基于既往对先进疗法反应不足或不耐受的司库奇尤单抗疗效和安全性：INSPIRE和COMMAND 3期研究的事后分析

Risankizumab efficacy and safety based on prior inadequate response or intolerance to advanced therapy: post hoc analysis of the INSPIRE and COMMAND phase 3 studies.

作者信息

Panaccione Remo, Louis Edouard, Colombel Jean-Frederic, D'Haens Geert, Peyrin-Biroulet Laurent, Dubinsky Marla, Takeuchi Ken, Rubin David T, Kalabic Jasmina, Chien Karen B, Chen Su, Cheng Ling, Zhang Yafei, Duan W Rachel, Vladea Ramona, Hecht Patrick M, Morisset Pierre, Schreiber Stefan, Ferrante Marc

机构信息

Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.

Hepato-Gastroenterology and Digestive Oncology Department, University Hospital CHU of Liège, Liège, Belgium.

出版信息

J Crohns Colitis. 2025 Jan 11;19(1). doi: 10.1093/ecco-jcc/jjaf005.

DOI:10.1093/ecco-jcc/jjaf005

PMID:39804294

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11772864/

Abstract

BACKGROUND AND AIMS

Treating ulcerative colitis (UC) in patients with prior advanced therapy (AT) exposure may be challenging. We report the efficacy and safety of risankizumab, a monoclonal interleukin 23p19 antibody, in patients with UC and prior inadequate response or intolerance to AT (AT-IR).

METHODS

In the 12-week phase 3 INSPIRE induction study, patients were randomized to intravenous risankizumab 1200 mg or placebo. Clinical responders were randomized to subcutaneous risankizumab 180 mg, risankizumab 360 mg, or placebo (risankizumab withdrawal) in the 52-week phase 3 COMMAND maintenance study. This post hoc analysis assessed outcomes by AT-IR status, number, and mechanism of action. AT included biologics, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.

RESULTS

Efficacy analyses included 472 non-AT-IR and 503 AT-IR patients (induction), and 137 non-AT-IR and 411 AT-IR patients (maintenance). More patients achieved clinical remission per Adapted Mayo score with risankizumab 1200 mg versus placebo at induction week 12 (non-AT-IR, 29.7% versus 8.4%, nominal P < .0001; AT-IR, 11.4% versus 4.3%, nominal P = .0083); consistent with risankizumab 180 mg or risankizumab 360 mg versus placebo (withdrawal) at maintenance week 52 (non-AT-IR, 50.9% or 61.7% versus 31.1%, nominal P = .057 or P = .0033, respectively; AT-IR, 36.6% or 29.5% versus 23.2%, nominal P = .0159 or P = .2334, respectively). Risankizumab had increased efficacy over placebo, regardless of AT-IR number or mechanism of action, with higher efficacy rates for non-AT-IR compared to AT-IR. Safety results in non-AT-IR and AT-IR patients were generally comparable in both induction and maintenance.

CONCLUSIONS

Risankizumab was effective and well tolerated, regardless of prior AT-IR status.

CLINICAL TRIAL REGISTRATION NUMBERS

INSPIRE [NCT03398148], COMMAND [NCT03398135].

摘要

背景与目的

治疗曾接受过晚期治疗（AT）的溃疡性结肠炎（UC）患者可能具有挑战性。我们报告了瑞莎珠单抗（一种单克隆白细胞介素23p19抗体）在UC患者且既往对AT反应不足或不耐受（AT-IR）患者中的疗效和安全性。

方法

在为期12周的3期INSPIRE诱导研究中，患者被随机分为静脉注射1200mg瑞莎珠单抗或安慰剂。临床缓解者在为期52周的3期COMMAND维持研究中被随机分为皮下注射180mg瑞莎珠单抗、360mg瑞莎珠单抗或安慰剂（停用瑞莎珠单抗）。这项事后分析按AT-IR状态、数量和作用机制评估结局。AT包括生物制剂、Janus激酶抑制剂和鞘氨醇-1-磷酸受体调节剂。

结果

疗效分析纳入了472例非AT-IR患者和503例AT-IR患者（诱导期），以及137例非AT-IR患者和411例AT-IR患者（维持期）。在诱导期第12周时，与安慰剂相比，1200mg瑞莎珠单抗组更多患者根据改良梅奥评分达到临床缓解（非AT-IR，29.7%对8.4%，名义P<0.0001；AT-IR，11.4%对4.3%，名义P=0.0083）；与维持期第52周时180mg瑞莎珠单抗或360mg瑞莎珠单抗组与安慰剂（停用）组情况一致（非AT-IR，分别为50.9%或61.7%对31.1%，名义P=0.057或P=0.0033；AT-IR，分别为36.6%或29.5%对23.2%，名义P=0.0159或P=0.2334）。无论AT-IR数量或作用机制如何，瑞莎珠单抗的疗效均高于安慰剂，非AT-IR患者的有效率高于AT-IR患者。非AT-IR和AT-IR患者在诱导期和维持期的安全性结果总体相当。