Department of Gastroenterology and Hepatology, Copenhagen University Hospital-Herlev and Gentofte, Herlev, Denmark.
Gastrounit, Medical Section, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.
Aliment Pharmacol Ther. 2024 Jul;60(2):124-143. doi: 10.1111/apt.18110. Epub 2024 Jun 11.
Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA).
We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509).
Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses.
We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.
对于克罗恩病(CD)患者,先进疗法的起效速度可能是一个重要的决策参数,但目前缺乏对比评估。我们旨在通过网络荟萃分析(NMA)比较先进 CD 疗法的早期应答。
我们系统地检索了 MEDLINE、Embase 和 CENTRAL,截至 2024 年 2 月 19 日,以寻找随机对照试验。主要复合结局为治疗的前 6 周内诱导临床缓解(克罗恩病活动指数(CDAI)≤150)和临床应答(CDAI 降低≥100 分)。根据 PRISMA-NMA 指南(PROSPERO ID:CRD42022368509),我们纳入了在此时间点内的任何评估,采用贝叶斯随机效应 NMA 进行分析。
纳入了 25 项研究,共 7414 名患者。英夫利昔单抗联合硫唑嘌呤或单药治疗在 6 周内诱导临床缓解的效果最高,且明显优于certolizumab、ustekinumab、guselkumab、vedolizumab 和 upadacitinib。然而,与 risankizumab 600mg 和 adalimumab 160/80mg 相比,其优势并不显著。因此,英夫利昔单抗联合硫唑嘌呤和 guselkumab 600mg 在相应的临床应答分析中排名最高,但无统计学意义。在生物暴露的患者中,没有任何一种药物(包括英夫利昔单抗、upadacitinib 和 risankizumab)诱导出最高的临床应答。另一方面,vedolizumab、certolizumab 和 ustekinumab在所有分析中排名最低。
我们发现英夫利昔单抗的疗效排名最高,优于所有其他药物,但 risankizumab 和 adalimumab除外,其具有最高的早期缓解诱导概率。在生物暴露的患者中,upadacitinib 和 risankizumab 诱导出最高的临床应答。然而,英夫利昔单抗在这一人群中并未被研究。