title: Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 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 (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations.
  
  
  METHODS
  MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained.
  
  
  RESULTS
  The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or 'spacing' was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B).
  
  
  CONCLUSIONS
  This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.|NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Jackie L
authors.initials: JL
authors.lastname: Nam
authors.affiliation: Center for Rheumatic Diseases, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takase-Minegishi
authors.affiliation: .
authors.forename: Sofia
authors.identifier: http://orcid.org/0000-0002-8899-9087
authors.initials: S
authors.lastname: Ramiro
authors.affiliation: Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), The Karolinska Institute, Stokholm, Sweden.
authors.forename: Katerina
authors.initials: K
authors.lastname: Chatzidionysiou
authors.affiliation: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.|Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: .
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Department of Rheumatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Bijlsma
authors.affiliation: Department of Rheumatology, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Rheumatology, Paris Descartes University, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, INSERM (U1153): Clinical Epidemiology and Biostatistics, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands.|EULAR Standing Committee of People with Arthritis/Rheumatism in Europe.
authors.forename: Marieke
authors.initials: M
authors.lastname: Scholte-Voshaar
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands.|Department of Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: van Vollenhoven
authors.affiliation: Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology Center, Amsterdam, The Netherlands.|Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
mesh_terms: D026683:Advisory Committees; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001688:Biological Products / Q000008:administration & dosage / Q000627:therapeutic use*; D059451:Biosimilar Pharmaceuticals / Q000627:therapeutic use; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D006801:Humans; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D059451:Biosimilar Pharmaceuticals; D014409:Tumor Necrosis Factor-alpha
keywords: Anti-TNF; DMARDs (biologic); Rheumatoid Arthritis