BACKGROUND & AIMS We performed a systematic review and meta-analysis to evaluate the comparative risk of serious infections with tumor necrosis factor (TNF) antagonists, non-TNF targeted biologics, tofacitinib, and immunosuppressive agents in patients with inflammatory bowel diseases (IBDs). METHODS In a systematic search of publications, through March 18, 2018, we identified 15 observational studies (>500 person-years) of patients with IBD treated with TNF antagonists, non-TNF targeted biologics, tofacitinib, and/or immunosuppressive agents (thiopurines, methotrexate) that reported risk of serious infections. Only studies with active comparators were included, to allow appropriate comparative synthesis. We performed random-effects meta-analysis and estimated relative risk (RR) and 95% CIs. RESULTS Compared with anti-TNF monotherapy, risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in 6 cohorts: RR, 1.19; 95% CI, 1.03-1.37), with anti-TNF and a corticosteroid (in 4 cohorts: RR, 1.64; 95% CI, 1.33-2.03), or with all 3 drugs (in 2 cohorts: RR, 1.35; 95% CI, 1.04-1.77); there was minimal heterogeneity among studies. In contrast, monotherapy with an immunosuppressive agent was associated with a lower risk of serious infections than monotherapy with a TNF antagonist (7 cohorts: RR, 0.61; 95% CI 0.44-0.84) or a TNF antagonist with an immunosuppressive agent (2 cohorts: RR, 0.56; 95% CI, 0.39-0.81). Infliximab-based therapy was associated with a lower risk of serious infections compared with adalimumab-based therapy in patients with ulcerative colitis (4 cohorts: RR, 0.57; 95% CI, 0.33-0.97), but not Crohn's disease (4 cohorts: RR, 0.91; 95% CI, 0.49-1.70). Few data were available on the comparative safety of biologic agents that do not inhibit TNF and tofacitinib. CONCLUSIONS Combination therapies for IBD that include TNF antagonists, especially with corticosteroids, are associated with a higher risk of serious infection, whereas monotherapy with an immunosuppressive agent is associated with a lower risk, compared with monotherapy with a TNF antagonist. Studies are needed to evaluate the comparative safety of non-TNF targeted biologics and small molecules for treatment of IBD.

中文翻译：

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生物和/或免疫抑制疗法对炎症性肠病患者发生严重感染的比较风险：系统评价和荟萃分析。

背景与目的我们进行了系统的综述和荟萃分析，以评估炎症性肠病（IBD）患者中肿瘤坏死因子（TNF）拮抗剂，非TNF靶向生物制剂，托法替尼和免疫抑制剂严重感染的相对风险。方法在2018年3月18日之前对出版物进行系统搜索的过程中，我们确定了15项IBD患者的观察性研究（> 500人年），这些患者接受TNF拮抗剂，非TNF靶向生物制剂，托法替尼和/或免疫抑制剂（硫代嘌呤）治疗（甲氨蝶呤）报告有严重感染的风险。仅包括具有活性比较剂的研究，以进行适当的比较合成。我们进行了随机效应荟萃分析，并估计了相对风险（RR）和95％的置信区间。结果与抗TNF单药治疗相比，抗TNF和免疫抑制剂（6组：RR，1.19； 95％CI，1.03-1.37），抗TNF和皮质类固醇（4组：RR，1.64； 6组：RR，1.63； 1.3）增加了严重感染的风险。 95％CI，1.33-2.03），或同时使用所有3种药物（2组：RR，1.35； 95％CI，1.04-1.77）；研究之间的异质性最小。相比之下，与TNF拮抗剂（7组：RR，0.61； 95％CI 0.44-0.84）或TNF拮抗剂与免疫抑制剂（2组：相对危险度（RR）0.56； 95％CI（0.39-0.81）。与基于阿达木单抗的治疗相比，基于英夫利昔单抗的治疗与溃疡性结肠炎患者的严重感染风险相比较低（4组：RR，0.57； 95％CI，0.33-0.97），但与克罗恩病无关（4组：相对危险度，0.91；95％CI，0.49-1.70）。关于不抑制TNF和tofacitinib的生物制剂的相对安全性的数据很少。结论包括TNF拮抗剂（尤其是皮质类固醇激素）的IBD联合疗法与严重感染的风险较高，而与TNF拮抗剂的单一疗法相比，免疫抑制剂的单药治疗风险较低。需要进行研究以评估非TNF靶向生物制剂和小分子治疗IBD的比较安全性。与使用TNF拮抗剂的单一疗法相比，与TNF拮抗剂的单一疗法相比，与TNF拮抗剂的单一疗法相比，与严重感染的更高风险相关，而与免疫抑制剂的单一疗法相关的风险较低。需要进行研究以评估非TNF靶向生物制剂和小分子治疗IBD的比较安全性。与使用TNF拮抗剂的单一疗法相比，与TNF拮抗剂的单一疗法相比，与TNF拮抗剂的单一疗法相比，与严重感染的更高风险相关，而与免疫抑制剂的单一疗法相关的风险较低。需要进行研究以评估非TNF靶向生物制剂和小分子治疗IBD的比较安全性。