title: bDMARD Dose Reduction in Rheumatoid Arthritis: A Narrative Review with Systematic Literature Search.
abstract: BACKGROUND
  Although bDMARDs are effective in the treatment of RA, they are associated with dose-dependent side effects, patient burden, and high costs. Recently, many studies have investigated the possibility of discontinuing or tapering bDMARDs when patients have reached their treatment goal. The aim of this review is to provide a narrative overview of the existing evidence on bDMARD dose reduction and to provide answers to specific dose-reduction-related questions that are of interest to clinicians.
  
  
  METHODS
  We systematically searched for relevant studies in four scientific databases. Furthermore, we screened the references of reviews and relevant studies.
  
  
  RESULTS
  Our searches resulted in 45 original studies of bDMARD dose reduction in RA patients (15 RCTs and 30 observational studies). Current evidence shows that bDMARD dose reduction can be considered in all RA patients who achieve stable (e.g., ≥6 months) low disease activity or remission. The best strategies seem to be disease-activity-guided dose optimization and fixed dose reduction, since direct bDMARD discontinuation (without restarting) results in a high flare rate, worse physical functioning, and more joint damage. When tapering the bDMARD treatment of a patient, disease activity should be monitored closely, and if a flare occurs, the dose should be increased to the lowest effective dose. Current evidence shows that restarting bDMARD treatment is effective and safe. Unfortunately, no clear predictors of successful dose reduction have been identified so far.
  
  
  CONCLUSIONS
  The current evidence and rising healthcare costs urge that dose reduction should be considered for eligible patients. However, the decision to start dose reduction should be made in shared decision-making. Future research should focus not only on a better understanding of the effects of dose reduction on clinical outcomes but also on the perspectives of patients and physicians as well as the implementation of this new treatment principle.
authors.affiliation: Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands. L.Verhoef@maartenskliniek.nl.
authors.forename: Lise M
authors.initials: LM
authors.lastname: Verhoef
authors.affiliation: Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands.
authors.forename: Lieke
authors.initials: L
authors.lastname: Tweehuysen
authors.affiliation: IQ Healthcare, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Hulscher
authors.affiliation: Pierre et Marie Curie University-Paris 6, Sorbonne Universités, GRC-08 (EEMOIS), Paris, France.|Rheumatology Department, AP-HP, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Fautrel
authors.affiliation: Department of Rheumatology, Sint Maartenskliniek, Nijmegen, The Netherlands.|Department of Rheumatology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Alfons A
authors.initials: AA
authors.lastname: den Broeder
keywords: Discontinuation; Dose de-escalation; Dose reduction; Dose titration; Drug holiday; Rheumatoid arthritis; Spacing; Tapering; Treatment relaxation; bDMARDs