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

Arthritis Rheum. 2011 Jun;63(6):1479-85. doi: 10.1002/art.30310.

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.

Conclusion: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Communicable Diseases / epidemiology
  • Communicable Diseases / etiology*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasms / chemically induced*
  • Neoplasms / epidemiology
  • Randomized Controlled Trials as Topic
  • Risk
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antirheumatic Agents
  • Tumor Necrosis Factor-alpha
  • Methotrexate