Sirolimus Proven As Effective As Tacrolimus in SLE Treatment


Results showed equivalent effectiveness in disease control between the novel drug, sirolimus, and the classic immunosuppressant, tacrolimus, for the treatment of systemic lupus erythematosus.

Treatment of systemic lupus erythematosus (SLE) with sirolimus was as effective and well tolerated when compared with the classic immunosuppressant, tacrolimus, according to a study published in Lupus Science & Medicine.1 Further, results indicated the medication showed more serological improvement and better effects on glucocorticoid tapering.

“Sirolimus, also known as rapamycin, is an inhibitor of the mechanistic (or mammalian) target of rapamycin (mTOR). Studies show that it has both mechanical and clinical therapeutic effects on SLE,” investigators began. “Tacrolimus, which is a calcineurin inhibitor, has a similar structure to sirolimus but a different therapeutic target. Its efficacy for SLE treatment has been widely acknowledged.”

Eligible patients with clinically diagnosed and active SLE, measured by a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of ≥2, who were currently receiving either sirolimus or tacrolimus were recruited from China’s CSTAR registry and enrolled in this real-world cohort study. Patients were matched for sex, age, age of onset and diagnosis, and disease duration. Examinations at baseline and 4 follow-up visits (3, 6, 9, and 12 months) included demographics, clinical features, renal effectiveness, disease activity, steroid dosage, any changes in other immunosuppressants, such as hydroxychloroquine, and adverse events. Results were then analyzed and compared between treatment groups.

At baseline, investigators evaluated 52 patients from each cohort. Indicators of efficacy, including SLEDAI-2K scores, Physician’s Global Assessment (PhGA) scores, and those who were able to achieve remission were identical between both groups at all checkpoints (p≥0.05).

At month 3, the sirolimus group showed greater improvements in C3 (25% vs 8%) and C4 (35% vs 11%) levels when compared with the tacrolimus group. At month 6, results showed 31% improvement in the sirolimus group vs 5% the tacrolimus group in C3 and 58% vs 4% elevation in C4.

A higher number of patients receiving prednisone ≤7.5 mg/day was observed for the sirolimus group at all follow-ups when compared with the tacrolimus cohort (49% vs 18% with p=0.010, 68% vs 29% with p=0.015, 79% vs 33% with p=0.025, and 85% vs 35% with p=0.009, at 3, 6, 9 and 12 months, respectively).

Percentages of partial or complete renal remission and those with hematuria were also equal between both treatment groups. However, tacrolimus was able to better reduce urine protein at 6 months.

None of the patients switched medications during the 12-month period. However, 2 patients from each cohort added either sirolimus or tacrolimus to their treatment plan.

A total of 17 adverse events occurred during the 12-month period, including mild infections, mild renal insufficiency, skin rashes, gastrointestinal changes, and menstruation changes. Three adverse events were observed in the tacrolimus group, including mild infection, mild hemocytopenia, and loss of eyebrows and eyelashes. None of the patients discontinued either drug.

The small sample size limits the study. However, as sirolimus is a novel medication, future studies will presumably have more robust sample sizes. Additionally, serum sirolimus concentration was not reported and therefore its effect on adverse events or efficacy could not be evaluated. Antiphospholipid antibodies, which have been previously shown to be improved by sirolimus, were not collected at follow-up visits. Some bias may have occurred in reporting adverse events in the sirolimus cohort as investigators were unfamiliar with the effects. Due to disease activity and adverse effects being similar, investigators may have overestimated these events.

“We conducted the first study comparing the effectiveness and safety of sirolimus in the treatment of SLE with that of a classic immunosuppressant,” investigators concluded. “Sirolimus and tacrolimus showed equivalent effectiveness in disease activity control, and sirolimus showed better effectiveness in terms of serological improvement and glucocorticoid tapering. Sirolimus was well tolerated in patients with SLE. We believe that sirolimus is effective and safe for SLE treatment.”


Jiang N, Li M, Zhang H, et al. Sirolimus versus tacrolimus for systemic lupus erythematosus treatment: results from a real-world CSTAR cohort study. Lupus Sci Med. 2022;9(1):e000617. doi:10.1136/lupus-2021-000617

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