0937: Conventional Synthetic DMARDs Re-treatment for Rheumatoid Arthritis Flare During Drug-free Follow-up: Rate, Dynamics and Quality of Clinical Response

Emanuele Bozzalla Cassione¹, Iolanda Mazzucchelli², Terenzj Luvaro², Blerina Xoxi², Ludovico De Stefano², Garifallia Sakellariou², Silvia Grignaschi², Mehrad Mansoubi², Serena Bugatti², Carlomaurizio Montecucco² and Antonio Manzo³, ¹University of Pavia, IRCCS Policlinico San Matteo Foundation, Milano, Milan, Italy, ²University of Pavia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy, Pavia, Italy, ³IRCCS Policlinico San Matteo Foundation/University of Pavia, Pavia, Pavia, Italy

Background/Purpose: Drug-free (DF) remission, as a putative proxy of cure, has recently gained the attention of the scientific community as a desirable new target of therapy in rheumatoid arthritis (RA). Despite previous studies have suggested the feasibility of the DF approach in selected patients, the potential risks linked to the event of DF flare remain unclear. In this context, the actual rate, the quality, and the dynamics of clinical response after re-treatment remain three critical issues.

Methods: 116 RA patients in DF follow-up after the achievement of stable csDMARD-induced DAS28-ESR (DAS28) remission were evaluated every 3 months through complete clinical and US evaluations. Patients presenting a RA flare were re-treated with the same csDMARD introduced at the onset and followed up through a DAS-driven approach for 12 months. Flare was defined based on OMERACT definition. Cumulative incidence of achievement of DAS28 remission (< 2.6) and low disease activity (LDA)(< 3.2) after re-treatment was calculated. Time (months) until first DAS28 remission was compared between treatment at diagnosis and re-treatment after DF flare in individual patients.

Results: 55 patients displaying a DF flare across 60 months of follow-up were included in the current analysis. One patient was lost at follow-up after 6 months of re-treatment. The median (IQR) DAS28 at flare was 3.98 (3.56-4.61). The cumulative achievement of point DAS28 remission during follow-up after re-treatment was 55% (28 patients) at 3 months, 74,5% (41 patients) at 6 months, 89% (48 patients) at 9 months and 94,5% (51 patients) at 12 months. Differently, the cumulative achievement of low disease activity (treatment target) was 78% (40 patients) at 3 months, 93% (51 patients) at 6 months and 100% (54 patients) at 9 months. Among the 55 patients, 2 (3.6%) needed to introduce bDMARD (Abatacept and Certolizumab Pegol): one patient because of radiographic progression and the other on the bases of medical judgment despite achievement of LDA (both at 12 months of re-treatment). The median (IQR) time to first DAS28-ESR remission was 4 (2-9) after initial treatment at diagnosis and 3 (3-6) months after re-treatment for drug-free flare (p-value (0.196). No significant differences were observed between ACPA positive and negative patients in the time to first remission after initial treatment or after re-treatment. At individual level, the time to first remission after initial treatment and after re-treatment for flare showed a positive correlation (Spearman's rho 0.371, p=0.003), in particular in ACPA negative patients (spearman rho 0.536, p=0.007). None of the clinical and serological characteristics of flare appeared linked to a significant difference in the degree of response.

Conclusion: DAS-driven re-treatment with csDMARDs after drug-free flare allows to re-achieve remission or LDA in the majority of patients within 12 months. A minority of patients may however fail to achieve a secondary response pointing at the requirement of predictors. The recognized correlation between times to achieve remission after initial treatment and flare re-treatment suggests the possible existence of an individual response predisposition maintained across progressive disease stages.

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