American researchers have evaluated the benefit of sirolimus in the context of a prospective clinical trial in patients suffering from systemic lupus erythematosus resistant to the usual drugs.
People with systemic lupus erythematosus have dysfunction of certain white blood cells, T cells, related to activation of the mTOR pathway. Sirolimus is made up of rapamycin, a substance that inhibits the proliferation of these T lymphocytes.
Researchers at New York University evaluated the safety, tolerability and efficacy of sirolimus in patients with systemic lupus erythematosus, clinically active, and resistant or intolerant to usual treatments. Sirolimus reduces the activity of the disease after 12 months of treatment. Their results are published in the Lancet March 15, 2018.
Pathology assessment according to scores
The researchers evaluated, in patients meeting at least 4 of the 11 diagnostic criteria for SLE according to those defined by the American College of Rheumatology.
56 participants were treated with sirolimus for 12 months. The primary endpoint was decrease in disease activity assessed using the British Lupus Assessment Group (BILAG) Index and Systemic Lupus Erythematosus Activity Index (SLEDAI), 2 internationally validated indices.
Gradual improvement in disease scores
During the 12-month study, 11 of 40 eligible patients discontinued treatment due to intolerance (n = 2) or non-compliance (n = 9). Disease activity scores decreased in 16 (55%) of 29 patients who took treatment up to 12 months. After 1 year of treatment, the mean SLEDAI score fell from 10 to 4 and the mean score of the BILAG index fell from 28 to 17.
In addition, the average dose of prednisone necessary to control the activity of the disease increased from 7 to 2 mg per day after 12 months of treatment. Liver function and the number of T cells remained constant. In contrast, moderate reductions in HDL cholesterol, neutrophil count and hemoglobin were observed. The platelet count was slightly elevated.
A 12-month treatment with sirolimus makes it possible to obtain a progressive improvement in the activity of lupus disease, but controlled trials against standard treatment are justified to better define the place of mTOR blockade in the treatment of lupus.
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