Ingenol mebutate gel was significantly more effective than vehicle alone.

Actinic keratoses (AKs) are extremely common lesions that affect nearly 40 million individuals in the United States alone and many more worldwide. Conversion rates of AKs to nonmelanoma skin cancers are estimated to range from 6% to 10% over a 10-year period. Field therapy of the entire area of sun-damaged skin is frequently performed in patients with extensive AKs. Although highly effective, most forms of field therapy require prolonged treatment and cause a protracted irritant reaction, sometimes quite strong. Ingenol mebutate, the active ingredient of sap of Euphorbia peplus, has been in long use in Australia for many skin conditions. These investigators conducted two manufacturer-supported trials of the safety and efficacy of a 0.015% concentrate of ingenol mebutate gel for AKs of the face and scalp in 547 patients with extensive actinic damage and multiple AKs.


Approximately half received ingenol mebutate gel and the others received vehicle applied daily for 3 days. At day 57, 42.2% of ingenol mebutate recipients were completely clear of AKs in the treated area, and the median reduction in the active treatment group was 83%. In the vehicle group, 3.7% had complete clearance and the median reduction in lesion count was 0%. These differences were highly significant. In a follow-up study in 108 patients with complete clearance, only 13% of the baseline number of lesions were present 12 months later. Nearly all ingenol mebutate recipients developed an irritant reaction, which resolved by 2 weeks. Little if any treatment-associated dyspigmentation or scarring was noted. Only 3 of the 277 ingenol mebutate recipients discontinued treatment early. Two other studies that evaluated the use of ingenol mebutate gel 0.05% on the trunk and extremities yielded nearly identical results; the overall degree of irritation was milder but persisted somewhat longer.


Citation(s):

Lebwohl M et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med 2012 Mar 15; 366:1010.