比较生物制剂和/或免疫抑制剂治疗炎症性肠病患者严重感染风险的系统评价和荟萃分析。
Comparative Risk of Serious Infections With Biologic and/or Immunosuppressive Therapy in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
机构信息
Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California.
Gastroenterology Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy.
出版信息
Clin Gastroenterol Hepatol. 2020 Jan;18(1):69-81.e3. doi: 10.1016/j.cgh.2019.02.044. Epub 2019 Mar 12.
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.
背景与目的
我们进行了一项系统评价和荟萃分析，以评估肿瘤坏死因子（TNF）拮抗剂、非 TNF 靶向生物制剂、托法替尼和免疫抑制剂在炎症性肠病（IBD）患者中的严重感染风险。
方法
通过系统检索出版物，截至 2018 年 3 月 18 日，我们确定了 15 项观察性研究（>500 人年），这些研究评估了接受 TNF 拮抗剂、非 TNF 靶向生物制剂、托法替尼和/或免疫抑制剂（硫唑嘌呤、甲氨蝶呤）治疗的 IBD 患者的严重感染风险。仅纳入了有活性对照的研究，以便进行适当的比较综合。我们进行了随机效应荟萃分析，并估计了相对风险（RR）和 95%置信区间（CI）。
结果
与抗 TNF 单药治疗相比，TNF 联合免疫抑制剂（6 项队列：RR，1.19；95%CI，1.03-1.37）、TNF 联合皮质类固醇（4 项队列：RR，1.64；95%CI，1.33-2.03）或 3 种药物联合治疗（2 项队列：RR，1.35；95%CI，1.04-1.77）的严重感染风险增加；各研究之间的异质性很小。相反，与 TNF 拮抗剂单药治疗或 TNF 拮抗剂联合免疫抑制剂相比，免疫抑制剂单药治疗与严重感染风险降低相关（7 项队列：RR，0.61；95%CI，0.44-0.84；2 项队列：RR，0.56；95%CI，0.39-0.81）。与阿达木单抗相比，英夫利昔单抗治疗溃疡性结肠炎患者的严重感染风险较低（4 项队列：RR，0.57；95%CI，0.33-0.97），但克罗恩病患者无此相关性（4 项队列：RR，0.91；95%CI，0.49-1.70）。关于不抑制 TNF 的生物制剂和托法替尼的比较安全性的数据很少。
结论
IBD 的联合治疗方案包括 TNF 拮抗剂，尤其是联合皮质类固醇，与严重感染风险增加相关，而免疫抑制剂单药治疗与 TNF 拮抗剂单药治疗相比，严重感染风险降低。需要研究来评估非 TNF 靶向生物制剂和小分子治疗 IBD 的比较安全性。
Zotero 插件