Truong Steven L, Chin Jasmine, Liew David F L, Zahir Syeda Farah, Ryan Elizabeth G, Rubel Diana, Radford-Smith Graham, Robinson Philip C
Department of Medicine, Griffith University, Brisbane, QLD, Australia.
Coast Joint Care, Maroochydore, QLD, Australia.
Rheumatol Ther. 2021 Dec;8(4):1603-1616. doi: 10.1007/s40744-021-00360-6. Epub 2021 Aug 26.
The aim of this work is to perform a systematic review and meta-analysis of anti-tumor necrosis factor (anti-TNF) and anti-interleukin-17 (anti-IL-17) trials for spondyloarthritis, psoriatic arthritis, and psoriasis comparing rates of inflammatory bowel disease (IBD) events compared to placebo.
MEDLINE, EMBASE, and The Cochrane Library were searched for double-blind, randomized placebo-controlled anti-TNF and anti-IL-17 trials of included diseases. Inflammatory bowel disease events from the RCT period were pooled and meta-analyzed using statistical methods suitable for low-event-rate meta-analysis (Peto's, Mantel-Haenszel, hypergeometric-normal model, and Shuster-Guo-Skyler). When observed data were insufficient, we performed an exploratory sensitivity analysis to compare methods.
We identified 9551 original papers, and included 96 publications: 65 anti-TNF and 31 anti-IL-17 trials, containing 21 new and 12 flare IBD events in 28,209 participants. New IBD on anti-IL-17 occurred 0.23/100 patient-years (PY) in psoriasis, 0.61/100 PY in PsA and 1.63/100 PY in spondyloarthritis, rates similar to observational cohorts, and less commonly on anti-TNF (0/100 PY, 0/100 PY, 0.32/100 PY, respectively). No evidence of difference between groups was found, with wide CI from many pooled counts of zero, especially in placebo arms.
IBD events were rare, occurring at rates similar to biologic-naive groups. We could not find statistically significant differences in risk of new or recurrent IBD between treatment and control groups using selected meta-analytical methods for low event rate scenarios. Meta-analyses of this topic require more IBD events, ideally without pooling heterogeneous groups. Larger, thoroughly reported trials with systematic and detailed safety reporting are required to improve risk estimation and to make accurate inferences.
本研究旨在对治疗脊柱关节炎、银屑病关节炎和银屑病的抗肿瘤坏死因子（抗TNF）及抗白细胞介素-17（抗IL-17）试验进行系统评价和荟萃分析，比较与安慰剂相比炎症性肠病（IBD）事件的发生率。
检索MEDLINE、EMBASE和Cochrane图书馆，查找纳入疾病的双盲、随机安慰剂对照抗TNF和抗IL-17试验。汇总随机对照试验期间的炎症性肠病事件，并使用适用于低事件率荟萃分析的统计方法（Peto法、Mantel-Haenszel法、超几何正态模型和Shuster-Guo-Skyler法）进行荟萃分析。当观察数据不足时，我们进行探索性敏感性分析以比较不同方法。
我们识别出9551篇原始论文，纳入96篇出版物：65项抗TNF试验和31项抗IL-17试验，28209名参与者中发生21例新发和12例IBD病情复发事件。银屑病中抗IL-17治疗的新发IBD发生率为0.23/100患者年（PY），银屑病关节炎中为0.61/100 PY，脊柱关节炎中为1.63/100 PY，这些发生率与观察队列相似，而抗TNF治疗时发生率较低（分别为0/100 PY、0/100 PY、0.32/100 PY）。未发现组间差异的证据，许多汇总计数为零，置信区间较宽，尤其是在安慰剂组。
IBD事件罕见，发生率与未使用生物制剂的组相似。使用针对低事件率情况选择的荟萃分析方法，我们未发现治疗组和对照组在新发或复发性IBD风险上有统计学显著差异。该主题的荟萃分析需要更多IBD事件，理想情况下不合并异质性组。需要更大规模、报告详尽且有系统详细安全性报告的试验来改善风险估计并做出准确推断。
