DMARD-free remission as novel treatment target in rheumatoid arthritis: A systematic literature review of achievability and sustainability

• Published in: Rheumatic & musculoskeletal diseases open 2020-05, Vol.6 (1), p.e001220
• Main Authors: Verstappen, M, van Mulligen, E, de Jong, P H P, van der Helm-Van Mil, A H M
• Format: Article
• Language: English
• Subjects: Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Clinical trials; Clinical Trials as Topic; disease flare; DMARD-free remission; Drug Administration Schedule; Humans; Induction Chemotherapy - methods; Literature reviews; Observational Studies as Topic; Quality; Rheumatoid Arthritis; Severity of Illness Index; Studies; Sustainability; Symptom Flare Up; Systematic review; tapering; Time Factors; Treatment Outcome; Withholding Treatment
• ISSN: 2056-5933; 2056-5933
• DOI: 10.1136/rmdopen-2020-001220

ObjectivesAlthough current treatment guidelines for rheumatoid arthritis (RA) suggest tapering disease-modifying anti-rheumatic drugs (DMARDs), it is unclear whether DMARD-free remission (DFR) is an achievable and sustainable outcome. Therefore, we systematically reviewed the literature to determine the prevalence and sustainability of DFR and evaluated potential predictors for DFR.MethodsA systematic literature search was performed in March 2019 in multiple databases. All clinical trials and observational studies reporting on discontinuation of DMARDs in RA patients in remission were included. Our quality assessment included a general assessment and assessment of the description of DFR. Prevalence of DFR and its sustainability and flares during tapering and after DMARD stop were summarised. Also, potential predictors for achieving DFR were reviewed.ResultsFrom 631 articles, 51 were included, comprising 14 clinical trials and 5 observational studies. DFR definition differed, especially for the duration of DMARD-free state. Considering only high- and moderate-quality studies, DFR was achieved in 5.0%–24.3% and sustained DFR (duration>12 months) in 11.6%–19.4% (both relative to the number of patients eligible for tapering). Flares occurred frequently during DMARD tapering (41.8%–75.0%) and in the first year after achieving DFR (10.4%–11.8%), while late flares, >1 year after DMARD-stop, were infrequent (0.3%–3.5%). Many patient characteristics lacked association with DFR. Absence of autoantibodies and shared epitope alleles increased the chance of achieving DFR.ConclusionsDFR is achievable in RA and is sustainable in ~10%–20% of patients. DFR can become an important outcome measure for clinical trials and requires consistency in the definition. Considering the high rate of flares in the first year after DMARD stop, a DMARD-free follow-up of >12 months is advisable to evaluate sustainability.