title: Defining the optimal biological monotherapy in rheumatoid arthritis: A systematic review and meta-analysis of randomised trials.
abstract: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy.
  
  
  
  We searched MEDLINE, EMBASE, CENTRAL, and other sources for randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct and indirect comparisons of the treatment effects, while preserving the randomised comparisons within each trial. PROSPERO identifier: CRD42012002800.
  
  
  
  The analysis comprises 28 trials (8602 patients), including all nine biological agents approved for RA. Eight trials included "DMARD-naïve", and 20 "DMARD-Inadequate responder" (DMARD-IR) patients. All agents except anakinra and infliximab were superior (p < 0.05) to placebo (i.e., no DMARD treatment) with regard to ACR50. Etanercept and rituximab were superior to anakinra (p = 0.018 and p = 0.049, respectively). Tocilizumab was superior to adalimumab (p = 0.0082), anakinra (p = 0.0083), certolizumab (p = 0.037), and golimumab (p = 0.049). No differences among etanercept, tocilizumab, and rituximab were found (p > 0.52). However, because rituximab was evaluated in just 40 patients, our confidence in the estimates is limited. When including only DMARD-IR trials, the same statistical pattern emerged; in addition etanercept and tocilizumab were superior to abatacept. At recommended doses, both etanercept and tocilizumab were superior to adalimumab and certolizumab. No statistically significant differences among biological agents were found with respect to discontinuation due to adverse events (p > 0.068).
  
  
  
  Evidence from randomised trials suggests that most biological agents are effective as monotherapy. Although our confidence in the estimates is limited, etanercept or tocilizumab may be the optimal choice for most patients who need treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.
authors: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark. Electronic address: simon.tarp@regionh.dk.
authors: Simon
authors: S
authors: Tarp
authors: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA.
authors: Daniel E
authors: DE
authors: Furst
authors: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
authors: Anna
authors: A
authors: Dossing
authors: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors: Mikkel
authors: M
authors: Østergaard
authors: Department of Rheumatology, Diagnostic Centre, Silkeborg Regional Hospital, Copenhagen, Denmark.
authors: Tove
authors: T
authors: Lorenzen
authors: ReumaKlinik Roskilde, Roskilde, Denmark; Gildhøj Privathospital, Brøndby, Denmark.
authors: Michael S
authors: MS
authors: Hansen
authors: Medicine Service and Center for Surgical Medical Acute care Research and Transitions, VA Medical Center, Birmingham, AL; Department of Medicine at School of Medicine, Division of Epidemiology at School of Public Health, University of Alabama, Birmingham, AL; Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester, MN.
authors: Jasvinder A
authors: JA
authors: Singh
authors: Section of Rheumatology, Arthritis Research UK and Health and Care Research Wales CREATE Centre, Cardiff University School of Medicine, Cardiff, UK.
authors: Ernest H
authors: EH
authors: Choy
authors: Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands; Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, The Netherlands.
authors: Maarten
authors: M
authors: Boers
authors: Section of Rheumatology and Clinical Immunology, University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Maria E
authors: ME
authors: Suarez-Almazor
authors: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
authors: Lars E
authors: LE
authors: Kristensen
authors: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
authors: Henning
authors: H
authors: Bliddal
authors: Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg og Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.
authors: Robin
authors: R
authors: Christensen
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products
keywords: Biological agents; Meta-analysis; Rheumatoid arthritis; Systematic review