title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Clinical School, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Campbell
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Shweta S
authors.initials: SS
authors.lastname: Bhagat
authors.forename: Richard A
authors.initials: RA
authors.lastname: Parker
authors.forename: Andrew J K
authors.initials: AJ
authors.lastname: Östör
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate