Disher Tim, Naessens Dominik, Sanon Myrlene, Bonner Ashley, Ellis Jenna, Bartlett Meaghan, Hooper Becky, Yang Zijiang, Allegretti Jessica R, Dignass Axel
EVERSANA Value & Evidence Services, Burlington, ON, Canada.
Janssen Pharmaceutica N.V., Beerse, Belgium.
Adv Ther. 2025 Jun;42(6):2708-2727. doi: 10.1007/s12325-025-03183-x. Epub 2025 May 6.
This study used network meta-analysis (NMA) to evaluate the comparative efficacy of available advanced therapies for moderately to severely active Crohn's disease (CD) versus the IL-23 inhibitor guselkumab.
A systematic literature review was conducted to identify randomized controlled trials (RCTs) of advanced therapies in moderately to severely active CD. Bayesian NMAs were conducted for outcomes of clinical response, clinical remission, endoscopic response, and a combined outcome of clinical remission with endoscopic response, at the end of the maintenance phase (up to 1 year). Primary analyses included patients with varied prior inadequate treatment responses, with additional analyses conducted for specific subgroups. Re-randomized trials were normalized in several cases to mimic a standard treat-through design, incorporating data from additional sources, when necessary, for patients who had an inadequate response or experienced a delayed response following induction.
Of the 58 RCTs identified, 13 with maintenance endpoint data were ultimately included in the NMAs. Guselkumab 100 mg and 200 mg were more likely to be effective versus several comparators. Guselkumab 200 mg demonstrated significantly greater efficacy versus infliximab 10 mg/kg every 8 weeks and upadacitinib 30 mg daily for clinical response and clinical remission. For endoscopic response, guselkumab 200 mg showed significantly greater efficacy than ustekinumab, adalimumab, and upadacitinib. Significance was also noted versus ustekinumab on the combined outcome of clinical remission with endoscopic response. Similarly, guselkumab 100 mg demonstrated efficacy versus comparators across analyses. Guselkumab achieved higher rankings based on surface under the cumulative ranking curve. Findings of primary analyses within mixed populations were generally corroborated by subpopulation analyses.
Results of this NMA in moderately to severely active CD indicate a higher likelihood of guselkumab achieving each clinical and endoscopic endpoint analyzed at the end of the maintenance phase versus other advanced therapies assessed.
本研究采用网络荟萃分析（NMA）来评估现有晚期疗法治疗中度至重度活动性克罗恩病（CD）相对于白细胞介素-23抑制剂古塞库单抗的疗效比较。
进行了一项系统的文献综述，以确定中度至重度活动性CD的晚期疗法的随机对照试验（RCT）。在维持阶段结束时（最长1年），针对临床缓解、临床应答、内镜应答以及临床缓解与内镜应答的综合结果进行贝叶斯网络荟萃分析。主要分析纳入了既往治疗反应不佳的不同患者，并对特定亚组进行了额外分析。在几种情况下，对重新随机化试验进行了标准化处理，以模拟标准的全程治疗设计，必要时纳入来自其他来源的数据，用于诱导后反应不佳或反应延迟的患者。
在确定的58项随机对照试验中，最终有13项具有维持终点数据的试验被纳入网络荟萃分析。100毫克和200毫克的古塞库单抗与几种对照药物相比更有可能有效。对于临床应答和临床缓解，200毫克的古塞库单抗相对于每8周10毫克/千克的英夫利昔单抗和每日30毫克的乌帕替尼显示出显著更高的疗效。对于内镜应答，200毫克的古塞库单抗比优特克单抗、阿达木单抗和乌帕替尼显示出显著更高的疗效。在临床缓解与内镜应答的综合结果方面，与优特克单抗相比也具有显著性。同样，100毫克的古塞库单抗在各项分析中与对照药物相比也显示出疗效。基于累积排名曲线下面积，古塞库单抗获得了更高的排名。混合人群中主要分析的结果在亚组分析中总体得到了证实。
这项针对中度至重度活动性CD的网络荟萃分析结果表明，与评估的其他晚期疗法相比，在维持阶段结束时，古塞库单抗达到每个分析的临床和内镜终点的可能性更高。
