Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: a systematic literature review and meta-analysis of randomized controlled trials

Rheumatology (Oxford). 2011 Mar;50(3):552-62. doi: 10.1093/rheumatology/keq343. Epub 2010 Nov 14.


Objective: To assess the risk of adverse events (AEs) in patients with RA treated with tocilizumab, an IL-6 receptor antibody, in published randomized controlled trials (RCTs).

Methods: A systematic literature search was conducted using the Cochrane library, PUBMED and EMBASE for all RCTs (of the use of tocilizumab for RA) until September 2009. Fixed effect meta-analyses were conducted to compare the incidence of AEs after treatment with tocilizumab 8 and 4 mg/kg in combination with MTX, and 8 mg/kg tocilizumab monotherapy, with controls. Pooled summary odds ratios (ORs) were calculated using the Mantel-Haenszel method.

Results: Six trials were analysed (four trials included 8 mg/kg tocilizumab and MTX combination therapy, three of which also assessed the 4 mg/kg dose). Three studies assessed tocilizumab monotherapy at 8 mg/kg. Pooled ORs revealed statistical significance for an increased risk of AEs in the 8 mg/kg combination group compared with controls (OR = 1.53; 95% CI 1.26, 1.86). The risk of infection was significantly higher in the 8 mg/kg combination group compared with controls (OR = 1.30; 95% CI 1.07, 1.58). No increased incidence of malignancy, tuberculosis reactivation or hepatitis was seen.

Conclusion: Tocilizumab in combination with MTX as a treatment for RA is associated with a small but significantly increased risk of AEs, which is comparable with that of other biologics. Vigilance for untoward effects is, therefore, imperative in any patient treated with these immuno-suppressive agents.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • tocilizumab
  • Methotrexate