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Ingenol Mebutate for Actinic Keratoses

A short course of this plant-based agent significantly improved AK clearance.

Preliminary pilot studies (see JW Dermatol Feb 27 2009) indicated that ingenol mebutate might be effective for treating actinic keratoses (AKs). In this randomized, double-blind, vehicle-controlled, sequential-cohort, dose-finding study funded by the manufacturer, researchers compared three doses of ingenol mebutate (IM) gel and vehicle alone for nonfacial AKs. They randomized 222 subjects to receive: once-daily IM 0.025% gel applied for 3 days; once-daily IM 0.05% for 3 days; once-daily vehicle followed by 2 days of IM 0.05%; or vehicle applied for 3 days. Participants were followed for 57 days from initial application. Only two subjects dropped out.

All three active-treatment regimens cleared AKs significantly more effectively than vehicle alone. The percentage of patients with partial clearance (75% of baseline AKs cleared) ranged from 56% in the 0.025% group to 75% in the 3-day 0.05% group. The percentage of patients with complete clearance of all baseline AKs ranged from 42% in the 0.025% group to 58% in the 3-day 0.05% group. Complete clearance (no visible AKs, baseline or emergent) ranged from 40% of patients in the 0.025% group to 54% in the 3-day 0.05% group. Redness, flaking, and scaling were experienced for more than 2 weeks by almost all active-treatment recipients; these reactions were mild or moderate in 97% on day 8, mild in 70% by day 15, and absent in 72% by day 57.

Comment: Ingenol mebutate, derived from the plant Euphorbia peplus, acts on AKs by causing cellular necrosis and various immunomodulatory mechanisms in the skin. The AK clearance rate reported here is in line with the reported efficacy of 5-fluorouracil and imiquimod. The 3-day course is a great advantage over the 2 to 16 weeks needed with other topical treatments, which should greatly increase patient compliance. However, the IM-related downtime is quite similar to downtime with 5-fluorouracil treatment, which might hinder acceptance.

— George J. Hruza, MD

Published in Journal Watch Dermatology June 26, 2009

Citation(s):

Anderson L et al. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol 2009 Jun; 60:934.

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