor Modulation. Neurology . 76 , S3-S8 (2011). Glassner, K., Fan, C., Irani, M. & Abraham, B. P. Therapeutic Potential of Etrasimod in the Management of Moderately-to-Severely Active Ulcerative Colitis: Evidence to Date. Clin. Exp. Gastroenterol. 17 , 337-345 (2024). Al-Shamma, H. et al. The Selective Sphingosine 1-Phosphate Receptor Modulator Etrasimod Regulates Lymphocyte Trafficking and Alleviates Experimental Colitis. J. Pharmacol. Exp. Ther. 369 , 311-317 (2019). Kiyomi, K., Caroline, L., Lisette, A., Kye, G. & John, G. P045 Effect of Etrasimod On Circulating Lymphocyte Subsets: Data From a Randomized Phase 1 Study in Healthy Japanese and Caucasian Men. Am. J. Gastroenterol. 115 , S12 (2020). Shirley, M. Etrasimod: First Approval. Drugs . 84 , 247-254 (2024). Sandborn, W. J. et al. Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients with Ulcerative Colitis. Gastroenterology . 158 , 550-561 (2020). Sandborn, W. J. et al. Etrasimod as Induction and Maintenance Therapy for Ulcerative Colitis (Elevate): Two Randomised, Double-Blind, Placebo-Controlled, Phase 3 Studies. Lancet . 401 , 1159-1171 (2023). Takeuchi, K. et al. Efficacy and Safety of Etrasimod in Patients with Ulcerative Colitis in Japan: Data From the Phase 3 Elevate Uc 12 and Elevate Uc 40 Japan Trials. Digestion . 1-9 (2024). Knapp, D. E., Zax, B. B., Rossi, A. C. & O'Neill, R. T. A Method for Post-Marketing Screening of Adverse Reactions to Drugs: Initial Results. Drug Intell Clin Pharm . 14 , 23-27 (1980). Zhu, B. K. et al. Real-World Pharmacovigilance Study of Drug-Induced Autoimmune Hepatitis From the Faers Database. Sci. Rep. 15 , 4783 (2025). Al, S. E. et al. Differences in the Adverse Event Burden of Corticosteroid Use in Inflammatory Bowel Disease as Reported Between Adverse Event Reporting Systems and a Patient Questionnaire. J. Crohns Colitis . 19 , (2025). Gao, W. et al. Adverse Events in the Nervous System Associated with Blinatumomab: A Real-World Study. Bmc Med. 23 , 72 (2025). Vermeire, S. et al. Cardiovascular Events Observed Among Patients in the Etrasimod Clinical Programme: An Integrated Safety Analysis of Patients with Moderately to Severely Active Ulcerative Colitis. Bmj Open Gastroenterol. 12 , (2025). Dubinsky, M. C. et al. Low Incidence of Macular Edema and Other Ocular Events in the Etrasimod Development Program. J. Crohns Colitis . (2024). Peyrin-Biroulet, L. et al. Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 Elevate Uc Clinical Programme. J. Crohns Colitis . 18 , 1270-1282 (2024). Yuan, X. et al. Depression and Anxiety in Patients with Active Ulcerative Colitis: Crosstalk of Gut Microbiota, Metabolomics and Proteomics. Gut Microbes . 13 , 1987779 (2021). Zhang, J. et al. Psychological Symptoms and Quality of Life in Patients with Inflammatory Bowel Disease in China: A Multicenter Study. United European Gastroenterol. J. 12 , 374-389 (2024). Rothman, K. J., Lanes, S. & Sacks, S. T. The Reporting Odds Ratio and its Advantages Over the Proportional Reporting Ratio. Pharmacoepidemiol. Drug Saf. 13 , 519-523 (2004). Evans, S. J., Waller, P. C. & Davis, S. Use of Proportional Reporting Ratios (Prrs) for Signal Generation From Spontaneous Adverse Drug Reaction Reports. Pharmacoepidemiol. Drug Saf. 10 , 483-486 (2001). Rivkees, S. A. & Szarfman, A. Dissimilar Hepatotoxicity Profiles of Propylthiouracil and Methimazole in Children. J. Clin. Endocrinol. Metab. 95 , 3260-3267 (2010). Ang, P. S., Chen, Z., Chan, C. L. & Tai, B. C. Data Mining Spontaneous Adverse Drug Event Reports for Safety Signals in Singapore - A Comparison of Three Different Disproportionality Measures. Expert Opin. Drug Saf. 15 , 583-590 (2016). Additional Declarations No competing interests reported. Supplementary Files Supplementary.docx Cite Share Download PDF Status: Published Journal Publication published 21 Oct, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 14 Apr, 2025 Reviews received at journal 13 Apr, 2025 Reviews received at journal 31 Mar, 2025 Reviewers agreed at journal 22 Mar, 2025 Reviewers agreed at journal 20 Mar, 2025 Reviewers invited by journal 19 Mar, 2025 Editor assigned by journal 19 Mar, 2025 Editor invited by journal 19 Mar, 2025 Submission checks completed at journal 18 Mar, 2025 First submitted to journal 09 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6187859","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":432479340,"identity":"c1587a60-afa0-487c-b35c-da4144453c93","order_by":0,"name":"Qian Guo","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Qian","middleName":"","lastName":"Guo","suffix":""},{"id":432479341,"identity":"efbd3f0d-3707-4358-b826-64934203fa14","order_by":1,"name":"Meirong Shan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIie3Pv4rCQBDH8ZHA2iymHVH0FQYEjwMfZhdhr/EgZQpBJcducfouKe38E0gscr2FRdJcHbsrrlBrJYmdxX7q+cJvACzrBbF+lJwLGs02ZrHIhD+tTlrIlIOeaoQ8CihL4+qkh3wIvNg3QvzQ7fzLqTGso1WGtHXeUGpfzhm45luUJ90oIY9O7H2Z66NcdwHTn7A8ASUQ6ZdDIq9JyoDwsyqZEHKKELZSe1I7NRKcDG8J0UFqqJfweDxAUqK93AUo0phX/tI3wS4v/kfCbZr8/OdPe65ZlSd3+HPnlmVZ1kMXfjZNwitsqgEAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":true,"prefix":"","firstName":"Meirong","middleName":"","lastName":"Shan","suffix":""},{"id":432479342,"identity":"ba57642e-1fa0-43c4-b9dc-e2fb23a628eb","order_by":2,"name":"Wei Gao","email":"","orcid":"","institution":"The First Affiliated Hospital of Zhengzhou University","correspondingAuthor":false,"prefix":"","firstName":"Wei","middleName":"","lastName":"Gao","suffix":""}],"badges":[],"createdAt":"2025-03-09 09:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6187859/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6187859/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-19679-z","type":"published","date":"2025-10-21T16:16:58+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79575298,"identity":"17da0cf8-2b83-43b2-97e3-8238f4d98c43","added_by":"auto","created_at":"2025-03-31 11:14:16","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13572,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual and quarterly distribution of etrasimod AE reports.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/1ce5aff4a948629c501800d6.jpg"},{"id":79575304,"identity":"24a19965-91fd-4d55-b8b8-ef156b25ef97","added_by":"auto","created_at":"2025-03-31 11:14:16","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":20525,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence curve of adverse events in etrasimod treatment, highlighting the early risk period.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/7b1d3ef02b52ca05765de998.jpg"},{"id":79577999,"identity":"c313cdff-5c1e-468c-a039-acc1674c5fe8","added_by":"auto","created_at":"2025-03-31 11:30:16","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":55778,"visible":true,"origin":"","legend":"\u003cp\u003eProportion of adverse events by system organ class for etrasimod, showing the relative proportions across 27 SOC categories.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/a73499e249c451b13b9924f0.jpg"},{"id":79576575,"identity":"5617053c-9c80-4a89-9001-32acc01d822e","added_by":"auto","created_at":"2025-03-31 11:22:16","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":89838,"visible":true,"origin":"","legend":"\u003cp\u003eTop 50 adverse events by frequency at the PT level for etrasimod.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/f59f394294ea39a8fd314efa.jpg"},{"id":79575327,"identity":"ad3a0018-78e3-4390-a247-fc9cde40ae68","added_by":"auto","created_at":"2025-03-31 11:14:17","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":58915,"visible":true,"origin":"","legend":"\u003cp\u003eTime to onset of adverse events induced by etrasimod.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/942470e817e38e6888dc38f3.jpg"},{"id":79575319,"identity":"915137bd-eb8c-45d1-b97e-a1def065ab96","added_by":"auto","created_at":"2025-03-31 11:14:17","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":31530,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence curve of adverse events in etrasimod treatment, highlighting the early risk period\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/d3a2e03b9490acd373cf6760.jpg"},{"id":79576572,"identity":"5da78807-6d43-4099-83dd-84581a652329","added_by":"auto","created_at":"2025-03-31 11:22:16","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":61413,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the adverse event analysis process for etrasimod using the FDA Adverse Event Reporting System database.\u003c/p\u003e","description":"","filename":"7.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/d9b8108b9e643eccdb7473e5.jpg"},{"id":94490455,"identity":"0f1d0095-6e34-4338-9bf3-e43a12e9c050","added_by":"auto","created_at":"2025-10-27 17:10:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1338732,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/baeda9bf-292e-4e79-9785-d0b4c083dfd9.pdf"},{"id":79575300,"identity":"524ddc4c-3ae0-40bb-99f9-57317f8030e4","added_by":"auto","created_at":"2025-03-31 11:14:16","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":95914,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementary.docx","url":"https://assets-eu.researchsquare.com/files/rs-6187859/v1/98c2c5c87d357b4adf394fe2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Real-World Safety Profile of Etrasimod in the Treatment of Ulcerative Colitis: A Comprehensive Analysis from FAERS Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUlcerative colitis (UC) is an idiopathic chronic inflammatory disease of the colonic mucosa, starting in the rectum and typically extending proximally in a continuous manner, involving part or the entire colon\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. UC is characterized by rectal bleeding, diarrhea, urgency, and tenesmus and these symptoms are associated with a diminished quality of life\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. The goal of UC treatment is to achieve and maintain long-term clinical and endoscopic remission\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. It is caused by a combination of genetic predisposition and environmental factors, leading to alterations in the gut microbiota and interactions with the immune system\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. UC is characterized by alternating periods of active inflammation and remission. By 2023, the global prevalence of UC is estimated to be 5\u0026nbsp;million cases annually\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Patients with UC report a reduced quality of life due to symptoms such as diarrhea and rectal haemorrhage, as well as increased rates of depression, anxiety, sleep disturbances, and sexual dysfunction. The risk of developing colorectal cancer in UC patients 20 years after diagnosis is 4.5%, which is 1.7 times higher than that of the general population\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. The goals of UC treatment include achieving long-term, sustained clinical and endoscopic remission, and avoiding surgical resection of the affected colon\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSphingosine 1-phosphate (S1P) and its receptors (S1PRs) are involved in the pathogenesis of various immune-mediated inflammatory diseases. S1P regulates the trafficking of T cells and B cells, and its binding to the S1P1 receptor reversibly sequesters specific lymphocyte subsets within lymph nodes, leading to a reduction in peripheral immune cells and contributing to immune-related diseases such as UC\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e; \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Therefore, S1PR modulators offer a novel therapeutic option for UC patients. Etrasimod is a novel, small-molecule, oral S1PR1 receptor modulator, currently under clinical development for the treatment of immune-mediated inflammatory diseases, including UC\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Dose-dependent relationships between etrasimod plasma concentrations and lymphocyte counts have been observed in mice, and long-term use of the drug has been found to reduce inflammation in mouse models of colitis\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Additionally, research has found that analysis of lymphocyte subsets indicates etrasimod can reduce pro-inflammatory immune cells and functions as a selective immunomodulator rather than a broad-spectrum immunosuppressant\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. This drug was first approved in the United States in October 2023 for the treatment of adults with moderate to severe active UC\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn several Phase II and III randomized, double-blind, placebo-controlled trials targeting adult patients with moderate to severe active UC, the oral dose of 2mg etrasimod demonstrated greater efficacy than placebo in clinical and endoscopic improvements and was generally well-tolerated\u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Furthermore, the short-term safety of etrasimod was confirmed in these Phase II and III clinical trials. In a long-term open-label extension (OLE) study, adult patients with moderate to severe active UC who took 2mg of etrasimod once daily for 52 weeks showed good tolerance, with no treatment-related serious infections or new safety signals observed\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The OLE study provided support for the long-term safety and sustained clinical efficacy of etrasimod in treating adult patients with moderate to severe active UC.\u003c/p\u003e \u003cp\u003eThe FDA Adverse Event Reporting System (FAERS) is a database maintained by the FDA to collect and analyze post-marketing safety data on drugs and therapeutic biologics\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. This database is used to monitor the safety of marketed drugs and biologics, identify potential AEs, and support FDA regulatory decisions\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. AEs and medication error reports in the database are voluntarily submitted by healthcare professionals (such as doctors, pharmacists, nurses, etc.) and consumers\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. For over a decade, FAERS has been widely used to identify drug AEs, such as 22 drugs significantly associated with the risk of autoimmune hepatitis\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e and neurological adverse events associated with blinatumumab\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. The aim of this study is to describe etrasimod-related AEs by extracting relevant data from FAERS using various analytical methods. By evaluating the real-world safety of etrasimod, it can provide guidance for clinicians on safe medication use.\u003c/p\u003e \u003cp\u003eIn conclusion, etrasimod provides a new treatment option for moderate to severe UC. However, a detailed evaluation of its safe use is necessary. This study aims to provide evidence for clinical safety by investigating post-marketing adverse drug events (ADEs) of etrasimod using the FAERS database.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eAnnual and quarterly distribution of etrasimod AE reports\u003c/h2\u003e \u003cp\u003eFrom September 2023 to December 2024, the FDA received a total of 1,406 AE reports related to etrasimod as the PS. Statistical results indicate that the number of AE reports increased quarter by quarter, with the specific distribution shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDescriptive analysis\u003c/h3\u003e\n\u003cp\u003eThis study collected 663 AE reports from the FAERS database between 2004 and 2024, in which etrasimod was identified as the PS for the AEs. We drilled down further analysis on these data to explore the drug's safety profile. Among the reports, females accounted for 44.65%, while males accounted for 42.23%. The distribution varied by age, with the largest proportion being 18\u0026ndash;44 years old (36.8%), followed by 45\u0026ndash;64 years old (30.02%). The majority of AE reports were submitted in 2024, attaining 98.64%. Consumers were the primary reporters, representing 43.29% of the reports. The reports mainly originated from the United States (95.17%), followed by Canada (2.87%). Excluding cases with unknown severity, the most common serious AE was hospitalization (4.68%), followed by death (0.3%). In terms of the temporal distribution of adverse reactions, excluding cases with uncertain onset times, the highest incidence of adverse reactions occurred within 30 days (3.92%). Further descriptive results are provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of adverse event reports related to etrasimod from the FAERS database (Q4 2023\u0026ndash;Q4 2024).\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003e Characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u0026nbsp;of\u0026nbsp;cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProportion\u0026nbsp;of\u0026nbsp;cases\u0026nbsp;(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber\u0026nbsp;of\u0026nbsp;events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e663\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.65\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45\u0026ndash;64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e143\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eReporting\u0026nbsp;year\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2023\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e654\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eTop\u0026nbsp;4\u0026nbsp;reporting\u0026nbsp;countries\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAmerica\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e631\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePuerto\u0026nbsp;Rico\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eReporter\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsumer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e287\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e221\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eSevere outcomes in etrasimod\u003c/h3\u003e\n\u003cp\u003eAmong the 1,406 AE reports related to etrasimod, there were a total of 560 serious outcomes, including hospitalization (4.68%), disability (0.3%), and other outcomes (34.84%). Details are shown in the Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eDistribution of AEs at the SOC level\u003c/h3\u003e\n\u003cp\u003eAE reports related to etrasimod were documented in 24 out of 27 SOC categories. The distribution of these AEs is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Significant findings included general disorders and administration site conditions, gastrointestinal diseases, eye disorders, nervous system diseases, infections and infestations, skin and subcutaneous tissue disorders, musculoskeletal and connective tissue disorders, mental disorders, immune system disorders, circulatory and respiratory system disorders, blood and lymphatic system disorders, liver and bile system disorders, etc. Although the drug affects a wide range of organ systems, many SOC categories were found to have no statistically significant association with etrasimod (as illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSignal strength of etrasimod related adverse events across system organ classes (SOCs) in the FDA Adverse Event Reporting System database.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOCs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u0026nbsp;of\u003c/p\u003e \u003cp\u003ecases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR\u003c/p\u003e \u003cp\u003e(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR\u0026nbsp;(χ2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEBGM\u003c/p\u003e \u003cp\u003e(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC\u003c/p\u003e \u003cp\u003e(IC025)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral\u0026nbsp;disorders\u0026nbsp;and\u0026nbsp;administration\u0026nbsp;site\u0026nbsp;conditions*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.59(1.41,1.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.44(58.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.44(1.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.53(0.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u0026nbsp;disorders*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.36(2.06,2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.12(162.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.12(1.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.08(0.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEye\u0026nbsp;disorders*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.18(4.34,6.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.78(408.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.78(4.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.26(1.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNervous\u0026nbsp;system\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00(0.83,1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.00(0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.00(-0.28)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetabolism\u0026nbsp;and\u0026nbsp;nutrition\u0026nbsp;disorders*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.49(2.85,4.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.31(166.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.31(2.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.73(1.40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvestigations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.11(0.90,1.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.10(0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.10(0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.14(-0.17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfections\u0026nbsp;and\u0026nbsp;infestations\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.75(0.57,0.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.76(4.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.76(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.40(-0.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin\u0026nbsp;and\u0026nbsp;subcutaneous\u0026nbsp;tissue\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.61(0.45,0.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62(11.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.62(0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.69(-1.10)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjury,\u0026nbsp;poisoning\u0026nbsp;and\u0026nbsp;procedural\u0026nbsp;complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.25(0.18,0.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.27(86.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.27(0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.87(-2.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMusculoskeletal\u0026nbsp;and\u0026nbsp;connective\u0026nbsp;tissue\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.52(0.38,0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.54(16.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54(0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.90(-1.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychiatric\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.32(0.21,0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.33(37.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.33(0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.60(-2.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmune\u0026nbsp;system\u0026nbsp;disorders*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.56(1.04,2.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.55(4.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.55(1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.63(0.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.62(0.41,0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62(5.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.62(0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.68(-1.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory,\u0026nbsp;thoracic\u0026nbsp;and\u0026nbsp;mediastinal\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.31(0.20,0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32(32.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.32(0.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.66(-2.23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVascular\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.70(0.45,1.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.70(2.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.70(0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.51(-1.11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal\u0026nbsp;and\u0026nbsp;urinary\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.44(0.25,0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.45(8.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.45(0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.16(-1.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood\u0026nbsp;and\u0026nbsp;lymphatic\u0026nbsp;system\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.33(0.17,0.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.34(10.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.34(0.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.57(-2.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatobiliary\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.54(0.26,1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.54(2.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54(0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.88(-1.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical\u0026nbsp;and\u0026nbsp;medical\u0026nbsp;procedures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.31(0.14,0.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32(9.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.32(0.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.66(-2.61)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEar\u0026nbsp;and\u0026nbsp;labyrinth\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.82(0.34,1.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.82(0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.82(0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.29(-1.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoplasms\u0026nbsp;benign,\u0026nbsp;malignant\u0026nbsp;and\u0026nbsp;unspecified\u0026nbsp;(incl\u0026nbsp;cysts\u0026nbsp;and\u0026nbsp;polyps)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.13(0.06,0.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.14(28.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.14(0.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-2.88(-3.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEndocrine\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.40(0.58,3.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.40(0.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.40(0.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.48(-0.79)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReproductive\u0026nbsp;system\u0026nbsp;and\u0026nbsp;breast\u0026nbsp;disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.32(0.12,0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.32(5.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.32(0.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-1.64(-2.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial\u0026nbsp;circumstances\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15(0.02,1.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.15(4.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.15(0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-2.71(-3.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAsterisks (*) indicate statistically significant signals. Abbreviations: ROR, reporting odds ratio; PRR, proportional reporting ratio; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of the 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of the 95% confidence interval of the IC.\u003c/p\u003e\n\u003ch3\u003eDistribution of AEs at the PT level\u003c/h3\u003e\n\u003cp\u003eAnalysis of AEs at the PT level included ranking etrasimod-related AEs by frequency and evaluating positive signals. Figure\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e displays the 50 most common adverse reactions and known adverse reactions, which include hypertension, bradycardia, dyspnea, and macular edema. Moreover, potential adverse reactions not listed on the label were identified, such as type 2 diabetes mellitus (T2DM), diabetic eye disease, headache, dizziness, fatigue, malaise, diarrhea, nausea, UC, hematochezia, rash, and others. Details of these findings are exhibited in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Comprehensive information on all AEs meeting the positive signal criteria can be found in Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 50 most frequent adverse events for etrasimod at the preferred term (PT) level.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase Numbers\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR (χ2)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEBGM (EBGM05)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC (IC025)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug ineffective*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.91(3.22,4.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.68(219.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.68(3.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.88(1.56)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 2 diabetes mellitus*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e108.17(86.41,135.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e101.99(8084.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e101.73(81.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e6.67(5.18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetic eye disease*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7232.24(5526.88,9463.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6897.94(381415)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5869.72(4485.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e12.52(5.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCondition aggravated*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.27(5.42,9.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.07(240.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.06(5.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.82(2.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeadache*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.07(2.26,4.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.00(58.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.00(2.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.59(1.08)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.86(2.01,4.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.81(37.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.81(1.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.49(0.91)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFatigue*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.73(1.20,2.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.71(8.97)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.71(1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.77(0.22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiarrhoea*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.82(1.24,2.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.81(9.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.81(1.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.85(0.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalaise*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.58(1.75,3.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.55(24.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.55(1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.35(0.71)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColitis ulcerative*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25.01(16.56,37.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.62(521.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e24.60(16.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.62(3.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.29(0.86,1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.29(1.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.29(0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.36(-0.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOff label use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.20(0.79,1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.19(0.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.19(0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.26(-0.36)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug interaction*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.86(3.81,9.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.79(83.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e5.79(3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.53(1.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematochezia*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.34(11.27,26.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17.10(318.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17.09(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.10(2.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRectal haemorrhage*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.24(9.92,26.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.06(226.06)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.06(9.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.01(2.39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.06(0.64,1.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.06(0.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.06(0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.08(-0.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTherapeutic product effect incomplete*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6.23(3.74,10.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.17(65.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e6.17(3.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.63(1.49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColitis*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.03(10.06,28.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.87(209.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e16.87(9.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.08(2.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVision blurred*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.57(2.70,7.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.54(38.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.54(2.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.18(1.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.27(0.74,2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.27(0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.27(0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.35(-0.46)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasopharyngitis*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.93(1.66,5.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.91(15.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.91(1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.54(0.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypersensitivity*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.64(1.46,4.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.63(11.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.63(1.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.39(0.37)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePyrexia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.39(0.77,2.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.39(1.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.39(0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.47(-0.41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetic retinopathy*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e129.62(69.52,241.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128.71(1263.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e128.29(68.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7.00(2.48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate decreased*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.27(6.58,22.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.19(102.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.18(6.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.61(1.72)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.97(0.50,1.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.97(0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.97(0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.04(-0.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBradycardia*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.28(3.78,14.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.24(48.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.24(3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.86(1.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal disorder*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.34(1.74,6.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.33(14.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e3.33(1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.73(0.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.52(0.76,3.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.52(1.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.52(0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.60(-0.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdominal pain upper\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.74(0.87,3.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.73(2.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.73(0.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.79(-0.29)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlopecia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.79(0.89,3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.78(2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.78(0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.83(-0.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsthenia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.93(0.46,1.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.93(0.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.93(0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.10(-1.06)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstipation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.68(0.84,3.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.68(2.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.68(0.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.75(-0.32)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug hypersensitivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.79(0.89,3.58)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.78(2.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.78(0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.83(-0.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnoea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.62(0.31,1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.62(1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.62(0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.69(-1.59)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequent bowel movements*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13.88(6.93,27.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13.80(95.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e13.80(6.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.79(1.54)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.66(0.83,3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.66(2.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.66(0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.73(-0.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammation*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.13(3.56,14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7.10(41.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e7.10(3.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.83(1.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIllness*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.27(2.13,8.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.26(19.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e4.26(2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.09(0.68)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMacular oedema*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56.20(26.73,118.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e55.93(377.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e55.85(26.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.80(1.81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDefaecation urgency*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41.04(18.40,91.55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e40.87(233.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e40.83(18.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.35(1.52)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspepsia*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.74(1.23,6.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.73(6.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.73(1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.45(0.04)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeling abnormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.06(0.48,2.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.06(0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.06(0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.09(-1.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoaesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.73(0.77,3.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.72(1.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.72(0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.79(-0.45)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflammatory bowel disease*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e26.41(11.84,58.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e26.30(145.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.28(11.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.72(1.42)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePruritus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.70(0.31,1.56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.70(0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.70(0.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.52(-1.55)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisual impairment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.09(0.94,4.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.08(3.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.08(0.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e1.06(-0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.57(0.25,1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.57(1.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.57(0.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e-0.81(-1.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood cholesterol abnormal*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47.33(19.66,113.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e47.16(225.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e47.11(19.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.56(1.26)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood pressure abnormal*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.44(4.75,27.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11.40(47.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e11.40(4.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.51(0.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAsterisks (*) indicate statistically significant signals. Abbreviations: ROR, reporting odds ratio; PRR, proportional reporting ratio; EBGM, empirical Bayesian geometric mean; EBGM05, the lower limit of the 95% confidence interval of EBGM; IC, information component; IC025, the lower limit of the 95% confidence interval of the IC.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis of etrasimod-related AEs\u003c/h2\u003e \u003cp\u003eSubgroup analysis revealed that among the 50 most common AEs meeting the positive signal criteria, no gender-specific AEs were identified. However, adverse events related to hepatobiliary dysfunction (elevated liver enzymes, hepatic cysts, cholangitis, cholecystitis, cholelithiasis, hepatocellular injury, and hepatitis) were found exclusively in males. Detailed data are provided in Supplementary Tables S2 and S3. Only two adverse event reports involved patients under the age of 18, including colitis and lymphocyte count decreased. Among patients aged 18\u0026ndash;44, the 50 most common positive AEs included T2DM, haematochezia, UC, diarrhea, nausea, diabetic retinopathy, rectal haemorrhage, hypersensitivity, and abdominal pain. In the 45\u0026ndash;64 age group, AEs mainly contained T2DM, nausea, diarrhea, UC, rectal haemorrhage, hypersensitivity, constipation, haematochezia, rash, hypertension, and diabetic retinopathy. For patients\u0026thinsp;\u0026ge;\u0026thinsp;65, common AEs covered diarrhea, rash, rectal haemorrhage, colitis, nausea, hypersensitivity, and haematochezia. (Detailed information can be found in Supplementary Tables S4-S7).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eAnalysis of the onset time and weibull distribution of etrasimod AEs\u003c/h3\u003e\n\u003cp\u003eAnalysis of onset time of AEs during treatment with etrasimod showed that most AEs occurred within the first 30 days of treatment, except for reports of unknown onset time (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The cumulative incidence curve of AEs is displayed in Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e. The weibull distribution analysis indicated the early failure mode, and the results showed that the median time to onset (TTO) of AEs was 41 days (IQR: 0\u0026ndash;43 days). The scale parameters (α) and shape parameters (β) are 44.13 (95% CI: 26.67\u0026ndash;73.03) and 0.75 (95% CI: 0.57\u0026ndash;0.99), respectively. Detailed parameters are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAnalysis of time to onset of etrasimod-related adverse events and Weibull distribution.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eTime\u0026nbsp;to\u0026nbsp;onset\u0026nbsp;(days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e \u003cp\u003eWeibull\u0026nbsp;distribution\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase\u0026nbsp;reports\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u0026nbsp;(IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eScale\u0026nbsp;parameter:\u0026nbsp;α\u0026nbsp;(95%\u0026nbsp;CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eShape\u0026nbsp;parameter:\u0026nbsp;β\u0026nbsp;(95%CI)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEtrasimod\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41(0\u0026ndash;43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44.13\u0026nbsp;\u0026nbsp;(95%\u0026nbsp;CI:\u0026nbsp;26.67\u0026ndash;73.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.75\u0026nbsp;(95%\u0026nbsp;CI:\u0026nbsp;0.57\u0026ndash;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEarly\u0026nbsp;failure\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eUsing real-world data from the FAERS database, this study comprehensively evaluated the AEs following the marketing of etrasimod in 2023. The study confirmed adverse reactions already identified on the label such as hypertension, bradycardia, dyspnea, and macular edema. In addition, unlabeled adverse events were found including T2DM, diabetic eye disease, gastrointestinal disorders (diarrhea, nausea, UC, hematochezia), neurological disorders (headache, dizziness), fatigue, rash, hypersensitivity reactions, etc. These findings suggest the necessity of drug safety monitoring and provide clinicians with more comprehensive risk management information. Among 527 patients treated with etrasimod in the ELEVATE UC 52 and ELEVATE UC 12 trials, a total of 9 bradycardia events (1.7%) and 3 asymptomatic atrioventricular block events (0.6%) were reported\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. In the placebo-controlled UC cohort, the proportion of hypertension-associated treatment-emergent adverse events (TEAEs) and IR were numerically higher in patients receiving etrasimod (n = 15 (2.6%) IR 5.31 (95% CI 2.62–7.99) vs placebo (n = 4 (1.3%) IR 3.40 (95% CI 0.07 to 6.72)\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. And 14 patients (2.4%) receiving etrasimol were assessed as hypertensive AE of special interest (AESI)\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In the placebo-controlled UC cohort, two patients developed macular edema (0.3%; IR: 0.70) \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. The AEs on the label are consistent with our findings.\u003c/p\u003e \u003cp\u003eOur study also revealed AEs that are not currently listed on the drug label, with the most common AEs in etrasimod's Phase III clinical trial being headache and dizziness, with an incidence of ≥ 5%. Additionally in the open-label extension (OLE) of OASIS study, 60% of patients treated with etrasimod 2mg experienced AEs(67/112), and 94.4% of the AEs were mild or moderate severity\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. In the OLE the most common TEAEs are the worsening UC and anemia and their percentages were 19% and 11%, respectively\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. Furthermore, in ELEVATE UC 52 and ELEVATE UC UC 12 study, among all isolated proctitis patients, the most common TEAEs in ≥ 4% of patients receiving etrasimod included headaches, arthralgia, and increased blood creatine phosphokinase\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, among patients with more extensive colitis, the most common TEAEs were headache, worsening UC and pyrexia\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Patients with isolated proctitis had no liver damage, pulmonary disease, malignancy, or macular edema, whereas patients with more extensive colitis treated with etrasimod suffered from these AEs\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, these unlisted AEs should be closely monitored, and clinicians should carefully evaluate the situation of patients to determine the administration time; avoid adverse reactions caused by too long medication time, and try to achieve the best therapeutic effect within the full course of treatment. Otherwise regular review of colonoscopy, electrocardiogram, blood routine, liver function, etc., can detect some AEs earlier, and timely adjust the treatment to avoid serious AEs.\u003c/p\u003e \u003cp\u003ePatients with UC have a high prevalence of mental disorders such as depression and anxiety\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. A multi-center study from China showed that the proportion of mental disorders in IBD patients was 7.69%, among which UC patients had a higher prevalence of anxiety and depression compared with CD patients\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. The treatment of UC by etrasimod may result in worsening UC, which may lead to or aggravate mental disorders. In addition, In addition, attention should be paid to other adverse reactions caused by etrasimod, such as dizziness and headache. Such non-fatal AEs will affect the treatment compliance and adversely affect the therapeutic effect. Therefore, effective treatment of UC can significantly improve patients' quality of life.\u003c/p\u003e \u003cp\u003eIn this study, we conducted a temporal analysis of AEs, and predicted the time period of AEs according to Weibull distribution. And their results highlight the importance of monitoring, especially during the first month of etrasimod treatment. Frequent clinical follow-up within the first month is recommended, and early monitoring is essential to detect and prevent potential adverse reactions. Patients are encouraged to report early symptoms of AEs in a timely manner, thereby optimizing patient compliance and safety with the aim of improving overall patient outcomes.\u003c/p\u003e \u003cp\u003eThe research also found differences in certain SOCs, with no statistically significant signals observed. Reasons for this outcome may be multifaceted. Primarily, it could be attributed to the disproportionality analysis method, which evaluates adverse event reporting rates relative to the entire FAERS database rather than raw frequencies. Moreover, the broad nature of SOCs may dilute overall statistical significance, even if differences exist in specific AEs within a category. In addition, the pharmacological targets of drugs may span multiple system organs, leading to counteracting effects that obscure statistically significant signals. Furthermore, similarities in patients' baseline characteristics and high baseline reporting rates for certain SOCs could also diminish statistical differences.\u003c/p\u003e \u003cp\u003eIt should be noted that this study has several limitations. First, the FAERS database relies on a voluntary reporting mechanism, which may lead to underreporting or overreporting by those using the system. For example, severe AEs or those with high media attention may be frequently reported, while milder AEs may be overlooked. Second, there are issues of data incompleteness and data entry errors, such as missing critical information in reports (e.g., medical history, drug dosage, severity of symptoms, etc.). Third, although the dataset analyzed in this study includes multiple reports, it remains limited in scope, and a larger dataset is needed to validate our findings. Fourth, reporting heterogeneity also plays a role, as differences in reporting habits among individuals and uneven distribution of medical resources may introduce bias into the data. Finally, disproportionality analysis is used to identify positive signals of AEs, but it has limitations in establishing a causal relationship between etrasimod and AEs. To address these limitations, technical approaches (such as data cleaning and machine learning), integration of multiple data sources, international collaboration, and improvements in reporting mechanisms can be employed. Additionally, combining real-world evidence and epidemiological studies can further enhance the reliability and practicality of the data. Therefore, long-term prospective studies are still needed to confirm the potential adverse reactions identified.\u003c/p\u003e \u003cp\u003eIn summary, this study utilized the FAERS database to conduct a comprehensive analysis of real-world AEs associated with etrasimod, particularly focusing on reports since 2023. The findings confirmed known adverse reactions listed on the label, while also identifying potential AEs not mentioned on the label, such as T2DM, diabetic eye disease, worsening UC, dizziness, headache, fatigue, diarrhea, nausea, bloody stools, rash, and others. Additionally, subgroup analysis and temporal analysis revealed the populations most susceptible to AEs and the time periods during which these events were most likely to occur. These results provide crucial safety information for clinicians using etrasimod in the future, enabling better optimization of treatment plans and ultimately improving patient outcomes.\u003c/p\u003e "},{"header":"Methods","content":"\u003ch2\u003eData extraction\u003c/h2\u003e\u003cp\u003eThe raw data used in this study were obtained from the FAERS database, which is publicly available on the official website of the U.S. FDA (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html\u003c/span\u003e\u003cspan address=\"https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The database has been accessible since the first quarter of 2004 and is updated and released quarterly. For this study, the raw ASCII data packages were downloaded for data mining and statistical analysis. The search term used was 'etrasimod. The FAERS database consists of seven distinct data files, including demographic and administrative information (DEMO), detailed drug information (DRUG), drug indications (INDI), reported adverse events (REAC), patient outcomes (OUTC), report sources (RPSR), and drug therapy (THER).\u003c/p\u003e\u003ch2\u003eRecords screened\u003c/h2\u003e\u003cp\u003eDuplicate reports were removed based on the FDA-recommended deduplication method. The PRIMARYID, CASEID, and FDA_DT fields from the DEMO table were selected, and the data were sorted by CASEID, FDA_DT, and PRIMARYID. For reports with the same CASEID, the one with the largest FDA_DT value was retained. If both CASEID and FDA_DT were identical, the report with the largest PRIMARYID value was kept.\u003c/p\u003e\u003ch2\u003eData processing\u003c/h2\u003e\u003cp\u003eIn the DEMO data, a total of 22,375,298 AEs related to etrasimod were recorded. After excluding duplicate records (n = 3,761,306), the final number of DEMO records was determined to be 18,613,992. By screening the drug data (n = 66,418,951), we identified reports where etrasimod was considered the primary suspect drug (PS), excluding data related to secondary suspect (SS) and concomitant (C) drugs. Combined with the REAC data (n = 55,357,463), a total of 1406 AEs were ultimately confirmed as primarily associated with etrasimod as the PS. AEs in the FAERS database are reported from Preferred Term (PT), Advanced Group Term (HLGT), Advanced Term (HLT), System Organ Category (SOC), and Lowest Level Term (LLT) according to the Medical Dictionary for Regulatory Activities (MedDRA). The detailed steps for filtering etrasimod-related data from FAERS are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e \u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eDescriptive analysis was applied to depict reports of adverse events associated with etrasimod. Four disproportionation analyses were employed to examine the association of etrasimod with adverse events, including ROR\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, PRR\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, MGPS\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, and BCPNN\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. AEs that come up to a positive threshold for at least one approach are regarded as potential AEs. Supplementary Table S8 elaborates on the two-by-two contingency tables. Supplementary Table S9 presents the formulas and thresholds for these disproportionation analyses. The time interval between the occurrence of an AE and the initiation of the administration of etrasimod was defined as the time of occurrence of an etrasimod-related AE. The time incidence of AEs was modeled using Weibull distribution. In this study, the database was analyzed using SAS 9.4 software for statistical analysis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eQ.G. conceptualized the study, executed it, and analyzed the data; W.G. provided methodological support and drafted the manuscript; M.S. offered financial support and critically revised the manuscript.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are publicly available from FAERS database. Researchers can access the data through the FDA website (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html) . The use of FAERS data is subject to FDA\u0026rsquo;s terms and conditions, and researchers are responsible for compliance with applicable regulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrdas, I., Eckmann, L., Talamini, M., Baumgart, D. C. \u0026amp; Sandborn, W. J. Ulcerative Colitis. \u003cem\u003eLancet\u003c/em\u003e. \u003cstrong\u003e380\u003c/strong\u003e, 1606-1619 (2012).\u003c/li\u003e\n\u003cli\u003eVermeire, S. et al. Impact of Prior Biologic Or Janus Kinase Inhibitor Therapy On Efficacy and Safety of Etrasimod in the Elevate Uc 52 and Elevate Uc 12 Trials. \u003cem\u003eJ. Crohns Colitis\u003c/em\u003e. \u003cstrong\u003e18\u003c/strong\u003e, 1780-1794 (2024).\u003c/li\u003e\n\u003cli\u003ePeyrin-Biroulet, L. et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (Stride): Determining Therapeutic Goals for Treat-to-Target. \u003cem\u003eAm. J. 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L. \u0026amp; Tai, B. C. Data Mining Spontaneous Adverse Drug Event Reports for Safety Signals in Singapore - A Comparison of Three Different Disproportionality Measures. \u003cem\u003eExpert Opin. Drug Saf.\u003c/em\u003e\u003cstrong\u003e15\u003c/strong\u003e, 583-590 (2016).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Etrasimod, Ulcerative colitis, FAERS, Disproportionality analysis","lastPublishedDoi":"10.21203/rs.3.rs-6187859/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6187859/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEtrasimod is a sphingosine 1-phosphate (S1P) receptor modulator that selectively activates S1P receptor subtypes 1, 4, and 5, but exhibits no detectable activity on S1P2 and S1P3. It is primarily used for the treatment of ulcerative colitis (UC). There has been limited research on the adverse events (AEs) associated with etrasimod during its use in treating UC, necessitating a comprehensive and real-world evaluation of its clinical safety. This study aims to assess the AEs of etrasimod in UC patients using data from the FDA Adverse Event Reporting System (FAERS) database. By analyzing all AEs in the FAERS database since 2004, the safety of etrasimod in clinical applications was evaluated. Based on the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinkage (MGPS), we employed disproportionality analysis to identify all adverse event reports associated with etrasimod in clinical application. Additionally, this study utilized standardized MedDRA queries to identify AEs related to etrasimod. Our research provides real-world evidence on the safety profile of etrasimod, which is crucial for clinicians to safeguard patient health.\u003c/p\u003e","manuscriptTitle":"Evaluating the Real-World Safety Profile of Etrasimod in the Treatment of Ulcerative Colitis: A Comprehensive Analysis from FAERS Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:14:11","doi":"10.21203/rs.3.rs-6187859/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-14T09:06:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-13T15:02:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-31T15:37:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"15647989089492430291407503079000698906","date":"2025-03-22T13:37:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332142137696523064481854537675762019412","date":"2025-03-20T05:59:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-20T00:46:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-20T00:44:37+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-03-19T04:17:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-18T09:07:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-09T09:23:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6caa5bf5-1e7b-4fde-bf0b-a2f372cf94a8","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":46063240,"name":"Biological sciences/Drug discovery/Drug safety"},{"id":46063241,"name":"Health sciences/Diseases"}],"tags":[],"updatedAt":"2025-10-27T16:27:12+00:00","versionOfRecord":{"articleIdentity":"rs-6187859","link":"https://doi.org/10.1038/s41598-025-19679-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-10-21 16:16:58","publishedOnDateReadable":"October 21st, 2025"},"versionCreatedAt":"2025-03-31 11:14:11","video":"","vorDoi":"10.1038/s41598-025-19679-z","vorDoiUrl":"https://doi.org/10.1038/s41598-025-19679-z","workflowStages":[]},"version":"v1","identity":"rs-6187859","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6187859","identity":"rs-6187859","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}