FRI0136 THE EFFICACY AND SAFETY OF SIROLIMUS IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: A RANDOMIZED AND PARALLEL-CONTROLLED CLINICAL TRIAL
Authors: Jia Wang, Sheng-xiao Zhang, Fang Yuan Hu, Xiao-Juan Zheng, Ting Cheng, Na-Na Yu, Wen-Xian Yang, Chong Gao, Hong-Yan Wen, LI Xiao-Feng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> We have reported previously that the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA)<sup>[</sup><sup>1-3</sup><sup>]</sup>, challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs, which would be able to provide new strategy and target for the treatment of RA<sup>[</sup><sup>4</sup><sup>]</sup>. <h3>Objectives</h3> To investigate efficacy and safety of sirolimus combined with conventional immunosuppressants for RA treatment. <h3>Methods</h3> In this non-blinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2:1 ratio. The demographic features, clinical manifestations and laboratory indicators including peripheral blood lymphocyte subgroups and CD4<sup>+</sup>T subsets were compared before and after the treatment. <h3>Results</h3> Finally, 37 patients in sirolimus group and 18 in conventional treated group completed 6-month study. By 24 weeks, the patients with sirolimus experienced the significant reduction in disease activity indicators including DAS28, ESR, the number of tender joints and swollen joints (<i>p</i>&lt;0.001). Notably, they had a higher level of Tregs as compared those with conventional therapy alone (<i>p</i>&lt;0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usages of immunosuppressants for controlling disease activity were decreased as compared with conventional group with no difference in blood routine, liver and renal functions both before and after the treatment of sirolimus and between two groups (<i>p</i>&gt;0.05). <h3>Conclusion</h3> Low-dose sirolimus immunoregulatory therapy selectively up-regulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without over-treatment and evaluable side effect. The further study is required using a large sample of RA patients treated with sirolimus for longer period. <h3>References</h3> [1] Komatsu N, Takayanagi H. Arthritogenic T cells in autoimmune arthritis[J]. The international journal of biochemistry &amp; cell biology, 2015, 58:92-96.doi:10.1016/j.biocel.2014.11.008. [2] Morita T, Shima Y, Wing JB, et al. The Proportion of Regulatory T Cells in Patients with Rheumatoid Arthritis: A Meta-Analysis[J]. PloS one, 2016, 11(9):e0162306.doi:10.1371/journal.pone.0162306. [3] Spence A, Klementowicz JE, Bluestone JA, et al. Targeting Treg signaling for the treatment of autoimmune diseases[J]. Current opinion in immunology, 2015, 37:11-20.doi:10.1016/j.coi.2015.09.002. [4] Perl A. Activation of mTOR (mechanistic target of rapamycin) in rheumatic diseases[J]. Nature reviews Rheumatology, 2016, 12(3):169-182.doi:10.1038/nrrheum.2015.172. <h3>Acknowledgement</h3> No <h3>Disclosure of Interests</h3> None declared