• Debbie M Boeters, Leonie E Burgers, Eric H Sasso, HuizingaTom W JTWJDepartment of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands., and van der Helm-van MilAnnette H MAHMDepartment of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands.Department of Rheumatology, Erasmus University Medical Center, Rotterdam, the Netherlands..
• Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, the Netherlands. D.M.Boeters@lumc.nl.
• Arthritis Res. Ther. 2019 May 14; 21 (1): 121.

BackgroundDisease-modifying antirheumatic drug (DMARD)-free remission, the sustained absence of synovitis after DMARD cessation, is increasingly achievable, especially in autoantibody-negative rheumatoid arthritis (RA). However, underlying mechanisms are unknown and patient subgroups that achieve this outcome are insufficiently characterized. We evaluated whether serological biomarkers at disease onset, as measured within the multi-biomarker disease activity (MBDA) score, are differently expressed in RA patients who achieve sustained DMARD-free remission.MethodsTwo hundred ninety-nine RA patients were evaluated for achievement of sustained DMARD-free remission during a median follow-up of 4.3 years. Twelve biomarkers, as included in the MBDA score, were determined from the serum obtained at disease onset. Patients were categorized as having a low (< 30), moderate (30-44) or high (> 44) score. Analyses were stratified for anti-citrullinated protein antibodies (ACPA) based under the assumption that ACPA-positive and ACPA-negative RA are different disease entities.ResultsTwenty percent achieved sustained DMARD-free remission. Overall, high MBDA scores were associated with achieving DMARD-free remission (high vs. low HR 3.8, 95% CI 1.2-12.2). Among ACPA-negative RA patients, moderate or high scores associated strongly with DMARD-free remission (moderate vs. low HR 9.4, 95% CI 1.2-72.9; high vs. low HR 9.7, 95% CI 1.3-71.1). This association was independent of age and other clinical factors (high vs. low HR 8.2, 95% CI 1.1-61.8). For ACPA-negative RA patients, the biomarkers C-reactive protein, serum amyloid A and matrix metalloproteinase-3 were individually associated with sustained DMARD-free remission. Among ACPA-positive RA patients, scores were not associated with DMARD-free remission.ConclusionsACPA-negative RA patients who achieved sustained DMARD-free remission after treatment withdrawal were characterized by moderate to high MBDA scores at diagnosis. This is the first evidence that ACPA-negative RA can be subdivided in clinically relevant subsets at disease onset using a protein profile.

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