Efficacy and safety of sirolimus in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

BACKGROUND

Emerging evidence suggested a potential therapeutic role of targeting mTOR in the treatment of SLE. But most studies were observational studies with limited sample size or case reports.

OBJECTIVE

To evaluate the efficacy and safety of sirolimus in treatment of SLE by systematic review and meta-analysis.

METHODS

Systematic searches of Medline/PubMed, EMBASE, the Cochrane library and Scopus were performed. Original case reports, case series, observational studies and clinical trials reporting the efficacy or safety data on SLE patients treated with sirolimus were included. A random-effects meta-analysis was performed to calculate the pooled efficacy, when possible.

RESULTS

A total of 9 studies comprising 145 patients were identified. The exposure of sirolimus was 245.8 patient-years, with 1-3 mg/day adopted in majority studies. In 111 clinical active patients, the pooled decrease of SLEDAI, BILAG and prednisone dosage was 4.85 (95% CI 3.44-6.25), 1.98 (95% CI 0.23-3.74) and 13.17 mg/day (95% CI 0.71-25.63) respectively. 23 patients initiating sirolimus for active SLE yielded remission in 17 (73.9%) patients. In 22 quiescent lupus nephritis patients, 21 (95.5%) patients sustained remission. Hematological, mucocutaneous abnormalities and dyslipidemia were the most common adverse events. Early cessation due to side effects was reported in 9.28% (13/140) patients, most of the side effects were mild and recovered quickly after cessation.

CONCLUSIONS

Summary of the available datasets indicated sirolimus was promising and well-tolerated in the treatment of SLE. Further randomized controlled trials evaluating the potential benefits and risk of sirolimus in SLE are warranted.