title: Tumor necrosis factor therapy and the risk of serious infection and malignancy in patients with early rheumatoid arthritis: a meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To conduct a meta-analysis of the rates of serious infection and malignancy in patients with early rheumatoid arthritis (RA) who have started anti-tumor necrosis factor (anti-TNF) therapy and had not received treatment with disease-modifying antirheumatic drugs (DMARDs) or methotrexate (MTX).
  
  
  METHODS
  A systematic literature search was conducted through the summer of 2009. All studies included were randomized, double-blind, placebo-controlled trials involving patients with early RA who were started on anti-TNF therapy without prior DMARD/MTX use. Six trials met the inclusion criteria for the meta-analysis, comprising a total of 2,183 patients receiving biologic therapy and 1,236 patients receiving MTX. The data extracted were from published trials.
  
  
  RESULTS
  A pooled odds ratio (OR) (determined using Mantel-Haenszel methods, with a continuity correction designed for sparse data) was calculated for serious infections (requiring hospitalization) and malignancies, comparing anti-TNF therapy to MTX control. The pooled OR for serious infections was 1.28 (95% confidence interval [95% CI] 0.82-2.00) and that for malignancies was 1.08 (95% CI 0.50-2.32). There was no significant difference in either the rate of serious infections or the rate of malignancies between the anti-TNF therapy group and the control group.
  
  
  CONCLUSIONS
  Whereas other meta-analyses have shown an increased risk of serious infection and malignancy in patients receiving anti-TNF therapy, the results of the present meta-analysis show that there is not an increased risk when the patients have early disease and have not previously been treated with DMARDs and/or MTX.
authors.affiliation: University of Western Ontario and St. Joseph's Health Care, London, Ontario, Canada. andy.thompson@sjhc.london.on.ca
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Thompson
authors.forename: Scott W
authors.initials: SW
authors.lastname: Rieder
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D003141:Communicable Diseases / Q000453:epidemiology / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate