Afzali Anita, Regueiro Miguel, Yarur Andres J, Zabana Yamile, Ng Siew C, Menon Sujatha, McDonnell Aoibhinn, Lazin Krisztina, Keating Michael, Bhattacharjee Abhishek, Branquinho Diogo, Bananis Eustratios, Peyrin-Biroulet Laurent
Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA.
United European Gastroenterol J. 2025 Jun;13(5):719-727. doi: 10.1002/ueg2.12745. Epub 2025 Feb 1.
Etrasimod is an oral, once-daily (q.d.), selective sphingosine 1-phosphate (S1P) receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the S1P receptor modulator ozanimod, etrasimod does not have a molecular structure to inhibit monoamine oxidase (MAO). Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs).
This post hoc analysis evaluated the incidence of AEs potentially related to serotonin syndrome in patients taking etrasimod and concomitant opioids or antidepressants in the Phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.
Safety data pooled from both trials were analysed in subgroups of patients receiving etrasimod 2 mg q.d. (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥ 1 concurrent AE potentially associated with serotonin syndrome, including hypertension-related events.
Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) were taking concomitant opioids or antidepressants, respectively. The incidence of AEs potentially related to serotonin syndrome, including hypertension-related AEs, was low (≤ 8.6%) and generally comparable in all subgroups. No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications.
The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis further supports the low likelihood of clinically relevant drug-drug interactions between etrasimod and medications commonly prescribed to patients with UC, such as opioids or antidepressants. (ClinicalTrials.gov: NCT03945188; NCT03996369).
埃曲莫德是一种口服的、每日一次的选择性1 -磷酸鞘氨醇（S1P）受体调节剂，用于治疗中度至重度活动性溃疡性结肠炎（UC）。与S1P受体调节剂奥扎莫德不同，埃曲莫德没有抑制单胺氧化酶（MAO）的分子结构。抑制MAO的药物与阿片类药物和抗抑郁药合用可能会增加不良事件（AE）的风险。
这项事后分析评估了在3期ELEVATE UC 52和ELEVATE UC 12试验中，服用埃曲莫德并同时服用阿片类药物或抗抑郁药的患者中，可能与5-羟色胺综合征相关的AE的发生率。
对两项试验汇总的安全性数据进行分析，这些数据来自接受2mg每日一次埃曲莫德（暴露时间长达52周）且服用/未服用阿片类药物或抗抑郁药的患者亚组。我们报告了发生≥1种可能与5-羟色胺综合征相关的并发AE（包括高血压相关事件）的患者比例。
在527例接受埃曲莫德治疗的患者中，分别有77例（14.6%）和35例（6.6%）同时服用阿片类药物或抗抑郁药。可能与5-羟色胺综合征相关的AE（包括高血压相关AE）的发生率较低（≤8.6%），并且在所有亚组中总体相当。在服用这些联合药物的患者中，未报告的AE是严重的，也未导致治疗中断。
接受埃曲莫德治疗的患者中，无论是否同时服用阿片类药物或抗抑郁药，AE的发生率都较低且相当。该分析进一步支持了埃曲莫德与UC患者常用药物（如阿片类药物或抗抑郁药）之间发生临床相关药物相互作用的可能性较低。（ClinicalTrials.gov：NCT03945188；NCT03996369）
Zotero 插件