Opportunistic Infections With Anti-Tumor Necrosis Factor-α Therapy in Inflammatory Bowel Disease: Meta-Analysis of Randomized Controlled Trials
- 1 August 2013
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in The American Journal of Gastroenterology
- Vol. 108 (8), 1268-1276
- https://doi.org/10.1038/ajg.2013.138
Abstract
Several anti-tumor necrosis factor-α (TNFα) antibodies have demonstrated efficacy in Crohn's disease (CD) and ulcerative colitis (UC). These drugs carry the theoretical risk of opportunistic infection, but no systematic review and meta-analysis has examined this issue specifically. MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to November 2012). Randomized controlled trials (RCTs) recruiting adults with active or quiescent CD or UC comparing anti-TNFα therapy with placebo were eligible. Dichotomous data were pooled to obtain a relative risk (RR) of opportunistic infection, with a 95% confidence interval (CI). The number needed to harm (NNH) was estimated from the reciprocal of the risk difference from the meta-analysis. The search strategy identified 20,563 citations, 21 of which were eligible, reporting 22 separate RCTs with between 2 and 56 weeks of follow-up. In total, there were 39 (0.9%) opportunistic infections among 4,135 patients allocated to anti-TNFα therapy, compared with 9 (0.3%) among 2,919 assigned to placebo. Among patients receiving active therapy these included eight cases of Mycobacterium tuberculosis, eight cases of herpes simplex infection, six cases of oral or esophageal candidiasis, six cases of herpes zoster infection, two cases of varicella-zoster virus infection, two cases of cytomegalovirus or Epstein–Barr virus infection, and one case of Nocardia infection. The RR of developing an opportunistic infection was significantly higher with anti-TNFα therapy (2.05; 95% CI 1.10–3.85, NNH=500; 95% CI 200–1,567). The RR of tuberculosis infection was 2.52 (95% CI 0.62–10.21). Anti-TNF therapy doubles the risk of opportunistic infections in inflammatory bowel disease patients. This underlines the importance of adherence to guidelines for their prevention and management.This publication has 50 references indexed in Scilit:
- Serious Infection and Mortality in Patients With Crohn's Disease: More Than 5 Years of Follow-Up in the TREAT™ RegistryThe American Journal of Gastroenterology, 2012
- A Pooled Analysis of Infections, Malignancy, and Mortality in Infliximab- and Immunomodulator-Treated Adult Patients With Inflammatory Bowel DiseaseThe American Journal of Gastroenterology, 2012
- Adalimumab Induces and Maintains Clinical Remission in Patients With Moderate-to-Severe Ulcerative ColitisGastroenterology, 2012
- Infliximab, Azathioprine, or Combination Therapy for Crohn's DiseaseThe New England Journal of Medicine, 2010
- A Randomized, Double-Blind, Sham-Controlled Study of Granulocyte/Monocyte Apheresis for Active Ulcerative ColitisGastroenterology, 2008
- Tumor necrosis factor-alpha antibody for maintenance of remission in Crohn's diseaseCochrane Database of Systematic Reviews, 2008
- Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trialGut, 2007
- Measuring inconsistency in meta-analysesBMJ, 2003
- Infliximab for the Treatment of Fistulas in Patients with Crohn's DiseaseThe New England Journal of Medicine, 1999
- Meta-analysis in clinical trialsControlled Clinical Trials, 1986