title: The Challenge of Treating Early-Stage Rheumatoid Arthritis: The Contribution of Mixed Treatment Comparison to Choosing Appropriate Biologic Agents.
abstract: BACKGROUND
  Use of biologic drugs is approved for treatment in rheumatoid arthritis (RA), both in established disease and at the early stage of RA (ERA). Identification of ERA and an early therapeutic strategy would lead to greater clinical improvement. Only a few indirect comparisons of the efficacy of different biologic agents in established RA have been performed and, to date, no studies reporting direct comparisons have been performed in ERA.
  
  
  OBJECTIVE
  The aim of this study was to compare, by use of a mixed treatment comparison (MTC), the efficacy profiles of biologic agents in ERA.
  
  
  METHODS
  An extensive literature search was performed to identify results of randomized, controlled trials (RCTs) evaluating biologic agents at licensed doses to treat patients affected by ERA. The primary end points for the analysis were the American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 responses from baseline to various times of follow-up. WinBUGS 1.4 software (MRC Biostatistics Unit, Cambridge, UK) was used to perform the analyses. The MTC results are reported as the relative risk of a response for every single treatment coadministered with methotrexate, versus methotrexate plus placebo, which was used as a comparator in all RCTs.
  
  
  RESULTS
  Ten scientific papers met the study inclusion criteria and were included in the analysis. Data on the use of infliximab, adalimumab, etanercept, abatacept, golimumab, and rituximab were included. No studies reported on the use of certolizumab pegol or tocilizumab in ERA. All biologic agents coadministered with methotrexate proved to be more efficacious than methotrexate plus placebo in inducing ACR20, ACR50, and ACR70 responses. The biologic agent characterized by the highest probability of inducing an ACR70 response was adalimumab (33.28%). Etanercept was the biologic agent with the highest probability of inducing ACR20 and ACR50 responses, in comparison with all other biologic agents, with probability rates of 62.95 and 37.1%, respectively.
  
  
  CONCLUSIONS
  In our analysis, adalimumab proved to be the biologic agent with the highest probability of inducing an ACR70 response in patients affected by ERA, while etanercept was the biologic agent with the highest probability of inducing ACR50 and ACR20 responses.
authors.affiliation: Rheumatology Department, San Pietro Fatebenefratelli Hospital, via Cassia 600, 00189, Rome, Italy.|International Society For Pharmacoeconomics and Outcomes Research (ISPOR), Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Migliore
authors.affiliation: Rheumatology Department, San Pietro Fatebenefratelli Hospital, via Cassia 600, 00189, Rome, Italy. bizzi.emanuele@gmail.com.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bizzi
authors.affiliation: Methods and Models for Economics, Territory and Finance (MEMOTEF) Department, Sapienza University of Rome, Rome, Italy.
authors.forename: Lea
authors.initials: L
authors.lastname: Petrella
authors.affiliation: Internal Medicine and Gastroenterology Department, Nuovo Regina Margherita Hospital, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bruzzese
authors.affiliation: Internal Medicine Department, San Pietro Fatebenefratelli Hospital, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cassol
authors.affiliation: Integrated Solutions Health Economics and Organization (ISHEO), Rome, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Integlia
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001685:Biological Factors / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001685:Biological Factors