Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.
BACKGROUND
There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis.


OBJECTIVE
Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis.


METHODS
Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period.


RESULTS
All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring.


CONCLUSIONS
Local skin responses may have suggested active treatment to investigators.


CONCLUSIONS
Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.
Anderson
Lawrence
L
Dermatology Associates of Tyler, Tyler, Texas, USA. LawrenceA@dermatologytyler.com
Schmieder
George J
GJ
Werschler
W Philip
WP
Tschen
Eduardo H
EH
Ling
Mark R
MR
Stough
Dow B
DB
Katsamas
Janelle
J
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004224:Diterpenes / Q000008:administration & dosage*; D004311:Double-Blind Method; D028481:Euphorbia; D005782:Gels; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy*; D008875:Middle Aged; D014677:Pharmaceutical Vehicles; D010936:Plant Extracts / Q000008:administration & dosage; D016896:Treatment Outcome
C486592:3-ingenyl angelate; D004224:Diterpenes; D005782:Gels; D014677:Pharmaceutical Vehicles; D010936:Plant Extracts