title: Opportunistic infections with anti-tumor necrosis factor-α therapy in inflammatory bowel disease: meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Leeds Gastroenterology Institute, Leeds General Infirmary, Leeds, UK. alexf12399@yahoo.com
authors: Alexander C
authors: AC
authors: Ford
authors: Laurent
authors: L
authors: Peyrin-Biroulet
mesh_terms: D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D009894:Opportunistic Infections / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha