Division of Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital, San Diego, California; Department of Pediatrics, University of California, San Diego, La Jolla, California.
Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Clin Gastroenterol Hepatol. 2024 Jan;22(1):22-33.e6. doi: 10.1016/j.cgh.2023.08.039. Epub 2023 Sep 15.
BACKGROUND & AIMS: Withdrawal of immunomodulators (IMMs) or tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel diseases (IBDs) in remission on combination therapy is attractive. We evaluated the efficacy and safety of (1) IMM, or (2) TNF antagonist withdrawal in patients with IBD in sustained remission on combination therapy.
Through a systematic review till March 31, 2023, we identified randomized controlled trials (RCTs) that compared the efficacy and safety of IMM or TNF antagonist withdrawal vs continued combination therapy, in patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy. Primary outcome was risk of relapse and serious adverse events at 12 months. We conducted meta-analysis to calculate relative risk (RR) and 95% confidence interval (CI) and used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence.
We identified 8 RCTs with 733 patients (77% with Crohn's disease, 91% on infliximab-based combination therapy). On meta-analysis of 5 RCTs, there was no difference in the risk of relapse between patients with IMM withdrawal (continued TNF antagonist monotherapy) vs continued combination therapy (16.8% vs 14.9%; RR, 1.15; 95% CI, 0.75-1.76) without heterogeneity (low certainty of evidence). TNF antagonist withdrawal (continued IMM monotherapy) was associated with 2.4-times higher risk of relapse compared with continuing combination therapy (31.5% vs 11.2%; RR, 2.35; 95% CI, 1.38-4.01), with minimal heterogeneity (low certainty of evidence). There was no difference in the risk of serious adverse events with IMM or TNF antagonist withdrawal vs continued combination therapy.
In patients with IBD in sustained corticosteroid-free clinical remission for >6 months on combination therapy, de-escalation with TNF antagonist withdrawal, but not IMM withdrawal, was associated with an increased risk of relapse.
对于正在接受联合治疗且处于缓解期的炎症性肠病（IBD）患者，停用免疫调节剂（IMM）或肿瘤坏死因子（TNF）拮抗剂具有吸引力。我们评估了（1）在联合治疗中持续缓解且无皮质类固醇的 IBD 患者中停用 IMM，或（2）TNF 拮抗剂停药的疗效和安全性。
通过系统综述，我们检索了截至 2023 年 3 月 31 日的随机对照试验（RCT），比较了 IMM 或 TNF 拮抗剂停药与继续联合治疗在联合治疗中持续缓解且无皮质类固醇的 IBD 患者中的疗效和安全性，这些患者在联合治疗中持续缓解且无皮质类固醇超过 6 个月。主要结局是 12 个月时复发和严重不良事件的风险。我们进行了荟萃分析以计算相对风险（RR）和 95%置信区间（CI），并使用推荐评估、制定与评价（GRADE）方法评估证据的确定性。
我们共确定了 8 项 RCT，涉及 733 名患者（77%为克罗恩病，91%接受英夫利昔单抗为基础的联合治疗）。对 5 项 RCT 的荟萃分析显示，停用 IMM（继续 TNF 拮抗剂单药治疗）与继续联合治疗的患者之间复发风险无差异（16.8% vs 14.9%；RR，1.15；95%CI，0.75-1.76），无异质性（低确定性证据）。与继续联合治疗相比，TNF 拮抗剂停药（继续 IMM 单药治疗）与更高的复发风险相关（31.5% vs 11.2%；RR，2.35；95%CI，1.38-4.01），异质性极小（低确定性证据）。与继续联合治疗相比，停用 IMM 或 TNF 拮抗剂与严重不良事件风险无差异。
在联合治疗中持续缓解且无皮质类固醇超过 6 个月的 IBD 患者中，TNF 拮抗剂停药而非 IMM 停药与复发风险增加相关。
