Shah Eric D, Farida Jeremy P, Siegel Corey A, Chong Kelly, Melmed Gil Y
*Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan; †Section of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; ‡Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico; and §Division of Gastroenterology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Inflamm Bowel Dis. 2017 Apr;23(4):570-577. doi: 10.1097/MIB.0000000000001049.
The overall risk for infection with contemporary biological agents in treating Crohn's disease (CD) and ulcerative colitis (UC) has not been systematically assessed.
We performed a PubMed and Cochrane database literature search to evaluate randomized, placebo-controlled trials of biologics in treating UC and CD. Meta-analysis was performed using a DerSimonian and Laird random effects model. We determined relative risk (RR) of harm against placebo; number needed to harm (NNH) was reported when appropriate. Heterogeneity and publication bias were assessed.
Fourteen trials (6 UC and 8 CD) evaluating 5107 patients were included. For anti-tumor necrosis factor agents used in the treatment of UC, golimumab {NNH of 9.3, RR = 1.4 (95% confidence interval [CI], 1.04-1.8)} and pooled studies of infliximab and adalimumab (NNH = 17.2, RR = 1.2 [95% CI, 1.0-1.3]) had a statistically significant higher risk for any infection versus placebo. Risk was not significantly increased in anti-tumor necrosis factor trials in CD (RR = 1.1 [95% CI, 0.8-1.5]). By contrast, anti-integrin agents in UC (RR = 1.0 [95% CI, 0.9-1.2]) or CD (RR = 1.1 [95% CI, 0.97-1.3]) did not confer a statistically significant excess risk of infection versus placebo.
Anti-tumor necrosis factor therapy but not anti-integrin therapy is associated with a greater infection risk than placebo in treating UC. Neither class of therapy is associated with increased infection risk over placebo in treating CD. Our findings can help guide patient-centered discussions regarding the risk for infection with biological agents.
治疗克罗恩病（CD）和溃疡性结肠炎（UC）时使用当代生物制剂感染的总体风险尚未得到系统评估。
我们进行了PubMed和Cochrane数据库文献检索，以评估生物制剂治疗UC和CD的随机、安慰剂对照试验。采用DerSimonian和Laird随机效应模型进行荟萃分析。我们确定了相对于安慰剂的伤害相对风险（RR）；在适当情况下报告伤害所需人数（NNH）。评估了异质性和发表偏倚。
纳入了14项评估5107例患者的试验（6项UC试验和8项CD试验）。对于用于治疗UC的抗肿瘤坏死因子药物，戈利木单抗（NNH为9.3，RR = 1.4[95%置信区间（CI），1.04 - 1.8]）以及英夫利昔单抗和阿达木单抗的汇总研究（NNH = 17.2，RR = 1.2[95%CI，1.0 - 1.3]）与安慰剂相比，任何感染的风险在统计学上显著更高。CD的抗肿瘤坏死因子试验中风险没有显著增加（RR = 1.1[95%CI，0.8 - 1.5]）。相比之下，UC（RR = 1.0[95%CI，0.9 - 1.2]）或CD（RR = 1.1[95%CI，0.97 - 1.3]）中的抗整合素药物与安慰剂相比，感染风险没有统计学上的显著增加。
在治疗UC时，抗肿瘤坏死因子疗法而非抗整合素疗法与比安慰剂更高的感染风险相关。在治疗CD时，这两类疗法与安慰剂相比均未增加感染风险。我们的研究结果有助于指导以患者为中心的关于生物制剂感染风险的讨论。
