Department of Biomedical Sciences, Humanitas University, Milan, Italy.
Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy.
Clin Gastroenterol Hepatol. 2023 Apr;21(4):907-921.e2. doi: 10.1016/j.cgh.2022.07.032. Epub 2022 Aug 6.
BACKGROUND & AIMS: Safety is a key consideration when choosing advanced therapies (biologic agents and oral small-molecule inhibitors/modulators) in patients with inflammatory bowel diseases (IBDs). We performed a systematic review and meta-analysis comparing the risk of serious infections with advanced therapies in active comparator studies.
Through a systematic search until February 28, 2022, we included 20 head-to-head studies comparing risk of serious infections with tumor necrosis factor α (TNFα) antagonists, vedolizumab, ustekinumab, tofacitinib, filgotinib, and ozanimod in patients with IBD. We performed random-effects meta-analysis comparing different advanced therapies.
No significant difference was observed in the risk of serious infections between vedolizumab vs TNFα antagonists in all patients with IBD (17 cohorts: odds ratio [OR], 0.84; 95% CI, 0.68-1.04), with moderate heterogeneity (I = 37%); on subgroup analysis, vedolizumab was associated with a lower risk of serious infections in patients with ulcerative colitis (11 cohorts: OR, 0.68; 95% CI, 0.56-0.83; I = 0%), but not in Crohn's disease (CD) (9 cohorts: OR, 1.03; 95% CI, 0.78-1.35; I = 42%). Age, sex, prior biologic exposure, and use of biologic monotherapy did not influence this association. In patients with CD, ustekinumab was associated with a lower risk of serious infections vs TNFα antagonists (3 cohorts: OR, 0.49; 95% CI, 0.25-0.93; I = 16%) and vs vedolizumab (3 cohorts: OR, 0.40; 95% CI, 0.17-0.93; I = 67%). Few studies compared other advanced therapies.
Vedolizumab may offer net benefit over TNFα antagonists in patients with ulcerative colitis, but not in CD. Ustekinumab may offer net benefit over TNFα antagonists and vedolizumab in patients with CD.
在炎症性肠病（IBD）患者中，选择高级治疗方法（生物制剂和口服小分子抑制剂/调节剂）时，安全性是一个关键考虑因素。我们进行了一项系统评价和荟萃分析，比较了在活性对照研究中使用高级治疗方法与严重感染风险的关系。
通过系统搜索，我们纳入了 20 项头对头研究，比较了 IBD 患者中肿瘤坏死因子 α（TNFα）拮抗剂、vedolizumab、ustekinumab、tofacitinib、filgotinib 和 ozanimod 治疗严重感染风险。我们进行了随机效应荟萃分析，比较了不同的高级治疗方法。
在所有 IBD 患者中，vedolizumab 与 TNFα 拮抗剂相比，严重感染风险无显著差异（17 个队列：比值比[OR]，0.84；95%可信区间，0.68-1.04），存在中度异质性（I ² = 37%）；亚组分析显示，vedolizumab 可降低溃疡性结肠炎患者严重感染的风险（11 个队列：OR，0.68；95%可信区间，0.56-0.83；I ² = 0%），但在克罗恩病（CD）患者中无此作用（9 个队列：OR，1.03；95%可信区间，0.78-1.35；I ² = 42%）。年龄、性别、既往生物制剂暴露和生物单药治疗并未影响这种关联。在 CD 患者中，ustekinumab 与 TNFα 拮抗剂相比，严重感染风险降低（3 个队列：OR，0.49；95%可信区间，0.25-0.93；I ² = 16%），与 vedolizumab 相比，严重感染风险降低（3 个队列：OR，0.40；95%可信区间，0.17-0.93；I ² = 67%）。少数研究比较了其他高级治疗方法。
在溃疡性结肠炎患者中，vedolizumab 可能比 TNFα 拮抗剂具有净获益，但在 CD 患者中并非如此。在 CD 患者中，ustekinumab 可能比 TNFα 拮抗剂和 vedolizumab 具有净获益。
