Effect of sirolimus on connective tissue disease related refractory thrombocytopenia: clinical efficacy and immunomodulatory mechanism.

Introduction: Connective tissue diseases (CTDs), which include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjogren's syndrome (SS), and so on, represent a group of autoimmune disorders that predominantly affect the body's connective tissues. Aim: This study aimed to investigate the clinical efficacy of sirolimus in patients with connective tissue disease complicated with refractory thrombocytopenia (CTD-RTP) and its effect on immune regulation. Material and methods: A retrospective study was conducted on 13 patients diagnosed with CTD-RTP who were treated with oral sirolimus for 6 months, starting with a daily dose of 1 mg. Changes in platelet counts, T cell lymphocyte subsets, regulatory T cells (Tregs), B cells, and cytokine levels were assessed from baseline to the end of the 6-month treatment. From November 2020 to December 2023, 13 patients with CTD-RTP were consecutively enrolled and monitored. Results: The treatment was well tolerated with no severe drug-related toxicities were reported. After 3 months of sirolimus treatment, 7 patients exhibited a positive response (PR), with 1 patient achieving complete response (CR), resulting in an overall response rate of 61.5%. Continued treatment for 6 months led to further improvements, with the total effective rate reaching 76.9%. Importantly, there was a significant increase in peripheral blood Tregs after treatment compared with the baseline level. Conclusions: Sirolimus is an effective and safe treatment option for CTD-RTP patients, and its effect may be related to its ability to increase the level of regulatory T cells in peripheral blood.