Yarur Andres J, Chiorean Michael V, Allegretti Jessica R, Cross Raymond K, Ha Christina, Goetsch Martina, McDonnell Aoibhinn, Dalam Alexis B, Wu Joseph, Blanco David A, Abbatemarco Arcangelo M, Panés Julian
Inflammatory Bowel Disease Institute and Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Inflammatory Bowel Disease Center, Swedish Medical Center, Seattle, WA, USA.
Inflamm Bowel Dis. 2024 Dec 13. doi: 10.1093/ibd/izae288.
Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy.
In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively. Oral CS or 5-ASA were allowed at baseline. Patients in the monotherapy subgroup received etrasimod or placebo without concomitant CS and/or 5-ASA at baseline. Predefined primary (clinical remission) and key secondary efficacy endpoints aligned with those from both trials and were assessed at Week 12 and Week 52. Safety was assessed up to Week 52.
Clinical remission rates at Weeks 12 and 52 were significantly higher for etrasimod compared with placebo in patients receiving monotherapy (Week 12: 26.2% vs 4.8%; Week 52: 35.7% vs 4.0%). Differences vs placebo were statistically significant for all predefined endpoints at both time points in patients receiving monotherapy or etrasimod with concomitant 5-ASA only (all P < .05); numerical differences, due to small sample sizes, vs placebo were observed for all endpoints in the CS only and CS + 5-ASA subgroups. Safety was consistent with the overall population.
Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or 5-ASA in patients receiving etrasimod.
NCT03945188; NCT03996369.
艾曲莫德是一种口服的、每日一次（QD）的选择性1,4,5-鞘氨醇-1-磷酸受体调节剂，用于治疗中度至重度活动性溃疡性结肠炎（UC）。我们评估了艾曲莫德单药治疗的益处以及联合使用皮质类固醇（CS）和/或5-氨基水杨酸（5-ASA）治疗的影响。
在ELEVATE UC 52和ELEVATE UC 12试验中，中度至重度活动性UC患者分别以2:1的比例随机接受2mg QD的艾曲莫德或安慰剂治疗52周和12周。基线时允许口服CS或5-ASA。单药治疗亚组的患者在基线时接受艾曲莫德或安慰剂，不联合CS和/或5-ASA。预定义的主要（临床缓解）和关键次要疗效终点与两项试验一致，并在第12周和第52周进行评估。安全性评估至第52周。
接受单药治疗的患者中，第12周和第52周时，艾曲莫德的临床缓解率显著高于安慰剂（第12周：26.2%对4.8%；第52周：35.7%对4.0%）。在接受单药治疗或仅联合5-ASA的艾曲莫德治疗的患者中，两个时间点所有预定义终点与安慰剂相比的差异均具有统计学意义（所有P<0.05）；由于样本量小，仅使用CS和CS + 5-ASA亚组的所有终点与安慰剂相比观察到数值差异。安全性与总体人群一致。
与安慰剂相比，艾曲莫德单药治疗显示出一致的疗效和安全性；接受艾曲莫德治疗的患者联合使用CS和/或5-ASA未观察到明显益处。
NCT03945188；NCT03996369。
