Clinical efficacy and safety of sirolimus in systemic lupus erythematosus: a real-world study and meta-analysis

Abstract

Objective: To provide real-world data and summarize current clinical evidence on the efficacy and safety of sirolimus in active systemic lupus erythematosus (SLE) patients. Methods: This was a prospective real-world clinical study. Included SLE patients should have Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ⩾ 2. They were treated with sirolimus and followed up regularly. The SLEDAI-2K, Physician Global Assessment (PGA), serological activity indices, and remission of organ manifestations were evaluated. We also performed a meta-analysis to integrate current evidence of sirolimus in SLE. Results: A total of 49 patients were included in the final analysis. After treatment, the SLEDAI-2K (6.2 ± 3.1 versus 4.0 ± 3.4, p = 0.001) decreased significantly, and the prednisone dosage was tapered successfully (9.9 ± 8.8 mg/day versus 5.9 ± 4.0 mg/day, p = 0.002). Serological activity indices also improved [complement 3 (C3): 0.690 ± 0.209 g/l versus 0.884 ± 0.219 g/l, p < 0.001; complement 4: 0.105 ± 0.059 g/l versus 0.141 ± 0.069 g/l, p < 0.001; anti-dsDNA antibody, 200 ± 178 IU/ml versus 156 ± 163 IU/ml, p = 0.022]. The remission proportions of arthritis, skin rash, and thrombocytopenia were 100%, 88.8%, and 46.2%, respectively. A total of 41.2% of lupus nephritis (LN) patients achieved renal remission, but the average 24-h urine protein level was not significantly changed. Meta-analysis enrolled five studies with 149 patients included, and revealed similar results regarding the changes of SLEDAI-2K [−3.5 (−5.0, −2.1)], C3 [0.224 (0.136, 0.311) g/l] and daily dosage of prednisone [−12.7 (−19.9, −5.6) mg/day]. Conclusion: Sirolimus might be effective and tolerated in SLE. The role of sirolimus in LN requires further study.

Successful treatment of sirolimus in a Chinese patient with refractory LN and APS: a case report

“…Increasing evidence regarding the use of the mTOR inhibitor rapamycin (also called sirolimus) as a new potential treatment regimen for LN has been gained from animal models since 2008 3 , 4 and patient trials since 2009. 5 – 9 A single-arm, open-label, phase 1/2 trial and a real-world study confirmed the safety and efficacy of oral sirolimus in the treatment of SLE. 10 , 11 Retrospective studies reported LN patients who responded to sirolimus as an induction or maintenance therapy.…”

“…Among 17 active LN patients who were treated with sirolimus, 7 had a renal response by 3 to 9 months, whereas another 10 patients experienced worsening of proteinuria. 9 The discrepancy in the treatment response might be explained by the different inclusion criteria. PUMCH enrolled refractory patients with either intolerance or a poor response to the previous immunosuppressants.…”

Sirolimus versus tacrolimus for systemic lupus erythematosus treatment: results from a real-world CSTAR cohort study

“…Its effectiveness and safety in SLE treatment have been reported in uncontrolled studies. [13][14][15][16] However, a comparison of sirolimus with other classic immunosuppressants has not been reported. In our study, tacrolimus was chosen as the positive control due to its structural similarities with sirolimus and its proven effectiveness as a medication recommended for SLE treatment according to several guidelines.…”

“…Studies show that it has both mechanical and clinical therapeutic effects on SLE. [10][11][12][13][14][15][16] However, as a newly used medicine for SLE, more evidence and comparisons with other immunosuppressants are necessary to prove its efficacy and safety.…”

miR-20a Overexpression in Adipose-Derived Mesenchymal Stem Cells Promotes Therapeutic Efficacy in Murine Lupus Nephritis by Regulating Autophagy

“…The activated mTOR pathway has been detected in LN and has emerged as a central pathway for pathogenesis and treatment with rapamycin or other mTOR inhibitors, displaying protective and beneficial effects for LN [ 15 , 16 ]. In our previous study, ADSC (passage 4) transplantation prevented LN development and ameliorated already-established disease via the mTOR/HIF-1 α signal pathway [ 10 ].…”