THU0176 Efficiency and safety of rapamycin combined with low-dose IL-2 treatment compared with methotrexate in patients with rheumatoid arthritis

Background The molecular target rapamycin (mTOR) signaling can regulate between effector and regulatory T cell lineage commitment [1]. Rapamycin, the inhibitor of mTOR, has appeared to be a new therapy for several autoimmune diseases, such as systemic lupus erythematosus [2]. Objectives To evaluate whether rapamycin is beneficial in patients with Rheumatoid Arthritis (RA), and compared with Methotrexate in efficiency and safety. Methods Fifty-eight DMARDs-naive RA patients were enrolled, thirty-eight were treated with Rapamycin (0.5 mg every 2 days, combined with IL-2 50WIU per day for 5 days), the others with Methotrexate (10mg per week) taken as control. Clinical improvement and immunological assessments were performed at baseline, 1 and 12 weeks. Treatment group assessed CD4+ T cell subsets by flow cytometry at baseline, 1 and 12 weeks. Results We enrolled 58 patients. At baseline, patients had a mean DAS28 of 3.34 (0.81). Rapamycin group and Methotrexate group included 38 and 20 patients, respectively, with no significant differences in baseline characteristics. At 1 week, the mean DAS28 after Rapamycin treatment (2.43 [0.77]) and Methotrexate (2.25 [0.86]) was not significantly different (P=0.43). Same as ESR (24.74 [24.53], 21.76 [24.27], P=0.66). The dose of glucocorticoid during hospitalization of rapamycin treatment group (720.8 [554.3]) was lower than Methotrexate (1202.3 [943.1], P=0.042). The length of hospital stay of Rapamycin (14.5 [3.9]) was lower than Methotrexate (21.0 [3.8], P Conclusions Rapamycin combined with the low-dose IL-2 appears to be a safe and effective therapy for RA, by a rapid increase of circulating Treg cells and a correction of the ratio of Th17/Treg cells, which has gotten a same response compared with Methotrexate. References Zheng Y. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment.[J]. Immunity, 2009, 30(6):832–844. Fernandez D, Bonilla E, Mirza N, et al. Rapamycin Reduces Disease Activity and Normalizes T Cell Activation–Induced Calcium Fluxing in Patients With Systemic Lupus Erythematosus[J]. Arthritis & Rheumatology, 2006, 54(9):2983–2988. Disclosure of Interest None declared