在 ELEVATE UC 52 和 ELEVATE UC 12 试验中，先前的生物制剂或 Janus 激酶抑制剂治疗对依特司莫单抗疗效和安全性的影响。

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.

机构信息

Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

J Crohns Colitis. 2024 Nov 4;18(11):1780-1794. doi: 10.1093/ecco-jcc/jjae079.

DOI:10.1093/ecco-jcc/jjae079

PMID:38877972

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11532610/

Abstract

BACKGROUND AND AIMS

Etrasimod is an oral, once daily, selective, sphingosine 1-phosphate [S1P]1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis [UC]. This subgroup analysis evaluated the efficacy and safety of etrasimod 2 mg once daily vs placebo by prior biologic/Janus kinase inhibitor [bio/JAKi] exposure in ELEVATE UC 52 and ELEVATE UC 12.

METHODS

Pre-defined efficacy endpoints were assessed at Weeks 12 and 52 in ELEVATE UC 52 and Week 12 in ELEVATE UC 12 in bio/JAKi-naïve and -experienced patients, and at Week 12 [pooled] based on prior advanced therapy exposure mechanism.

RESULTS

In the ELEVATE UC 52 and ELEVATE UC 12 analysis populations, 80/274 [29.2%] and 74/222 [33.3%] patients receiving etrasimod and 42/135 [31.1%] and 38/112 [33.9%] patients receiving placebo, respectively, were bio/JAKi-experienced. In both bio/JAKi-naïve and -experienced patients, a significantly greater proportion receiving etrasimod vs placebo achieved clinical remission [p < 0.05] in ELEVATE UC 52 at Weeks 12 [naïve: 30.9% vs 9.7%; experienced: 17.5% vs 2.4%] and 52 [naïve: 36.6% vs 7.5%; experienced: 21.3% vs 4.8%]; in ELEVATE UC 12, this was observed only for bio/JAKi-naïve patients [naïve: 27.7% vs 16.2%, p = 0.033; experienced: 18.9% vs 13.2%, p = 0.349]. Similar patterns were observed for most efficacy endpoints. Among patients with prior anti-integrin exposure [N = 90], a significantly greater proportion achieved clinical response [54.1% vs 27.6%, p = 0.030], but not clinical remission [9.8% vs 3.4%, p = 0.248], with etrasimod vs placebo.

CONCLUSIONS

Bio/JAKi-naïve and -experienced patients had clinically meaningful induction and maintenance treatment benefits with etrasimod vs placebo.

CLINICALTRIALS.GOV: NCT03945188; NCT03996369.

摘要

背景和目的

依特司莫是一种每日口服一次的、选择性的、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期溃疡性结肠炎[UC]。这项亚组分析评估了依特司莫 2mg 每日一次与安慰剂在 ELEVATE UC52 和 ELEVATE UC12 中既往生物/Janus 激酶抑制剂[bio/JAKi]暴露患者中的疗效和安全性。

方法

在 ELEVATE UC52 和 ELEVATE UC12 中，根据既往先进治疗暴露机制，在第 12 周和第 52 周评估预定义的疗效终点，在第 12 周评估 ELEVATE UC12 中 bio/JAKi 初治和有经验患者的疗效终点。

结果

在 ELEVATE UC52 和 ELEVATE UC12 分析人群中，分别有 80/274[29.2%]和 74/222[33.3%]接受依特司莫治疗的患者以及 42/135[31.1%]和 38/112[33.9%]接受安慰剂治疗的患者有 bio/JAKi 暴露史。在 bio/JAKi 初治和有经验的患者中，与安慰剂相比，接受依特司莫治疗的患者在 ELEVATE UC52 中达到临床缓解的比例显著更高[P<0.05]，在第 12 周[初治：30.9% vs 9.7%；有经验：17.5% vs 2.4%]和第 52 周[初治：36.6% vs 7.5%；有经验：21.3% vs 4.8%]；在 ELEVATE UC12 中，仅观察到 bio/JAKi 初治患者出现这种情况[初治：27.7% vs 16.2%，P=0.033；有经验：18.9% vs 13.2%，P=0.349]。在大多数疗效终点中也观察到类似的模式。在既往抗整联蛋白暴露的患者中[N=90]，与安慰剂相比，接受依特司莫治疗的患者达到临床应答的比例显著更高[54.1% vs 27.6%，P=0.030]，但临床缓解的比例无显著差异[9.8% vs 3.4%，P=0.248]。