FRI0215 SIROLIMUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS RELATED THROMBOCYTOPENIA (SLE-TP): A SINGLE-ARM, OPEN-LABEL CLINICAL TRIAL
Authors: Chanyuan Wu, Qian Wang, LI Mengtao, Xiaofeng Zeng
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Autoimmune thrombocytopenia (AITP) is common in systemic lupus erythematosus (SLE) patients and may be refractory to conventional therapies. SLE related thrombocytopenia (SLE-TP) patients have T-cell dysfunction that was reported to be associated with the activation of the mammalian target of rapamycin (mTOR). Rapamycin (RAPA) inhibits antigen-induced T-cell proliferation and has been developed as a medication named sirolimus. <h3>Objectives:</h3> We assessed safety, tolerance, and efficacy of sirolimus in a prospective, open-label clinical trial. <h3>Methods:</h3> We did a single-arm, open-label study of sirolimus in patients with refractory SLE-TP unresponsive to, or intolerant of, conventional medications at Peking Union Medical College Hospital (PUMCH, Beijing, China). We enrolled refractory TP patients (aged ≥18 years) with systemic lupus erythematosus (SLE) who visited our referral center since September 2017. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of lupus, such as RPGN, NPLE or PAH and patients with uncured infection. All eligible participants had signed informed consents. Patients received oral sirolimus at a starting dose of 2 mg per day for 3 days and a sequential dose of 1mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6–15 ng/mL. Patients were treated with sirolimus for 6 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was complete remission rate and partial remission rate at the sixth month. The secondary efficacy endpoint was thea remission rates at the third month. The efficacy endpoints were assessed in all patients who completed 3 or more months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. <h3>Results:</h3> Between September 2017 and November 2018, 12 lupus patients (1 male and 11 female) were enrolled with an average age of 33.3y, average disease duration of 8.4 years. All patients haven't achieved remission with front-line therapy, including corticosteroids, intravenous immunoglobulin, and immunomodulatory agents, such as azathioprine, FK506, mycophenolate mofetil, and cyclosporine. After sirolimus therapy (2 weeks to 6 months), 5 of 12 patients achieved CRR. 11 patients have finished 4 months' assessment, and 9 of them achieved remission. One patient had mild oral ulcers and no other complications were noted. The study is still in regular follow-up. There will be more results and conclusions in the later period. <h3>Conclusion:</h3> Sirolimus is effective for the treatment of refractory SLE-TP and can be a choice of the second-line treatment. Further prospective studies are needed to evaluate sirolimus as a therapeutic option for SLE-TP and to monitor for potential long-term side effects. <h3>References:</h3> [1] Perl A. Nat Rev Rheumatol 2016; 12: 169–82. [2] Morel L. Nat Rev Rheumatol 2017; 13: 280–90. [3] Oaks Z, et al. Arthritis Rheumatol 2016; 68: 2728–39. [4] Oaks Z, et al. Curr Rheum Rep 2016; 18: 73. [5] Zhi-Wei Lai, et al. Lancet 2018 Mar 24;391(10126):1186-1196. [6] Desmond Y.H. Yap, et al. J Rheumatol. 2018 Dec;45(12):1663-1670. <h3>Acknowledgement:</h3> None <h3>Disclosure of Interests:</h3> None declared