title: Tocilizumab in rheumatoid arthritis: a meta-analysis of efficacy and selected clinical conundrums.
abstract: BACKGROUND
  Tocilizumab (TCZ) is a biological agent used for the treatment of moderate to severe rheumatoid arthritis (RA). In the present systematic literature review and meta-analysis, we provide an update on the efficacy and safety of TCZ and our clinical comments for the treatment of RA.
  
  
  METHODS
  We searched PubMed for randomized, double-blind, placebo-controlled clinical trials investigating the effects of TCZ on RA. The initial search included articles from 1966 to December 2011. The search was subsequently updated in April 2013. Studies had to report clinical efficacy using American College of Rheumatology (ACR) 20, 50, and 70 disease measures. The studies included participants who were 18 years of age and who met the ACR 1987 revised criteria for RA for 6 months or longer. Two reviewers independently abstracted the data, and disagreement was resolved by discussion with a third reviewer. Outcome measures were analyzed as odds ratio using the Mantel-Haenszel estimator under a random effects model to account for heterogeneity in intervention effects between trials. Descriptive statistics were used to compare adverse events.
  
  
  RESULTS
  After reviewing and culling, 8 randomized, controlled, double-blind studies were included in the efficacy meta-analysis. TCZ 8mg/kg was statistically favored over TCZ 4mg/kg or placebo regarding ACR responses. Clinically significant adverse events that occurred with TCZ treatment included infections, lipid and liver function test abnormalities, and gastrointestinal side effects, all of which were more common with TCZ.
  
  
  CONCLUSIONS
  This meta-analysis supports the use of TCZ as an appropriate treatment for moderate to severe RA as monotherapy and combination therapy. Close monitoring for significant adverse events is required when treating patients with TCZ. Future long-term trials should focus further on safety of this agent.
authors.affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Navarro
authors.affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA.
authors.forename: Sara
authors.initials: S
authors.lastname: Taroumian
authors.affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA.
authors.forename: Nashla
authors.initials: N
authors.lastname: Barroso
authors.affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA.
authors.forename: Lewei
authors.initials: L
authors.lastname: Duan
authors.affiliation: UCLA David Geffen School of Medicine, Division of Rheumatology, Los Angeles, CA. Electronic address: defurst@mednet.ucla.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Furst
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: Adverse events; Efficacy; Expert opinion; Meta-analysis; Rheumatoid arthritis; Side effects; Tocilizumab; Toxicity