Sirolimus for the treatment of patients with refractory connective tissue disease-related thrombocytopenia: a pilot study

Objective CTD-related immune thrombocytopenia (CTD-ITP) represents an unmet medical need because the drugs that are available are only partly effective and have considerable side-effects. The aim of this study was to assess the efficacy and safety of sirolimus in refractory CTD-ITP patients. Methods We did a single-arm, open-label, pilot study of sirolimus in patients with CTD-ITP unresponsive to, or intolerant of, conventional medications. Patients received oral sirolimus for 6 months at a starting dose of 0.5-1 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/ml. The primary efficacy end point was changes in platelet count, and overall response assessed according to the ITP International Working Group Criteria. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. Results Between November 2020 and February 2022, 12 consecutively hospitalized patients with refractory CTD-ITP were enrolled and prospectively followed. Of these, six patients (50%) achieved complete response, two (16.7%) achieved partial response, and four (33.3%) were no response under therapy. Three of four patients with primary Sjogren's syndrome and two of three patients with systemic lupus erythematosus achieved overall response. One of two patients with overlapping Sjogren's syndrome and systemic lupus erythematosus achieved complete response at 6 months. No severe drug-related toxicities were observed. Conclusion Our results do support sirolimus as an alternative regimen for refractory CTD-ITP patients, including systemic lupus erythematosus and primary SS.