BACKGROUND & AIMS Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302.

中文翻译：

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Etrasimod在溃疡性结肠炎患者的2期随机试验中的疗效和安全性。

背景与目的Etrasimod（APD334）是一种针对免疫介导的炎症性疾病的口服选择性鞘氨醇1-磷酸受体调节剂。我们评估了依拉西莫在中度至重度活动性溃疡性结肠炎（UC）患者中的疗效和安全性。方法在第2阶段的概念验证，双盲，平行组研究中，成人Mayo临床评分（MCSs）（粪便频率，直肠出血和内镜检查结果）修改为4-9，内窥镜评分为2或更多，直肠出血评分为1或1以上被随机分配到每天一次给予伊曲西莫1 mg（n = 52），伊曲西莫2 mg（n = 50）或安慰剂（n = 54）的组，持续12周。该研究于2015年10月15日至2018年2月14日在17个国家/地区的87个中心进行。主要终点是从基线到第12周改良MCS的平均改善程度增加。次要终点包括从基线到第12周内镜改善（分数低于1或更少）的患者比例。文章中对此进行了报道，尽管该研究在统计学上仅能得出主要终点的结论。结果在第12周，依曲西莫2 mg组达到了主要终点和所有次要终点。与安慰剂相比，Etrasimod 2 mg导致改良MCS的平均改善较基线显着增加（与安慰剂的差异为0.99点； 90％置信区间为0.30-1.68； P = 0.009），Etrasimod 1 mg导致增加与安慰剂相比，改良型MCS与基线相比的平均改善幅度为0.43点（置信区间为90％，减少0.24，增加1.11；标称P = 0.15）。接受伊曲西莫2 mg的患者的内镜改善发生率为41.8％，而接受安慰剂的患者为17.8％（P = 0.003）。大多数不良事件为轻度至中度。3例患者出现短暂，无症状的低度房室传导阻滞，可自发解决，所有患者在服用依曲西莫之前均有房室传导阻滞的迹象。结论在中度至重度溃疡性结肠炎患者中，伊曲西莫2 mg在改善临床和内镜方面比安慰剂更有效。有必要进行进一步的临床开发。Clinicaltrials.gov，编号：NCT02447302。大多数不良事件为轻度至中度。3例患者出现短暂，无症状的低度房室传导阻滞，可自发解决，所有患者在服用依曲西莫之前均有房室传导阻滞的迹象。结论在中度至重度溃疡性结肠炎患者中，伊曲西莫2 mg在改善临床和内镜方面比安慰剂更有效。有必要进行进一步的临床开发。Clinicaltrials.gov，编号：NCT02447302。大多数不良事件为轻度至中度。3例患者出现短暂，无症状的低度房室传导阻滞，可自发解决，所有患者在服用依曲西莫之前均有房室传导阻滞的迹象。结论在中度至重度溃疡性结肠炎患者中，伊曲西莫2 mg在改善临床和内镜方面比安慰剂更有效。有必要进行进一步的临床开发。Clinicaltrials.gov，编号：NCT02447302。埃曲西莫2 mg在改善临床和内镜方面比安慰剂更有效。有必要进行进一步的临床开发。Clinicaltrials.gov，编号：NCT02447302。埃曲西莫2 mg在改善临床和内镜方面比安慰剂更有效。有必要进行进一步的临床开发。Clinicaltrials.gov，编号：NCT02447302。