title: Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis.
abstract: OBJECTIVE
  To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations.
  
  
  METHODS
  Medline, Embase and Cochrane databases were searched for articles published between January 2009 and February 2013 on infliximab, etanercept, adalimumab, certolizumab-pegol, golimumab, anakinra, abatacept, rituximab, tocilizumab and biosimilar DMARDs (bsDMARDs) in phase 3 development. Abstracts from 2011 to 2012 American College of Rheumatology (ACR) and 2011-2013 EULAR conferences were obtained.
  
  
  RESULTS
  Fifty-one full papers, and 57 abstracts were identified. The randomised controlled trials (RCT) confirmed the efficacy of bDMARD+conventional synthetic DMARDs (csDMARDs) versus csDMARDs alone (level 1B evidence). There was some additional evidence for the use of bDMARD monotherapy, however bDMARD and MTX combination therapy for all bDMARD classes was more efficacious (1B). Clinical and radiographic responses were high with treat-to-target strategies. Earlier improvement in signs and symptoms were seen with more intensive initial treatment strategies, but outcomes were similar upon addition of bDMARDs in patients with insufficient response to MTX. In general, radiographic progression was lower with bDMARD use, mainly due to initial treatment effects. Although patients may achieve bDMARD- and drug-free remission, maintenance of clinical responses was higher with bDMARD continuation (1B), but bDMARD dose reduction could be applied (1B). There was still no RCT data for bDMARD switching.
  
  
  CONCLUSIONS
  The systematic literature review confirms efficacy of biological DMARDs in RA. It addresses different treatment strategies with the potential for reduction in therapy, particularly with early disease control, and highlights emerging therapies.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, , Leeds, UK.
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Nam
authors.forename: Sofia
authors.initials: S
authors.lastname: Ramiro
authors.forename: Cecile
authors.initials: C
authors.lastname: Gaujoux-Viala
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takase
authors.forename: Mario
authors.initials: M
authors.lastname: Leon-Garcia
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Laure
authors.initials: L
authors.lastname: Gossec
authors.forename: Robert
authors.initials: R
authors.lastname: Landewe
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Maya H
authors.initials: MH
authors.lastname: Buch
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Rheumatoid Arthritis; Treatment