奥扎莫德用于溃疡性结肠炎的诱导缓解和维持治疗。
Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis.
机构信息
From the University of California San Diego, La Jolla (W.J.S.); Western University, London, ON, Canada (B.G.F.); the Inflammatory Bowel Disease Center, Academic Medical Center, Amsterdam (G.D.); the Center for Crohn's Disease and Ulcerative Colitis, Atlanta Gastroenterology Associates, Atlanta (D.C.W.); the Division of Gastroenterology, University Hospital Medical Center Bežanijska Kosa, Belgrade, Serbia (I.J.); the Feinberg School of Medicine, Chicago (S.B.H.); APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland (S.G.); Bristol Myers Squibb, Princeton, NJ (A.P., S.Y.H., J.H.L., L.C., D.C., K.U.); the Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York (J.-F.C.); Yale School of Medicine, New Haven, and the Veterans Affairs Connecticut Healthcare System, West Haven - both in Connecticut (L.L.); and IRCCS Humanitas Research Hospital and University Vita-Salute San Raffaele, Milan (S.D.).
出版信息
N Engl J Med. 2021 Sep 30;385(14):1280-1291. doi: 10.1056/NEJMoa2033617.
BACKGROUND
Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease.
METHODS
We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.92 mg of ozanimod) or placebo once daily in a double-blind manner, and patients in cohort 2 received open-label ozanimod at the same daily dose. At 10 weeks, patients with a clinical response to ozanimod in either cohort underwent randomization again to receive double-blind ozanimod or placebo for the maintenance period (through week 52). The primary end point for both periods was the percentage of patients with clinical remission, as assessed with the three-component Mayo score. Key secondary clinical, endoscopic, and histologic end points were evaluated with the use of ranked, hierarchical testing. Safety was also assessed.
RESULTS
In the induction period, 645 patients were included in cohort 1 and 367 in cohort 2; a total of 457 patients were included in the maintenance period. The incidence of clinical remission was significantly higher among patients who received ozanimod than among those who received placebo during both induction (18.4% vs. 6.0%, P<0.001) and maintenance (37.0% vs. 18.5% [among patients with a response at week 10], P<0.001). The incidence of clinical response was also significantly higher with ozanimod than with placebo during induction (47.8% vs. 25.9%, P<0.001) and maintenance (60.0% vs. 41.0%, P<0.001). All other key secondary end points were significantly improved with ozanimod as compared with placebo in both periods. The incidence of infection (of any severity) with ozanimod was similar to that with placebo during induction and higher than that with placebo during maintenance. Serious infection occurred in less than 2% of the patients in each group during the 52-week trial. Elevated liver aminotransferase levels were more common with ozanimod.
CONCLUSIONS
Ozanimod was more effective than placebo as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. (Funded by Bristol Myers Squibb; True North ClinicalTrials.gov number, NCT02435992.).
背景
奥扎莫德是一种选择性鞘氨醇-1-磷酸受体调节剂，目前正在研究用于治疗炎症性肠病。
方法
我们进行了一项 3 期、多中心、随机、双盲、安慰剂对照试验，评估奥扎莫德在中度至重度活动性溃疡性结肠炎患者中的诱导和维持治疗作用。在 10 周的诱导期内，队列 1 的患者被随机分配接受每日一次口服奥扎莫德盐酸盐 1mg（相当于 0.92mg 奥扎莫德）或安慰剂，进行双盲治疗，队列 2 的患者接受开放标签奥扎莫德相同的每日剂量。在 10 周时，两组中对奥扎莫德有临床应答的患者再次进行随机分组，接受双盲奥扎莫德或安慰剂维持治疗（至第 52 周）。两个时期的主要终点均为临床缓解患者的百分比，采用三组分 Mayo 评分评估。关键次要临床、内镜和组织学终点采用分级、分层检验进行评估。同时评估安全性。
结果
在诱导期内，队列 1 纳入 645 例患者，队列 2 纳入 367 例患者；共有 457 例患者纳入维持期。与安慰剂相比，奥扎莫德治疗患者的临床缓解发生率在诱导期（18.4% vs. 6.0%，P<0.001）和维持期（37.0% vs. 18.5%[第 10 周应答者]，P<0.001）均显著更高。与安慰剂相比，奥扎莫德治疗患者的临床应答发生率在诱导期（47.8% vs. 25.9%，P<0.001）和维持期（60.0% vs. 41.0%，P<0.001）也显著更高。两个时期中，奥扎莫德治疗的所有其他关键次要终点均显著优于安慰剂。奥扎莫德诱导期和维持期感染（任何严重程度）的发生率与安慰剂相似，但维持期高于安慰剂。两组患者在 52 周试验期间，严重感染的发生率均不到 2%。奥扎莫德治疗患者的肝氨基转移酶水平升高更为常见。
结论
奥扎莫德作为中重度活动性溃疡性结肠炎患者的诱导和维持治疗药物，优于安慰剂。（由 Bristol Myers Squibb 资助；True North ClinicalTrials.gov 编号，NCT02435992。）
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