title: Biologic discontinuation studies: a systematic review of methods.
abstract: OBJECTIVE
  We conducted a systematic review to assess the design and 'failure definition' in studies of biologic discontinuation in rheumatoid arthritis (RA).
  
  
  METHODS
  We found 403 studies on PubMed, and included nine published papers and five abstracts from scientific meetings. We used a structured extraction form to collect information regarding study design and outcome (failure) definition.
  
  
  RESULTS
  Three types of studies were found: randomised controlled trials, long-term extension studies of clinical trials and prospective discontinuation studies. The largest study had 196 subjects in the discontinuation arm. Most studies allowed concomitant use of non-biologic drugs at biologic discontinuation. Heterogeneity was also found in the failure definition. Although all studies used measures of disease activity, the threshold for failure and the time point of assessment differed among studies. Few studies incorporated changing use of non-biologic drugs or glucocorticoids into the failure definition.
  
  
  CONCLUSIONS
  Although many studies have examined the outcome of biologic discontinuation, they have all been relatively small. Typical practice studies from registries may add important information but will likely need to rely on a broader failure definition.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, , Boston, Massachusetts, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yoon-Kyoung
authors.initials: YK
authors.lastname: Sung
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Sang-Cheol
authors.initials: SC
authors.lastname: Bae
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsui
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
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; D006801:Humans; D012074:Remission Induction / Q000379:methods; D012107:Research Design; D009626:Terminology as Topic; D017211:Treatment Failure; D028761:Withholding Treatment
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products
keywords: biologic DMARDs; discontinuation; remission; rheumatoid arthritis