Abstract
BackgroundAlthough infrequent, some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission. The absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA), is known to be associated with this outcome but further mechanisms underlying the chronic nature of RA are largely unknown. Magnetic resonance imaging (MRI)-detected bone marrow edema (BME), or osteitis, strongly predicts erosive progression and is associated with ACPA positivity. Therefore, we hypothesized that the presence of MRI-detected osteitis is also predictive of not achieving DMARD-free sustained remission and that the presence of osteitis mediates the association between ACPA and DMARD-free sustained remission.MethodsA 1.5 T unilateral hand and foot MRI was performed at disease presentation in 238 RA patients, evaluating BME, synovitis, and tenosynovitis (summed as MRI inflammation score). DMARD-free sustained remission, defined as the absence of clinical synovitis after DMARD cessation that persisted during the total follow-up, was assessed (median follow-up 3.8 years). Associations between the different MRI-detected inflammatory features and this outcome were studied. A mediation analysis was performed to study whether the presence of BME mediated the association between ACPA and DMARD-free sustained remission. Finally, patterns of MRI-detected inflammation with regard to DMARD-free sustained remission were studied using partial least squares (PLS) regression.ResultsForty-six (19.3%) patients achieved DMARD-free sustained remission. ACPA positivity associated independently with remission (hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.06–0.39). In contrast, no associations were observed between MRI-detected BME (HR 0.99, 95% CI 0.94–1.03), or other MRI inflammatory features, and achieving DMARD-free sustained remission. Thus, the presence of BME did not mediate the association between ACPA and DMARD-free sustained remission. Furthermore, a PLS analysis revealed that patients who did or did not achieve remission could not be distinguished by patterns of MRI-detected inflammation.ConclusionsAt disease presentation, osteitis, as well as other MRI-detected inflammatory features, was not associated with achieving DMARD-free sustained remission over time. Thus, imaging predictors for joint damage and disease persistence differ. The processes mediating RA chronicity remain largely unsolved.
Highlights
Infrequent, some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission
As joint damage is becoming less prevalent in patients with rheumatoid arthritis (RA), the focus is shifting to other disease outcomes such as disease-modifying antirheumatic drug (DMARD)-free sustained remission [1]
Thirty-seven patients were excluded (22 because they never received DMARD therapy despite fulfilling classification criteria, 4 because the Magnetic resonance imaging (MRI) was performed without contrast, and 11 because of participation in a trial with initial biologic therapy that differed from routine care) [19, 20]
Summary
Some rheumatoid arthritis (RA) patients achieve disease-modifying antirheumatic drug (DMARD)-free sustained remission. The absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA), is known to be associated with this outcome but further mechanisms underlying the chronic nature of RA are largely unknown. As joint damage is becoming less prevalent in patients with rheumatoid arthritis (RA), the focus is shifting to other disease outcomes such as disease-modifying antirheumatic drug (DMARD)-free sustained remission [1]. The strongest predictor for DMARD-free sustained remission is the absence of RA-specific autoantibodies, such as anticitrullinated protein antibodies (ACPA) [1, 2]. This suggests that patients who can achieve this outcome are inherently different
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