Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN; USA; Email:
J Gastrointestin Liver Dis. 2013 Sep;22(3):269-76.
BACKGROUND & AIM: Incremental increase in the risk of serious infections with combinations of tumor necrosis factor-alpha (TNF-α) inhibitors and immunomodulators compared to monotherapy with these agents in inflammatory bowel disease (IBD) is unclear. Our aim was to analyze whether there is such an incremental increase in the odds of serious infections.
The FDA Adverse Event Reporting System (2003 - June 2011) was queried for 'Primary Suspect' reports of various infections with TNF-α inhibitors, systemic corticosteroids and immunomodulators with usage indication of IBD. Odds ratios (ORs) were calculated for baseline odds of infections as well as serious infections (requiring hospitalization and/or death) with monotherapy and combination therapy (compared to 5-Aminosalicylates) as well as incremental increase in odds for dual or triple combination therapy (compared to monotherapy or dual combination therapy respectively) using Fisher's exact test with SPSS 20 (IBM Co. Armonk, NY, USA).
TNF-α inhibitor (OR 1.95; CI, 1.06-3.59) and immunomodulator (OR 9.99; CI, 1.28-78.16) monotherapy as well as in combination augmented baseline odds of serious infection for IBD patients. No incremental increase in the odds with combination therapy was seen when an immunomodulator was added to a TNF-α inhibitor (OR 0.37; CI, 0.05-2.80) and when both were used with a systemic corticosteroid (OR 0.91; CI, 0.50-1.66). Variations in these were seen for the individual infection subtypes.
TNF-α inhibitor and immunomodulator monotherapy increase the baseline odds of acquiring a serious infection. Combination therapy with these drugs does not further increase the odds of serious infections compared to monotherapy.
与肿瘤坏死因子-α（TNF-α）抑制剂和免疫调节剂的单药治疗相比，在炎症性肠病（IBD）中这些药物的联合应用会导致严重感染风险的逐渐增加，但目前尚不清楚这种风险是否确实存在。本研究旨在分析是否存在这种严重感染风险的递增。
利用美国食品药品监督管理局（FDA）不良事件报告系统（2003 年-2011 年 6 月），检索 TNF-α抑制剂、全身皮质类固醇和免疫调节剂在治疗 IBD 适应证下的各种感染的“主要嫌疑”报告。采用 SPSS 20（IBM Co.，Armonk，NY，USA）中的 Fisher 确切概率法，计算单药治疗和联合治疗（与 5-氨基水杨酸相比）以及双药或三药联合治疗（与单药或双药联合治疗相比）时基线感染率和严重感染（需要住院和/或死亡）的比值比（OR），以评估严重感染的风险。
TNF-α抑制剂（OR 1.95；95%CI，1.06-3.59）和免疫调节剂（OR 9.99；95%CI，1.28-78.16）单药治疗以及联合应用均增加了 IBD 患者严重感染的基线风险。当免疫调节剂联合 TNF-α抑制剂时（OR 0.37；95%CI，0.05-2.80）或当两者与全身皮质类固醇联合应用时（OR 0.91；95%CI，0.50-1.66），联合治疗并未增加严重感染的风险。对于不同的感染类型，这些结果存在差异。
TNF-α抑制剂和免疫调节剂单药治疗会增加获得严重感染的基线风险。与单药治疗相比，这些药物的联合应用并未进一步增加严重感染的风险。
