title: Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review.
abstract: OBJECTIVE
  To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy.
  
  
  METHODS
  A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers.
  
  
  RESULTS
  Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17-0.39) and 0.49 (95% CI 0.27-0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression.
  
  
  CONCLUSIONS
  Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.
authors.affiliation: From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center. t.kuijper@erasmusmc.nl.
authors.forename: T Martijn
authors.initials: TM
authors.lastname: Kuijper
authors.affiliation: From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center.
authors.forename: Femke B G
authors.initials: FB
authors.lastname: Lamers-Karnebeek
authors.affiliation: From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center.
authors.forename: Johannes W G
authors.initials: JW
authors.lastname: Jacobs
authors.affiliation: From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center.
authors.forename: Johanna M W
authors.initials: JM
authors.lastname: Hazes
authors.affiliation: From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center.
authors.forename: Jolanda J
authors.initials: JJ
authors.lastname: Luime
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy*; D001688:Biological Products / Q000627:therapeutic use*; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D028761:Withholding Treatment
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D000068800:Etanercept; D008727:Methotrexate
keywords: BIOLOGIC DMARD; REMISSION; RHEUMATOID ARTHRITIS; SYNTHETIC DMARD; SYSTEMATIC REVIEW; TREATMENT DEESCALATION