Background/Purpose: Early diagnosis and treat-to-target strategies with synthetic conventional DMARDs in rheumatoid arthritis (RA) have allowed the achievement of remission in a significant percentage of the cases in daily practice. Due to the scarcity of data on long-term outcomes, the feasibility of a personalized approach for early identification of patients in which treatments can be suspended is currently unclear. Here, we investigated the predictors of disease recurrence in a real life cohort of early RA patients followed under csDMARD- and glucocorticoid-free conditions. Based on previous studies, we hypothesized a primary predictive value of synovial ultrasound features at baseline as markers of residual sub-clinical inflammation in peripheral joints.

Methods: One hundred and eighteen RA patients from the Pavia Early Arthritis Clinic (EAC) and treated according to a DAS-driven protocol with MTX were referred to a drug-free follow-up. Referral was based on the fulfillment of the following inclusion criteria: 1) fulfillment of the 2010 ACR/EULAR classification criteria for RA within 12 months from first visit in the EAC; 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 the case of flare, defined according to the OMERACT definition. Predictors of time-to-flare were analyzed with univariate and multivariate Cox-regression.

Results: One-hundred-sixteen patients with at least 3 months of follow-up following DMARDs discontinuation were considered for the analysis (total person-months: 3231). Treatment re-introduction due to disease flare was observed in 55 patients at the time of analysis, with a median (IQR) time until retreatment of 9 (3-18) months. None of the clinical characteristics at the time of diagnosis showed predictive significance. Stratification of the patients according to the degree of remission stringency at the time of withdrawal demonstrated a protective value of the SDAI (≤3.3) (HR [95% CI] 0.45 [0.23-0.89], p=0.02), but not of ultrasound remission alone (power Doppler score=0) or combined with clinical thresholds. Multivariable analyses in patients in remission according to the SDAI, demonstrated that IgG ACPA were the only predictor of time-to-flare, independent of remission duration and the residual inflammatory degree at baseline (clinical and ultrasonographic) (HR [95% CI] 5.7 [3.25-10.04], p >0.0001). Residual power Doppler positivity at baseline did not reveal a predictive value for flare in both ACPA positive and negative patients.

Conclusion: csDMARD suspension after intensive treatment strategies and the achievement of stringent clinical remission appears a feasible option at long-term only in a proportion of RA patients. The autoimmune status is the strongest predictor of time to 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/baseline-predictors-of-disease-flare-upon-csdmard-withdrawal-in-patients-with-rheumatoid-arthritis-in-sustained-remission-after-das-driven-therapy-role-of-the-systemic-autoimmune-status-and-periphera/