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

M. Verstappen, E. Van Mulligen*, P. H.P. De Jong, A. H.M. Van Der Helm-Van Mil

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)
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Objectives Although 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. Methods A 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. Results From 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. Conclusions DFR 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.

Original languageEnglish
Article numbere001220
JournalRMD Open
Issue number1
Publication statusPublished - 10 May 2020

Bibliographical note

Funding Information:
Funding The research leading to these results has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (starting grant, agreement no 714312) and from the Dutch Arthritis Foundation. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Publisher Copyright:
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


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