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

Abstract

ObjectiveThe effectiveness and safety of sirolimus for SLE treatment have been shown in some uncontrolled studies. However, a comparison of sirolimus with other classic immunosuppressants has not been reported. We conducted the study to compare the effectiveness and safety of sirolimus versus tacrolimus for SLE treatment.MethodsA real-world cohort study was conducted. Patients with clinically active SLE who were prescribed sirolimus or tacrolimus were enrolled. Propensity score matching was used to ensure equivalent disease conditions and background medications. SLE disease activity indices, serological parameters, steroid doses, modification of other immunosuppressants, renal effectiveness and adverse events were compared between the two groups at 3-month, 6-month, 9-month and 12-month follow-up visits.ResultsData from 52 patients in each of the sirolimus and tacrolimus groups were analysed. Indices regarding the effectiveness of sirolimus, including Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores, physician’s global assessment (PhGA) scores, and proportion of patients with SLEDAI-2K reduction of ≥4 and PhGA increase of <0.3, were equivalent to those of tacrolimus at all follow-up timepoints (all p≥0.05). Greater improvements in complement levels were observed in the sirolimus group at 3 and 6 months. Higher percentages of patients with prednisone doses ≤7.5 mg/day were observed in the sirolimus group at all timepoints. Seventeen adverse events in the sirolimus group were recorded. None was severe or led to drug discontinuation.ConclusionsOverall, sirolimus was as effective as tacrolimus in the treatment of SLE. Sirolimus had better effects on serological improvement and glucocorticoid tapering. Sirolimus was well tolerated in patients with SLE.

Predicting the effect of sirolimus on disease activity in patients with systemic lupus erythematosus using machine learning

“…Ji et al 7 indicated sirolimus was promising and well‐tolerated in the treatment of SLE. Jiang et al 1 found sirolimus was as effective as tacrolimus for treating SLE and had better tolerance in patients with SLE. However, the quantitative influence of sirolimus on disease activity in patients with SLE remained unknown, especially how could sirolimus be administered appropriately to reduce disease activity in SLE.…”

“…Systemic lupus erythematosus (also known as SLE or lupus) was a chronic inflammation of the autoimmune system that affected skin, joint, kidney, heart, lung, nervous system or other organs of the body, which usually leaded to poor life quality and even death 1–3 . At present, the clinical treatment of SLE mainly included conventional immunosuppressants, antimalarials, glucocorticoids and biologics, among which several drugs had been shown to be effective in the treatment of SLE 4,5 .…”

“…At present, the clinical treatment of SLE mainly included conventional immunosuppressants, antimalarials, glucocorticoids and biologics, among which several drugs had been shown to be effective in the treatment of SLE 4,5 . However, considering the huge adverse reactions of current drugs and the great heterogeneity of the disease itself, more safe and effective drugs need to be further searched 1 …”

Trained immunity as a possible newcomer in autoinflammatory and autoimmune diseases pathophysiology

“…Metabolic changes impacting DNA methylation/demethylation have been reported in lupus patients (93) and mTOR implications are also reported to be involved in SLE patients (94,95). Inhibitors of mTOR like sirolimus and everolimus have proven effective in the treatment of lupus (96,97). Metabolic regulation has been shown to be effective in a lupus mouse model and PBMCs from lupus patients to alleviate symptoms through an mTOR and NLRP3 regulation effect (98).…”

Glycolysis in Innate Immune Cells Contributes to Autoimmunity

“…In another trial of pediatric patients with SLE, most achieved durable remission with sirolimus treatment (163). Moreover, sirolimus has greater advantages for serological reduction and glucocorticoid tapering, compared to the classic immunosuppressant tacrolimus, in treating SLE (164).…”