First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex

Abstract

SummaryBackground Tuberous sclerosis complex (TSC) is an autosomal dominant disorder causing multiple hamartomas. Treatment of TSC lesions with mammalian target of rapamycin inhibitors is effective. Recently, several reports have shown the efficacy of topical rapamycin (sirolimus) for angiofibromas. However, almost all studies have been case studies and the 0Á1% solution caused skin irritation. A comparative study of topical rapamycin and a vehicle has not yet been reported. Objectives To compare the efficacy of topical rapamycin formulation with that of vehicle for angiofibromas. Methods A left-right comparative study between rapamycin 0Á2% topical formulation and vehicle was conducted in 11 patients with TSC. Two formulations, an ointment and a gel, were prepared and in vitro percutaneous absorption of rapamycin was determined. Results In vitro percutaneous absorption of rapamycin was significantly greater with the gel compared with the ointment. In the clinical study, the rapamycin-treated cheek showed significant improvements relative to the vehicle-treated cheek in all outcome measures after 12 weeks of treatment. The improvement was particularly remarkable in children aged ≤ 10 years. No side-effects were noted, and rapamycin was not detected in the blood of the patients. Conclusions Topical rapamycin was significantly effective against angiofibromas. Both formulations used were effective and safe. The 0Á2% gel is especially useful because of its better skin penetration and low irritancy. Initiation of topical rapamycin therapy in early childhood would be beneficial for patients with TSC.

Topical rapamycin for angiofibromas in paediatric patients with tuberous sclerosis: Follow up of a pilot study and promising future directions

“…[2][3][4][5][6][7][8][9][10][11][12][13] The articles were limited to those available in the English language and they were read, and any relevant articles referred to in the references were also included in the study. Of these, 11 were case series and one was a review article.…”

Sustained Effects of Sirolimus on Lung Function and Cystic Lung Lesions in Lymphangioleiomyomatosis

“…Sirolimus and everolimus, two immunosuppressant compounds that inhibit mTOR (12)(13)(14), are effective in decreasing the size of renal angiomyolipomas in patients with TSC or LAM (15)(16)(17), and reducing the size of giant cell astrocytomas and the severity of skin angiofibromas in patients with TSC (18)(19)(20). Treatment with sirolimus for 1 year decreased the rates of decline in FVC and FEV 1 and improved quality of life (21).…”

Topical rapamycin in facial angiofibromas: patients satisfaction versus objective response, and a literature review

“…Several studies have reported that sirolimus plasmatic concentration remains undetectable even in daily application (3,5,6,10,11). These determinations were not made in our patients.…”

“…On one hand the average age of our series (40,25) was older than the reviewed in the literature [16 (3), 17,9 (4), 21,77 (5), 20,5 (6), 8,5 (7), 13,5 (8), 17,6 (11), 11 (12), 27 (13), 10,6 (14)]. In fact it is supposed that the younger patients have an earlier and greater response to topical rapamycin (4,7,11,15). It is possible that FA in children and teenagers are less fibrotic than those of older patients in which fibrosis is established.…”