瑞莎珠单抗与乌司奴单抗治疗中重度克罗恩病的疗效比较。

Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn's Disease.

机构信息

From the Department of Gastroenterology, INFINY Institute, INSERM NGERE, Centre Hospitalier Régional Universitaire de Nancy, Vandœuvre-lès-Nancy, France (L.P.-B.); the Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal (L.P.-B.), and the Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB (R.P.) - both in Canada; the Crohn's and Colitis Center at the Baton Rouge General and the GI Alliance, Baton Rouge, LA (J.C.C.); the Henry D. Janowitz Division of Gastroenterology, Department of Medicine (J.-F.C.), and the Susan and Leonard Feinstein IBD Center (M.D.), Icahn School of Medicine at Mount Sinai, New York; the Department of Pathophysiology and Transplantation, Università degli Studi di Milano and the Unit of Gastroenterology and Endoscopy, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano (F.C.), and Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele (S.D.) - both in Milan; the Department of Gastroenterology, Amsterdam University Medical Centers, Amsterdam (G.D.); the Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven (M.F.), and the Imelda GI Clinical Research Center, Department of Gastroenterology, Imelda General Hospital, Bonheiden (P.B.) - both in Belgium; the Department of Medicine I, University Hospital Schleswig-Holstein, Christian-Albrechts-University, Kiel (S.S.), the Department of Medicine 1, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (R.A.), and the Department of Gastroenterology, Infectious Diseases and Rheumatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin (B.S.) - all in Germany; the Centre for Immunobiology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London (J.O.L.), the Department of Gastroenterology, Guy's and St Thomas' NHS Foundation Trust (P.M.I.), and the School of Immunology and Microbial Sciences, King's College London (P.M.I.) - all in London; the Department of Gastroenterology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China (Q.C.); and AbbVie, North Chicago, IL (E.N., K.W., T.A., K.K., W.R.D., V.P., X.H., S.B., L.S.).

出版信息

N Engl J Med. 2024 Jul 18;391(3):213-223. doi: 10.1056/NEJMoa2314585.

DOI:10.1056/NEJMoa2314585

PMID:39018531

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. (Funded by AbbVie; ClinicalTrials.gov number, NCT04524611.).

摘要

背景

尚不清楚 risankizumab 与 ustekinumab 相比在克罗恩病患者中的疗效和安全性。

方法

在这项 3b 期、多中心、开放标签、随机、对照试验中，终点评估为盲法，中重度克罗恩病患者在抗 TNF 治疗中反应不足或不耐受此类治疗的副作用，随机接受 risankizumab 或 ustekinumab 标准剂量治疗 48 周。两个主要终点，按顺序进行测试，分别为第 24 周临床缓解（定义为克罗恩病活动指数评分<150[范围 0 至 600，分数越高表示疾病活动度越高]），该终点分析了完成第 24 周就诊的前 50%患者，非劣效性边界为 10 个百分点；和第 48 周内镜缓解（定义为评分≤4，与基线相比下降≥2 分，且任何单个变量的简单克罗恩病内镜评分无子评分>1[范围 0 至 56，分数越高表示疾病越严重]），该终点分析了 100%的患者的优势。所有接受至少一剂 risankizumab 或 ustekinumab 的患者均进行安全性评估。

结果

在疗效分析的全意向治疗人群中，接受 risankizumab 的 255 名患者中有 230 名（90.2%）和接受 ustekinumab 的 265 名患者中有 193 名（72.8%）完成了所有规定的治疗。两个主要终点均达到；risankizumab 在第 24 周的临床缓解方面不劣于 ustekinumab（58.6% vs. 39.5%；调整差异 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 ustekinumab（31.8% vs. 16.2%；调整差异 15.6 个百分点；95%CI 8.4 至 22.9；P<0.001）。两组不良反应的发生率似乎相似。

结论

在这项涉及因抗 TNF 治疗副作用不可接受或对此类治疗反应不足而患有中重度克罗恩病的患者的 risankizumab 和 ustekinumab 的头对头临床试验中，risankizumab 在第 24 周的临床缓解方面不劣于 ustekinumab，在第 48 周的内镜缓解方面优于 ustekinumab。（由 AbbVie 资助；ClinicalTrials.gov 编号，NCT04524611）。