法国南锡大学Laurent Peyrin-Biroulet团队比较了利生奇珠单抗与乌司奴单抗治疗中重度克罗恩病的疗效与安全性。这一研究成果发表在2024年7月18日出版的《新英格兰医学杂志》上。

与乌司奴单抗相比，利生奇珠单抗在克罗恩病患者中的疗效和安全性尚不清楚。

在这项3b期、多中心、开放标签、随机、对照试验中，研究组对终点进行盲法评估，将对抗肿瘤坏死因子（TNF）治疗反应不足或此类治疗产生不可接受副作用的中重度克罗恩病患者随机分配接受标准剂量的利生奇珠单抗或乌司奴单抗治疗48周。按顺序测试的两个主要终点是第24周的临床缓解（定义为克罗恩病活动指数得分<150[范围，0至600，得分越高表示疾病活动越严重]），在完成第24周随访的前50%患者中进行分析，非劣效性界限为10个百分点；第48周内镜缓解（定义为评分≤4，比基线下降≥2分，克罗恩病简单内镜评分[范围，0至56，评分越高表示疾病越严重]的任何单个变量的子评分>1），分析100%患者的非劣效性。对所有接受至少一剂利生奇珠单抗或乌司奴单抗治疗的患者进行了安全性评估。

在疗效分析的全意向治疗人群中，接受利生奇珠单抗治疗的255名患者中有230名（90.2%）完成了所有指定的治疗，接受乌司奴单抗治疗的265名患者中也有193名（72.8%）完成了全部指定的治疗。两个主要终点都得到了满足；在第24周的临床缓解方面，利生奇珠单抗不劣于乌司奴单抗（58.6%对39.5%；校正后的差异为18.4个百分点；95%置信区间[CI]，6.6至30.3），在第48周的内镜缓解方面优于乌司奴单抗（31.8%对16.2%；校正后的差异为15.6个百分点，95%CI，8.4至22.9；P<0.001）。两组的不良事件发生率大致相似。

研究结果表明，在这项涉及中重度克罗恩病患者的利生奇珠单抗和乌司奴单抗的头对头临床试验中，这些患者在抗TNF治疗中出现了不可接受的副作用或对这种治疗的反应不足，利生奇珠单抗在第24周的临床缓解方面不劣于乌司奴单抗，在第48周的内窥镜缓解方面优于乌司奴单抗。

附：英文原文

Title: Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease

Author: Laurent Peyrin-Biroulet, J. Casey Chapman, Jean-Frederic Colombel, Flavio Caprioli, Geert D’Haens, Marc Ferrante, Stefan Schreiber, Raja Atreya, Silvio Danese, James O. Lindsay, Peter Bossuyt, Britta Siegmund, Peter M. Irving, Remo Panaccione, Qian Cao, Ezequiel Neimark, Kori Wallace, Toni Anschutz, Kristina Kligys, W. Rachel Duan, Valerie Pivorunas, Xiu Huang, Sofie Berg, Lei Shu, Marla Dubinsky

Issue&Volume: 2024-07-18

Abstract:

BACKGROUND

The efficacy and safety of risankizumab as compared with ustekinumab in patients with Crohn’s disease are unknown.

METHODS

In this phase 3b, multicenter, open-label, randomized, controlled trial with blinded assessment of end points, patients with moderate-to-severe Crohn’s disease who had had an inadequate response to anti–tumor necrosis factor (TNF) therapy or unacceptable side effects with such therapy were randomly assigned to receive risankizumab or ustekinumab at standard doses for 48 weeks. The two primary end points, which were tested sequentially, were clinical remission at week 24 (defined as a Crohn’s Disease Activity Index score of <150 [range, 0 to 600, with higher scores indicating more severe disease activity]), which was analyzed in the first 50% of patients to complete the week 24 visit, with a noninferiority margin of 10 percentage points; and endoscopic remission at week 48 (defined as a score of ≤4, a decrease of ≥2 points from baseline, and no subscore >1 in any individual variable on the Simple Endoscopic Score for Crohn’s Disease [range, 0 to 56, with higher scores indicating more severe disease]), which was analyzed for superiority in 100% of the patients. Safety was assessed in all patients who received at least one dose of risankizumab or ustekinumab.

RESULTS

In the full intention-to-treat population for the efficacy analysis, 230 of 255 patients (90.2%) who received risankizumab and 193 of 265 patients (72.8%) who received ustekinumab completed all the assigned treatments. Both primary end points were met; risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 (58.6% vs. 39.5%; adjusted difference, 18.4 percentage points; 95% confidence interval [CI], 6.6 to 30.3) and superior to ustekinumab with respect to endoscopic remission at week 48 (31.8% vs. 16.2%; adjusted difference, 15.6 percentage points; 95% CI, 8.4 to 22.9; P<0.001). The incidence of adverse events appeared to be similar in the two groups.

CONCLUSIONS

In this head-to-head clinical trial of risankizumab and ustekinumab involving patients with moderate-to-severe Crohn’s disease who had had unacceptable side effects with anti-TNF therapy or an inadequate response to such therapy, risankizumab was noninferior to ustekinumab with respect to clinical remission at week 24 and superior with respect to endoscopic remission at week 48.

DOI: NJ202407183910307

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2314585