Abstract
BackgroundSustained DMARD-free remission (SDFR) is increasingly achievable. The pathogenesis underlying SDFR development is unknown and patient characteristics at diagnosis poorly explain whether SDFR will be achieved. To increase the understanding, we studied the course of disease activity scores (DAS) over time in relation to SDFR development. Subsequently, we explored whether DAS course could be helpful identifying RA patients likely to achieve SDFR.Methods772 consecutive RA patients, promptly treated with csDMARDs (mostly methotrexate and treat-to-target treatment adjustments), were studied for SDFR development (absence of synovitis, persisting minimally 12 months after DMARD stop). The course of disease activity scores (DAS) was compared between RA patients with and without SDFR development within 7 years, using linear mixed models, stratified for ACPA. The relation between 4-month DAS and the probability of SDFR development was studied with logistic regression. Cumulative incidence of SDFR within DAS categories (< 1.6, 1.6–2.4, 2.4–3.6, ≥ 3.6) at 4 months was visualized using Kaplan-Meier curves.ResultsIn ACPA-negative RA patients, those achieving SDFR showed a remarkably stronger DAS decline within the first 4 months, compared to RA patients without SDFR; − 1.73 units (95%CI, 1.28–2.18) versus − 1.07 units (95%CI, 0.90–1.23) (p < 0.001). In APCA-positive RA patients, such an effect was not observed, yet SDFR prevalence in this group was low. In ACPA-negative RA, DAS decline in the first 4 months and absolute DAS levels at 4 months (DAS4 months) were equally predictive for SDFR development. Incidence of SDFR in ACPA-negative RA patients was high (70.2%) when DAS4 months was < 1.6, whilst SDFR was rare (7.1%) when DAS4 months was ≥ 3.6.ConclusionsIn ACPA-negative RA, an early response to treatment, i.e., a strong DAS decline within the first 4 months, is associated with a higher probability of SDFR development. DAS values at 4 months could be useful for later decisions to stop DMARDs.
Highlights
Sustained DMARD-free remission (SDFR) is increasingly achievable
– This is the first study scoping beyond baseline characteristics to understand sustained DMARD-free remission (SDFR), by exploring the course of disease activity scores (DAS) over time in relation to achieving SDFR
– This study showed that early response to treatment, i.e., significant decrease in DAS within the first 4 months after diagnosis, is associated with achieving SDFR in ACPA-negative Rheumatoid arthritis (RA)
Summary
The pathogenesis underlying SDFR development is unknown and patient characteristics at diagnosis poorly explain whether SDFR will be achieved. We studied the course of disease activity scores (DAS) over time in relation to SDFR development. Tapering and sustained cessation of DMARDS, termed sustained DMARD-free remission (SDFR), is increasingly achievable in ACPA-negative and ACPA-positive RA [2, 3]. Several patient characteristics at time of diagnosis have been studied [2, 7,8,9,10], but these poorly explained SDFR development. Different mechanisms underlying SDFR development might be involved in ACPApositive and ACPA-negative RA patients. It has been suggested that SDFR development in ACPA-negative RA patients solely reflects spontaneous resolution of inflammation in patients misclassified as RA (e.g., reactive arthritis or osteoarthritis). The finding that SDFR has become more frequent with improved treatment strategies, in ACPA-negative RA [2], indicates that SDFR is a real disease outcome in RA patients that otherwise would have had a chronic disease
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