Background:Current treatment guidelines for rheumatoid arthritis (RA) suggest tapering DMARDs.1Discontinuation of DMARD-treatment is of increasing interest, and DMARD-free remission (DFR) is regarded an important future outcome.2 3However, lack of knowledge on DFR prevalence, its sustainability, and the characteristics of patients achieving DFR currently hampers the use of DFR as primary outcome.Objectives:To increase the understanding of DFR in RA, and to support studies aiming to include this as primary outcome, we systematically reviewed the literature to determine prevalence and sustainability of DFR. Potential predictors of DFR were evaluated to increase insight in patient characteristics favourable for achieving this outcome.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, flares during tapering and after DMARD-stop were summarized. Also, potential predictors of 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%. Flares occurred frequently during DMARD-tapering (41.8%-75.0%) and in the first year after achieving DFR (10.4%-11.8%), whilst late flares, >1 year after DMARD-stop, were infrequent (0.3%-3.5%). Many patient characteristics lacked association with DFR. Absence of auto-antibodies and shared epitope alleles increased the risk of achieving DFR.Conclusion:DFR is achievable in RA, and is sustainable in ~10%-20% of patients.1DFR 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.References:[1] Smolen JS, Landewe R, Bijlsma Jea. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.Ann Rheum Dis2017;76(6):960-77. doi: annrheumdis-2016-210715 [pii];10.1136/annrheumdis-2016-210715 [doi][2] Ajeganova S, van Steenbergen HW, van Nies JA, et al. Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms.Ann Rheum Dis2016;75(5):867-73. doi: annrheumdis-2014-207080 [pii];10.1136/annrheumdis-2014-207080 [doi][3] Stamm TA, Machold KP, Aletaha D, et al. Induction of sustained remission in early inflammatory arthritis with the combination of infliximab plus methotrexate: the DINORA trial.Arthritis Res Ther2018;20(1):174. doi: 10.1186/s13075-018-1667-z [doi];10.1186/s13075-018-1667-z [pii]Acknowledgments:We would like to thank J. Schoones, librarian of Leiden University Medical Center, for constructing and carrying out the literature search.Disclosure of Interests:None declared
Adverse events of special interest in clinical trials of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and psoriasis with 37 066 patient-years of tofacitinib exposure
