近日，美国西奈山伊坎医学院Bruce E. Sands小组联合德国施莱斯维格荷斯坦大学医院Stefan Schreiber研究组，比较了维多珠单抗和阿达木单抗治疗中重度溃疡性结肠炎的疗效。这一研究成果发表在2019年9月26日出版的《新英格兰医学杂志》上。

研究组在34个国家的245个中心进行了这项临床3b期、双盲、双模拟的随机试验，共招募了769名患者，将其随机分组，其中383名接受维多珠单抗治疗，在第1天和第2、6、14、22、30、38和46周注射300mg 维多珠单抗；386名接受阿达木单抗治疗，第一天注射40mg，第一周共注射160mg，第2周注射80mg，之后每2周注射40mg，持续至第50周。

在第52周，维多珠单抗组的临床缓解率和内窥镜改善率分别为31.3%和39.7%，均显著高于阿达木单抗组（22.5%和27.7%）。维多珠单抗组和阿达木单抗组中分别有12.6%和21.8%的患者出现无皮质类固醇临床缓解，差异不显著。维多珠单抗组和阿达木单抗组的暴露校正感染率分别为23.4和34.6次/100人年，严重感染率分别为1.6和2.2次/100人年。

综上，在治疗中重度活动性溃疡性结肠炎中，维多珠单抗在临床缓解和内窥镜改善方面显著优于阿达木单抗，但在无皮质类固醇临床缓解方面无优势。

据悉，溃疡性结肠炎患者广泛使用生物疗法，但这些疗法缺乏直接试验。

附：英文原文

Title: Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis

Author: Bruce E. Sands, Laurent Peyrin-Biroulet, Edward V. Loftus, Jr., Silvio Danese, Jean-Frédéric Colombel, Murat Trüner, Laimas Jonaitis, Brihad Abhyankar, Jingjing Chen, Raquel Rogers, Richard A. Lirio, Jeffrey D. Bornstein, Stefan Schreiber

Issue&Volume: Vol 381 No 13

Abstract: 

BACKGROUND
Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking.

METHODS
In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52.

RESULTS
A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P=0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, −9.3 percentage points; 95% CI, −18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years.

CONCLUSIONS
In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. 

DOI:10.1056/NEJMoa1905725

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905725