0938: 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 Peripheral Joint Ultrasound Across a 5-year Follow-up

Antonio Manzo¹, Emanuele Bozzalla Cassione², Iolanda Mazzucchelli³, Silvia Grignaschi³, Blerina Xoxi³, Terenzj Luvaro³, Ludovico De Stefano³, Garifallia Sakellariou³, SERENA BUGATTI³ and Carlomaurizio Montecucco⁴, ¹IRCCS Policlinico San Matteo Foundation/University of Pavia, Pavia, Pavia, Italy, ²University of Pavia, IRCCS Policlinico San Matteo Foundation, Milano, Milan, Italy, ³University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Pavia, Italy, ⁴Department of Rheumatology, IRCCS Policlinico S. Matteo Foundation, University of Pavia, Pavia, Italy

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.

Disclosures: A. Manzo, Pfizer, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Eli Lilly, Gilead, Sanofi; E. Bozzalla Cassione, Bristol-Myers Squibb(BMS); I. Mazzucchelli, None; S. Grignaschi, None; B. Xoxi, None; T. Luvaro, None; L. De Stefano, Sobi; G. Sakellariou, Bristol-Myers Squibb(BMS), AbbVie/Abbott, Novartis, Sobi, Galapagos; S. BUGATTI, Pfizer, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Eli Lilly, Gilead, Sanofi; C. Montecucco, AbbVie/Abbott, Bristol-Myers Squibb(BMS), Eli Lilly, Gilead, Roche, Pfizer, Sanofi.