A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex.

OBJECTIVE: This article assesses the efficacy, safety, pharmacology, and clinical applications of topical sirolimus 0.2% gel for the treatment of tuberous sclerosis complex (TSC)-associated facial angiofibromas. DATA SOURCES: A review of the literature was conducted using the Medline (PubMed) and EMBASE databases using the keywords topical sirolimus, rapamycin, Hyftor, and tuberous sclerosis. STUDY SELECTION AND DATA EXTRACTION: Articles written in English and relevant to the topic were included. DATA SYNTHESIS: In the phase 2 trial, the mean improvement factor, a composite measure of improved tumor size and redness, was achieved in all patient groups (P < 0.001) with significant responses among the adult and pediatric subgroups at week 12. There were no serious adverse events recorded. In the phase 3 trial, 60% of participants responded to treatment in the sirolimus group compared with 0% in the placebo group with different response rates between the adult and pediatric subgroups at week 12. Sirolimus gel had no serious adverse events, and dry skin was the most common adverse reaction. Patients who had completed the 12-week trials were then enrolled in a long-term trial; angiofibromas had response rates of 78.2% to 0.2% sirolimus gel. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Topical sirolimus 0.2% is a first-in-class, newly Food and Drug Administration (FDA)-approved, mammalian target of rapamycin (mTOR) inhibitor that is a promising and safe, noninvasive alternative to surgical procedures for TSC-associated angiofibromas. CONCLUSIONS: Topical sirolimus 0.2% gel is a moderately effective treatment for TSC-associated facial angiofibromas with an adequate safety profile.

1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses.

OBJECTIVE: Actinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration. DATA SOURCES: The PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri. DATA EXTRACTION: Phase 2 and phase 3 clinical trials were reviewed. DATA SYNTHESIS: In phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias. CONCLUSION: With a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.