The safety and efficacy of topical rapamycin-calcitriol for the treatment of tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs) was supported by study data published in the British Journal of Dermatology.
Investigators in Taipei, Taiwan, conducted a 36-week trial of topical rapamycin-calcitriol for patients with TSC-related FAs. The trial comprised 3, 12-week periods. Period 1 (weeks 0-12) was a double-blind, left-right-randomized, split-face comparison study in which topical rapamycin 0.1% or calcitriol 0.0003% single-agent therapy was compared against rapamycin-calcitriol combination therapy. During Period 2 (weeks 13-24), patients were rerandomized to use their most effective Period 1 agent twice daily for 12 weeks. Treatment was discontinued for Period 3 (weeks 25-36), during which follow-up assessments were conducted to assess FA recurrence.
The primary outcome measure was change in partial or total Facial Angiofibroma Severity Index (mFASI) scores at baseline and week 12. Investigators also assessed reduction in patient global visual analogue scale (PG-VAS) score between baseline and week 12. The Wilcoxon signed-rank test was used to assess relative efficacy of each treatment modality. Adverse events were monitored throughout the 36-week trial.
A total of 52 patients were enrolled, of whom 32 were women. Mean age was 26.7 years; age range was 7 to 67 years. Mean changes in mFASI at week 12 vs baseline were -0.92, -0.44, and -1.09 for rapamycin monotherapy (P ≤.001), calcitriol monotherapy (P =.039), and rapamycin-calcitriol combination therapy (P ≤.001), respectively. Significant PG-VAS reduction at week 12 was observed for each of the rapamycin (-3.6 ± 2.13), calcitriol (-4.21 ± 2.04), and rapamycin-calcitriol (-4.14 ± 2.15) subgroups (all P ≤.001).
Per the Wilcoxon rank test, rapamycin-calcitriol combination therapy significantly outperformed calcitriol monotherapy, but not rapamycin monotherapy, for mFASI score reduction. However, compared with rapamycin monotherapy, the combination gel demonstrated faster improvement in erythema and greater overall reduction of papule elevation. Continuous treatment with rapamycin-calcitriol therapy resulted in borderline significantly reductions in papule elevation, erythema, and overall mFASI score between weeks 12 and 24. Patients treated with rapamycin-calcitriol during Period 2 also demonstrated longer durability after discontinuation than patients treated with rapamycin alone. The reduction of mFASI between baseline and week 36 was significant in the rapamycin-calcitriol subgroup (-0.36 ± 0.95; P =.005), although not the rapamycin subgroup (-0.6 ± 1.02; P =.064). Overall, 47 patients completed all 3 study periods; withdrawal was not associated with treatment-related adverse events. Treatment was well-tolerated for all 3 formulas. The most commonly reported side effect was mild to moderate pruritus, which was alleviated after continuous usage. No severe adverse events occurred during the trial.
The data support the efficacy of combination topical rapamycin-calcitriol gel for reducing erythema, papule elevation, and overall facial angiofibroma severity in patients with TSC, the investigators suggest. As a study limitation, investigators noted the lack of a placebo treatment arm; further study is necessary to confirm the effects of rapamycin-calcitriol therapy. Yet, results support topical rapamycin-calcitriol treatment as a safe and effective option for patients with TSC-related FAs.
Chen PL, Hong JB, Shen LJ, Chen YT, Wang SJ, Liao YH. The efficacy and safety of topical rapamycin–calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double-blind, randomized clinical trial [published online February 16, 2020]. Br J Dermatol. doi: 10.1111/bjd.18949