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.
J Crohns Colitis. 2024 Nov 4;18(11):1780-1794. doi: 10.1093/ecco-jcc/jjae079.
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.
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.
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.
Bio/JAKi-naïve and -experienced patients had clinically meaningful induction and maintenance treatment benefits with etrasimod vs placebo.
CLINICALTRIALS.GOV: NCT03945188; NCT03996369.
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。
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。
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]。
在 bio/JAKi 初治和有经验的患者中，与安慰剂相比，依特司莫具有临床意义的诱导和维持治疗获益。
NCT03945188；NCT03996369。
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