Investigational Gel Quickly Clears Actinic Keratosis

A new study reports that more than 40% of patients had complete clearance of actinic keratosis (AK) during treatment with ingenol mebutate gel, a macrocyclic diterpene ester derived from the sap of the Euphorbia peplus (Milkweed) plant.

Researchers at the Oregon Health and Science University (OHSU; Portland, USA) conducted four multicenter, double-blind studies that randomly assigned patients with AK on the face, scalp, or on the trunk or extremities to receive ingenol mebutate (0.015% for face and scalp and 0.05% for trunk and extremities) or placebo gel, self-applied to a 25 cm2 contiguous field once daily for three consecutive days (for lesions on the face or scalp), or for two consecutive days for the trunk or extremities. Safety assessments occurred at prespecified intervals from three to 57 days, and efficacy was assessed on day 57; local reactions were quantitatively measured.

The results showed that in the pooled analysis of the two trials involving the face and scalp, the rate of complete clearance was higher with ingenol mebutate (42.2%) than with placebo (3.7%). Local reactions peaked at day 4, rapidly decreased by day 8, and continued to decrease, approaching baseline scores by day 29. In a pooled analysis of the two trials involving the trunk and extremities, the rate of complete clearance was also higher with ingenol mebutate (34.1%) than with placebo (4.7%). Local skin reactions peaked between days 3 and 8 and declined rapidly, approaching baseline by day 29. Adverse events were generally mild to moderate in intensity and resolved without sequelae. The study was published on March 15, 2012, in the New England Journal of Medicine (NEJM).

“On the face or scalp, where irritation is most noticeable, the peak local-skin-response score was recorded at the day four visit; the score declined rapidly thereafter, and local reactions were almost resolved by the day 15 visit,” concluded lead author Mark Lebwohl, MD, and colleagues. “The short duration of treatment may result in very high adherence to the therapy, contributing to the effectiveness of ingenol mebutate.”

AK is a small, rough, raised area found on skin that has been in the sun for a long period of time, and is a common precursor to sun-related squamous-cell carcinoma. It is usually found on the face, scalp, back of the hands, chest, or other sun-exposed areas, and it begins as a gray, pink, red, or skin colored flat and scaly area, often with a white or yellow crusty "scale.” This later develops into a hard and wart-like or gritty rough surface. Cryosurgery and other ablative therapies effectively eliminate precancerous AK lesions, but the treatment can cause scarring and recurrence is common.

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Oregon Health and Science University