LAUSR

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that results in destruction of joint cartilage and bone. However, many patients do not achieve satisfactory disease control by current therapy with high risk of adverse reactions. We have reported that absolute number of peripheral regulatory T (Treg) cells reduced in RA patients (EULAR Abstract). Moreover, rapamycin has been reported to inhibit differentiation of Th17 and promote growth of FoxP3 +Treg cells by inhibiting mTOR pathway [1]. Objectives To observe the therapeutic efficacy of rapamycin on the reduction of disease activity, increase in Tregs and decrease in Th17 to restore balance of Th17/Treg cells in RA patients with high disease activity (DAS28 ≥2.6). Methods Fifty RA patients who treated with two kinds of DMARDs for more than half a year did not achieve remission (DAS28 ≥2.6) were enrolled and were treated with rapamycin at a dose of 0.5 mg every 2 days for 24 weeks. The absolute number of CD4 +T cell subsets in peripheral blood from these patients were assessed by flow cytometry combined with internal standard beads before the treatment as baseline and at week 24 after treatment. Meantime, the DAS28, the dosage of corticosteroids and immunosuppressant were also recorded. Results Rapamycin treatment reduced the disease activity and induced remission (DAS28<2.6) in 44.9% of active RA patients. Their DAS28 was reduced from a median 2.9 (at week 0) to 1.9 (at week 24) (P<0.001) and the absolute number of peripheral Treg cells was increased from 27.14±15.11 cells/µl (at week 0) to 36.59±17.23 cells/µl (at week 24) (p=0.002). The ratios of Th17/Treg cells also had a significant decrease from 0.36±0.29 at baseline to 0.27±0.20 at week 24 (P<0.041). In contrast, the decrease in the absolute number of Th17 cells was not statistically significant (p=0.846). After the treatment, the proportion of patients taking glucocorticoids decreased from 66.0% to 64.0% and the mean dosage of prednisone decreased from 9.89 mg/d to 7.70 mg/d. And the usages of DMARDs were also reduced (P<0.001). Conclusions Rapamycin combined with low level of conventional therapy effectively reduced disease activity and induced remission among RA patients who received long-term conventional treatment without remission (DAS28 ≥2.6) by increasing the absolute number of Treg cells and restoring the balance of Th17 cells and Treg cells. As the research progresses, rapamycin is likely to become a promising therapeutic candidate. Reference [1] Shan J, Feng L, Sun G, et al. Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells. Immunobiology2015;220(4):510–517. Disclosure of Interest None declared