Vermeire Séverine, Chiorean Michael, Panés Julián, Peyrin-Biroulet Laurent, Zhang Jinkun, Sands Bruce E, Lazin Krisztina, Klassen Preston, Naik Snehal U, Cabell Christopher H, Sandborn William J
Department of Gastroenterology & Hepatology, University Hospitals Leuven, Leuven, Belgium.
Division of Gastroenterology, Virginia Mason Medical Center, Seattle, WA, USA.
J Crohns Colitis. 2021 Jun 22;15(6):950-959. doi: 10.1093/ecco-jcc/jjab016.
Etrasimod is an oral, selective, sphingosine 1-phosphate receptor modulator. In a phase 2, randomised, double-blind, placebo-controlled trial in adults with moderately-to-severely active ulcerative colitis [OASIS], etrasimod 2 mg provided significant benefit versus placebo and was generally well tolerated. This open-label extension [OLE] evaluated safety and efficacy of etrasimod for up to 52 weeks.
In OASIS, 156 patients received etrasimod 1 mg, etrasimod 2 mg, or placebo, once daily for 12 weeks. After completing OASIS, patients could enrol in the OLE and receive etrasimod 2 mg for an additional 34-40 weeks.
In all, 118 patients enrolled in the OLE; 112 patients received etrasimod 2 mg at any point and were evaluated for safety and efficacy. A total of 92 [82%] patients who received etrasimod 2 mg in the OLE completed the study. Treatment-emergent adverse events occurred in 60% [67/112] of patients receiving etrasimod 2 mg at any time, most commonly worsening ulcerative colitis and anaemia; 94% of adverse events were mild/moderate. At end of treatment, 64% of patients met the criteria for clinical response, 33% for clinical remission, and 43% for endoscopic improvement. Week 12 clinical response, clinical remission, or endoscopic improvement was maintained to end of treatment in 85%, 60%, or 69% of patients, respectively. Steroid-free clinical remission occurred in 22% of overall patients.
In this long-term extension study, etrasimod 2 mg demonstrated a favourable safety profile. Most patients with clinical response, clinical remission, or endoscopic improvement at Week 12 maintained that status to end of treatment.
艾曲莫德是一种口服的选择性1-磷酸鞘氨醇受体调节剂。在一项针对中度至重度活动性溃疡性结肠炎成人患者的2期随机双盲安慰剂对照试验[OASIS]中，2mg艾曲莫德与安慰剂相比具有显著疗效，且总体耐受性良好。这项开放标签扩展试验[OLE]评估了艾曲莫德长达52周的安全性和疗效。
在OASIS试验中，156例患者接受1mg艾曲莫德、2mg艾曲莫德或安慰剂治疗，每日一次，为期12周。完成OASIS试验后，患者可参加OLE试验，并额外接受34 - 40周的2mg艾曲莫德治疗。
共有118例患者参加了OLE试验；112例患者在任何时间接受了2mg艾曲莫德治疗，并对其安全性和疗效进行了评估。在OLE试验中，共有92例（82%）接受2mg艾曲莫德治疗的患者完成了研究。在任何时间接受2mg艾曲莫德治疗的患者中，60%（67/112）出现了治疗中出现的不良事件，最常见的是溃疡性结肠炎恶化和贫血；94%的不良事件为轻度/中度。在治疗结束时，64%的患者达到临床缓解标准，33%达到临床缓解，43%达到内镜改善。分别有85%、60%或69%的患者在第12周时的临床缓解、临床缓解或内镜改善维持到治疗结束。22%的总体患者实现了无类固醇临床缓解。
在这项长期扩展研究中，2mg艾曲莫德显示出良好的安全性。大多数在第12周出现临床缓解、临床缓解或内镜改善的患者在治疗结束时维持了该状态。
