title: Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis: A Meta-Epidemiological Study.
abstract: OBJECTIVE
  To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs)) for rheumatoid arthritis (RA).
  
  
  METHODS
  We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR).
  
  
  RESULTS
  Sixty-two trials (19,923 RA patients) were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naïve" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66) and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87), test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (β = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03). Analyses conducted using DAS28-remission as the outcome supported the above-mentioned findings.
  
  
  CONCLUSIONS
  Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naïve and trials including patients with shorter disease durations.
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Anton Wulf
authors.initials: AW
authors.lastname: Christensen
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Tarp
authors.affiliation: David Geffen School of Medicine, University of California in Los Angeles, Los Angeles, California, United States of America.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Døssing
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Kirstine
authors.initials: K
authors.lastname: Amris
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bliddal
authors.affiliation: Kennedy Institute of Rheumatology: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, United Kingdom.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
authors.affiliation: The Parker Institute, Department of Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg, Frederiksberg, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology*; D002986:Clinical Trials as Topic / Q000592:standards*; D016021:Epidemiologic Studies; D006801:Humans; D058990:Molecular Targeted Therapy; D012042:Registries; D012107:Research Design; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents