Background/Purpose:

Early diagnosis and treat-to-target strategies with conventional DMARDs in rheumatoid arthritis (RA) have allowed the achievement of remission in a significant percentage of the cases in daily practice. Whether and in which patients treatments can be suspended with maintenance of health is currently unclear. In this study, we investigated the outcomes of methotrexate (MTX) suspension and predictors of disease recurrence in a real life single centre cohort of early RA patients followed prospectively under DMARD- and glucocorticoid-free conditions.

Methods:

All RA patients included in this current prospective observational study derived from the Pavia’s Early Arthritis Clinic and were treated according to a DAS-driven step-up protocol with MTX in monotherapy. Patients achieving stable DAS28 remission and fulfilling the following criteria were eligible for drug suspension: 1) fulfillment of the 2010 ACR/EULAR classification criteria for RA within 12 months from baseline visit; 2) MTX introduced within 12 months from symptoms’ onset; 3) ≥24 months of continuative MTX; 4) DAS28 <2.6 for ≥6 months in the absence of glucocorticoids. Patients were followed-up at three-months intervals through complete clinical and ultrasonographic (hands-feet) assessments. Radiographs were repeated annually. Treatment was reintroduced in case of DAS28≥3.2 in a single occasion or 3.2<DAS28≥2.6 for >6 months.

Results:

Seventy RA patients with at least 6 months of follow-up following DMARDs discontinuation were considered. Baseline stratification according to remission stringency showed SDAI remission in 57/70 (81.4%), ACR/EULAR Boolean remission in 52/70 (74.3%) and absence of clinical and ultrasonographic synovitis (SJC44=0 and power Doppler signal in hands-feet=0) in 23/70 (32.9%). Treatment restart due to disease recurrence was observed in 28/70 patients (40%) over 2 years of follow-up, with a median (IQR) time until retreatment of 6 (6-10.5) months. None of the clinical characteristics at the time of diagnosis showed predictive significance. Worsening of disease activity was more likely to occur in patients not in remission according to the SDAI (HR [95% CI] 2.56 [1.15-5.70], p=0.02). Below this threshold, remission stringency failed to show any protective role, with 10/23 (43.5%) patients showing disease recurrence despite absence of clinical and subclinical synovitis at the time of drug suspension. Among patients in SDAI remission, IgG ACPA were the only predictor of relapse, independent of remission duration and the residual inflammatory degree at baseline (HR [95% CI] 4.38 [1.50-12.89], p=0.008). IgG ACPA-IgM rheumatoid factor (RF) double positivity showed increased predictive ability (HR [95% CI] 7.11 [2.38-21.25], p<0.001).

Conclusion:

Despite deep and sustained remission following early treatment and treat-to-target approaches in routine clinical care, DMARD suspension appears a feasible option only in a proportion of RA patients. The autoimmune status is the strongest predictor of disease reactivation in patients achieving stringent clinical and ultrasonographic control of the inflammatory process.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prognostic-significance-of-residual-inflammation-and-autoantibodies-for-disease-relapse-upon-dmard-suspension-in-patients-with-rheumatoid-arthritis-in-sustained-remission-after-das-driven-therapy/