096 Safety and efficacy of sirolimus gel therapy for patients with TSC involving facial skin lesions in a long-term clinical trial

Abstract

Tuberous sclerosis complex (TSC), an autosomal dominant genetic disorder caused by the constitutive activation of the mTORC1 signaling pathway, gives rise to hamartomas in various organs including the skin. Facial angiofibromas (AF)—the most predominant manifestations among skin lesions—are observed in about 75% of TSC patients. The progression of AF can cause severe disfigurement, thus adversely affecting their quality of life. We conducted a multicenter, long-term, open-label, uncontrolled clinical trial of the sirolimus gel in 94 patients with TSC involving facial skin lesions (angiofibromas, cephalic plaques, and hypomelanotic macules). The primary endpoint was the rate of adverse event (AE)-caused discontinuation. The main secondary endpoint was the efficacy of the gel. The independent review committee adjudicated the efficacy of the gel according to the 6-category criterion based on the photographs of skin lesions that were taken during the first 12 months of the trial. The rate of AE-caused discontinuation was 2.1% (2/94 patients). Furthermore, application site irritation and dry skin occurred relatively frequently. However, none of drug-related AEs was serious, and most AEs resolved rapidly. The response rates of angiofibromas, plaques, and hypomelanotic macules were 78.2% (95% CI: 68.0-86.3%), 66.7% (95% CI: 51.1-80.0%), and 72.2% (95% CI: 46.5-90.3%), respectively. We conclude that the gel had good long-term tolerability and was effective for TSC facial skin lesions.