Effectivity of a novel betulin-based oleogel in the treatment of actinic keratoses. A prospective, randomised, comparative pilot study with histology

Actinic keratoses (AK) represent an obligatory precancerous skin condition and require therapy at any rate. Betulin-based oleogel prepared from a standardised birch bark extract represents a new topical agent with anti-inflammatory and anti-tumor potential. In the present study we have assessed the efficacy of topical betulin-based oleogel in the treatment of AK. In the prospective, randomised, monocentric phase 2a study 45 patients with ≤10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin-based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin-based oleogel. Treatment response was clinically assessed after three months. The clinical response was graded into therapy responders (≥75% clearing of the lesions) and non-responders (<75% clearing). Additionally, punch biopsies were taken on a voluntary basis from preassigned reference lesions before and at the end of treatment. Biopsy specimens were examined using routine staining. Therapy with betulin-based oleogel was well tolerated by the patients both as a monotherapy and in combination with cryotherapy. Three patients discontinued therapy because of personal reasons. After three months, clearing of more than 75% of the lesions was seen in 85% of the patients treated with betulin-based oleogel (n=14), 93% of the patients treated with cryotherapy (n=14) and 80% of the patients treated with the combination therapy (n=14). The skin tolerance of the betulin-based oleogel was excellent. Histological analysis of biopsies taken after treatment (n=8) confirmed the results of the clinical grading in all study arms. Betulin-based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However, the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.