title: Effectiveness of biologic therapies for rheumatoid arthritis: an indirect comparisons approach.
abstract: OBJECTIVE
  To compare the efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) versus placebo with or without methotrexate, in treating rheumatoid arthritis.
  
  
  METHODS
  Comparative effectiveness analysis using an indirect treatment comparison (ITC) method in a Bayesian framework.
  
  
  METHODS
  Adults with rheumatoid arthritis who had been enrolled in randomized controlled trials (RCTs) and had never failed biologic DMARD therapy.
  
  
  RESULTS
  Two random-effects logistic regression models, representing 6 and 12 months of treatment, were created using RCTs identified in a literature search. Twenty-three RCTs (11,589 patients) were included in the 6-month model and 10 RCTs (6051 patients) in the 12-month model. Nine biologic DMARDs in five therapeutic drug classes were included in the 6-month model, and six biologic DMARDs in three classes were included in the 12-month model. Our efficacy end point was the American College of Rheumatology 50% improvement criteria. In the 6-month model, all biologic DMARDs and methotrexate were significantly more efficacious than placebo and ranked in the following order: certolizumab (median log odds ratio [OR] 2.6), tocilizumab (1.7), rituximab (1.6), infliximab (1.6), etanercept (1.4), adalimumab (1.4), golimumab (1.4), abatacept (1.2), anakinra (1.0), and methotrexate (0.8). Of 45 pairwise comparisons, certolizumab was significantly more efficacious than methotrexate, but no other comparisons were significant. The rank order in the 12-month analysis was certolizumab (median log OR 2.0), rituximab (2.0), adalimumab (1.4), infliximab (1.4), etanercept (0.9), abatacept (0.6), and methotrexate (0.8). Of the 21 pairwise comparisons, none were significant. The results of the model using therapeutic class revealed that each class was more efficacious than placebo. In pairwise comparisons, each class was more efficacious than methotrexate, but none was more efficacious than another.
  
  
  CONCLUSIONS
  Use of emerging ITC methods enabled us to compare the efficacy of biologic DMARDs for the treatment of rheumatoid arthritis in the absence of direct head-to-head comparison trials. Our methods enabled us to rank order these treatments. Further analyses by drug and by therapeutic class suggest that biologic DMARDs are similarly efficacious.
authors.affiliation: Pharmaceutical Outcomes Research and Policy Program, Department of Medical Education and Biomedical Informatics, University of Washington, Seattle, Washington 98195-7630, USA. bdevine@uw.edu
authors.forename: Emily Beth
authors.initials: EB
authors.lastname: Devine
authors.forename: Rafael
authors.initials: R
authors.lastname: Alfonso-Cristancho
authors.forename: Sean D
authors.initials: SD
authors.lastname: Sullivan
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D006801:Humans; D015201:Meta-Analysis as Topic; D008727:Methotrexate / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D008727:Methotrexate