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

Abstract

Background 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 0·1% 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 0·2% 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 0·2% 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. What's already known about this topic? Case studies indicate that 0·1-1% rapamycin ointment, 1% cream and 0·1% solution are effective against angiofibromas in tuberous sclerosis complex (TSC). The 0·1% solution causes skin irritation. What does this study add? This left-right comparative study confirmed that rapamycin 0·2% ointment and gel are effective in TSC compared with vehicle. In vitro percutaneous absorption is significantly better with the gel than the ointment. Significantly greater effects are observed in younger children. © 2013 British Association of Dermatologists.