Koenig MK, et al. - Researchers investigated whether topical rapamycin is effective and safe for treatment of tuberous sclerosis complex (TSC)-related facial angiofibromas. Findings suggested the utility of topical rapamycin in treating TSC-related facial angiofibromas. The preferred dose was 1% once daily in this trial.

Methods

• Researchers performed a prospective, multicenter, randomized, double-blind, vehicle-controlled trial with 6 monthly clinic visits enrolling 179 patients with TSC-related facial angiofibromas not treated within 6 months from May 2012 to March 2014 in 9 clinical sites in the United States and 1 in Australia.
• They randomized patients (1:1:1) to topical formulation containing 0.3 g per 30 g (1%) rapamycin, 0.03 g per 30 g (0.1%) rapamycin, or vehicle alone.
• Participants were asked to apply 1.0 mL to designated areas daily at bedtime.
• Main outcomes and measures included Angiofibroma Grading Scale (AGS) change from baseline scored from photographs by independent masked dermatologists.
• Adverse events (AEs) and serum rapamycin levels were included in safety analyses.

Results

• The primary analysis population comprised of all 179 patients that were randomized (99 [55.3%] female); 59 in the 1% rapamycin group, 63 in the 0.1% rapamycin group, and 57 in the vehicle-only group.
• The mean age of 20.5 years (range 3-61 years) was reported.
• Both 1% and 0.1% rapamycin group demonstrated clinically meaningful and statistically significant improvement in facial angiofibromas when compared to the vehicle-only control group; for 1% vs 0.1% rapamycin, most of the improvement was realized within the first month.
• Mean improvement in AGS for 1% rapamycin was 16.7 points compared with 11.0 for 0.1% rapamycin and 2.1 points for vehicle only at 6 months, (P < .001 for 1% and 0.1% vs vehicle only).
• End-of-treatment photos were rated “better”, relative to baseline, for 81.8% of patients in the 1% rapamycin group, compared with 65.5% for those in the 0.1% rapamycin group and 25.5% for those in the vehicle-only group (P < .001, all 3 pairwise comparisons).
• With no measurable systemic absorption, topical rapamycin was noted to be generally well-tolerated.
• With respect to apparent drug-related adverse effects, findings revealed 10% or less incidence of application site discomfort and/or pain, pruritus, erythema, and irritation.
• No drug-related moderate, severe, or serious events were noted; nearly all AEs noted were mild.