Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils de Lyon, Université Claude Bernard Lyon1, INSERM U1111, CIRI, Centre International de Recherche en Infectiologie, Lyon, France.
Univ. Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation, Lille, France.
Am J Gastroenterol. 2022 Sep 1;117(9):1482-1490. doi: 10.14309/ajg.0000000000001842. Epub 2022 Jun 2.
The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance.
We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic.
At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26.
In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.
本研究旨在描述英夫利昔单抗（IFX）在因疗效丧失或不耐受而停药后重新用于克罗恩病（CD）的疗效和安全性。
我们进行了一项前瞻性多中心观察性队列研究，纳入了 6 个月以上停用 IFX 后临床（CD 活动指数＞150）和客观存在肠道活动的 CD 成年患者。初始停药的原因可能是继发疗效丧失或 IFX 不耐受。重新开始的方案包括在系统预处理后第 0、4 和 8 周给予 3 次 IFX 输注。主要终点是在第 26 周时 IFX 重新治疗的疗效，定义为 CD 活动指数＜150，且未停用 IFX 或使用皮质类固醇、手术或其他生物制剂。
在 69 例分析患者中，24 例（35%）在第 26 周达到主要终点。在先前出现 LOR（n=48）和 IFX 不耐受（n=21）的患者中，第 26 周时达到临床缓解的比例无显著差异（35%和 33%，P=0.87）。在 27 例患者中记录了 32 次急性输注反应，导致 20 例患者停用 IFX。在第 4 周检测到阳性抗药物抗体，但无基线药代动力学特征，可预测第 26 周 IFX 失败或输注反应。
在这项首个前瞻性队列研究中，无论停药的原因如何，三分之一的 CD 患者重新使用 IFX 是安全有效的。早期检测抗药物抗体可预测随后的 IFX 重新引入失败和输注反应。
