Background Etrasimod is an oral, once-daily (QD), selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). Unlike the other S1P receptor modulator approved for UC, etrasimod and its metabolites do not have a molecular structure to inhibit monoamine oxidase (MAO).1 Coadministration of drugs that inhibit MAO with opioids and antidepressants may increase the risk of adverse events (AEs), including hypertension.2 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 (NCT03945188) and ELEVATE UC 12 (NCT03996369) trials. Methods Safety data pooled from both trials were analysed in patients receiving etrasimod 2 mg QD (up to 52 weeks of exposure) with/without concomitant opioids or antidepressants. We report the proportions of patients who had ≥1 concurrent AE potentially related to serotonin syndrome, consisting of one standardised MedDRA Query, one query based on the Hunter Criteria and supplemental preferred terms (pyrexia, tachycardia and hypertension-related AEs).3 Results Among 527 patients receiving etrasimod, 77 (14.6%) and 35 (6.6%) patients were taking concomitant opioids or antidepressants, respectively. Most patients on concomitant opioids or antidepressants were White (80.0–88.3%); male (50.6–51.4%); their median age was 35.0 (18.0–70.0) and 41.0 (19.0–74.0) years, respectively. More patients with vs without concomitant opioids or antidepressants, respectively, consumed alcohol (40.3% vs 24.7% and 48.6% vs 25.4%) and used tobacco (40.3% vs 20.9% and 34.3% vs 23.0%). The incidence of other AEs potentially related to serotonin syndrome was low and generally comparable in all subgroups; reported rates of pyrexia and tachycardia were similar in patients with/without concomitant opioids or antidepressants (Table). Hypertension-related AEs were infrequent and generally balanced. No AEs per the Hunter Criteria were reported in patients on concomitant opioids or antidepressants (Table). No reported AEs were serious or led to treatment discontinuation among patients taking these concomitant medications. Conclusion The incidence of AEs was low and comparable in patients receiving etrasimod with or without concomitant opioids or antidepressants. This analysis 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. References 1. Lee CA et al. Clin Pharmacol Drug Dev 2023; 12: 553–571. 2. Sands BE et al. J Crohns Colitis 2023; online ahead of print. 3. Dunkley EJC et al. QJM 2003; 96: 635–642.

中文翻译：

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P524 Etrasimod 在溃疡性结肠炎患者中与阿片类药物或抗抑郁药同时使用后不良事件的风险较低

背景 Etrasimod 是一种口服、每日一次 (QD) 的选择性 1-磷酸鞘氨醇 (S1P)1,4,5 受体调节剂，用于治疗中度至重度活动性溃疡性结肠炎 (UC)。与批准用于 UC 的其他 S1P 受体调节剂不同，依曲莫德及其代谢物不具有抑制单胺氧化酶 (MAO) 的分子结构。1 抑制 MAO 的药物与阿片类药物和抗抑郁药共同给药可能会增加不良事件 (AE) 的风险， 2 这项事后分析评估了在 3 期 ELEVATE UC 52 (NCT03945188) 和 ELEVATE UC 12 (NCT03996369) 试验中服用 etrasimod 和同时服用阿片类药物或抗抑郁药的患者中与血清素综合征潜在相关的 AE 发生率。方法 对接受依拉莫德 2 mg QD（最长暴露 52 周）联合/不联合阿片类药物或抗抑郁药的患者分析两项试验汇总的安全性数据。我们报告了患有 ≥ 1 种可能与血清素综合征相关的并发 AE 的患者比例，其中包括一项标准化 MedDRA 查询、一项基于 Hunter 标准的查询和补充首选术语（发热、心动过速和高血压相关 AE）。3 结果527 名接受依曲莫德治疗的患者中，分别有 77 名（14.6%）和 35 名（6.6%）患者同时服用阿片类药物或抗抑郁药。大多数同时服用阿片类药物或抗抑郁药的患者是白人（80.0-88.3%）；男性（50.6–51.4%）；他们的中位年龄分别为 35.0 (18.0–70.0) 和 41.0 (19.0–74.0) 岁。与未同时服用阿片类药物或抗抑郁药的患者相比，饮酒（40.3% vs 24.7% 和 48.6% vs 25.4%）和吸烟（40.3% vs 20.9% 和 34.3% vs 23.0%）的患者比例更高。可能与血清素综合征相关的其他 AE 的发生率较低，并且在所有亚组中通常具有可比性；报告的发热和心动过速发生率在同时服用/不服用阿片类药物或抗抑郁药的患者中相似（表）。与高血压相关的 AE 并不常见，而且总体上是平衡的。根据亨特标准，在同时服用阿片类药物或抗抑郁药的患者中没有报告任何不良事件（表）。在服用这些联合药物的患者中，没有报告严重的或导致治疗中断的不良事件。结论 在接受依曲莫德联合或不联合阿片类药物或抗抑郁药治疗的患者中，AE 发生率较低且具有可比性。该分析支持艾曲莫德与 UC 患者常用药物（如阿片类药物或抗抑郁药）之间存在临床相关药物相互作用的可能性较低。参考文献 1. Lee CA 等人。临床药理学药物开发 2023；12：553-571。2. Sands BE 等人。J 克罗恩斯结肠炎 2023；印刷前在线。3. 邓克利 EJC 等人。QJM 2003; 96：635–642。