Sequential topical field-directed therapy with ingenol mebutate gel for 3 days following cryosurgery significantly improves the outcomes in patients with actinic keratosis, a phase III randomized study showed.
Enrolled patients had four to eight clinically typical lesions on the face or scalp and received cryosurgery to all visible lesions followed by once-daily treatment of ingenol mebutate 0.015% gel or vehicle gel for 3 consecutive days at home, after 3 weeks of healing.
At 11 weeks, patients who received treatment with ingenol mebutate gel (n = 167) postsurgery, saw higher rates of complete clearance of lesions, compared with patients receiving the vehicle alone after surgery (n = 162) (60.5% vs. 49.4%; P=.04), reported Dr. Stephen K. Tyring and his associates this month (J. Drugs Dermatol. 2014;13:154-60).
In longer-term follow-up at 12 months, ingenol mebutate gel continued to show significantly improved complete clearance rates, compared with vehicle gel (30.5% vs. 18.5%; P = .01), Dr. Tyring reported at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
The mean percentage reduction of lesions at 12 months was significantly higher with ingenol mebutate for all lesions (59.5% vs 44.4%, P=0.004) and 38.9% of patients receiving ingenol mebutate saw emergence of new lesions on the treatment area between baseline lesions, compared with 51.9% of patients in the vehicle group (P=0.01), he said.
The complete clearance at 11 weeks (60.5% vs 49.4%; P=0.04) with a relative complete actinic keratosis clearance ratio of 1.22 (1.01-1.49) increased to 1.67 (1.12-2.50) at 12 months in the treatment group vs vehicle, following cryosurgery, noted Dr. Tyring of University of Texas Health Science Center at Houston.
The most frequently reported adverse events in the treatment group were application site discomfort and pruritus. Over the 12-month follow-up, 16 patients in the ingenol mebutate group reported one or more adverse events, as did 6 in the vehicle group. These events, however, were minor and well tolerated, said Dr. Tyring.
Ingenol mebutate gel was approved by the Food and Drug Administration in 2012 to treat actinic keratosis. Its advantage over other topical field agents such as 5-fluorouracil, imiquimod, and diclofenac is its short treatment period of 2-3 days, depending on the treatment area. This reduces the likelihood of patients discontinuing because of inflammation, burning, or other adverse events, Dr. Tyring noted.
Ingenol mebutate significantly enhanced the efficacy of cryosurgery, a difference that comes "both from enhancing the effect of cryosurgery with ingenol mebutate on the visible baseline lesions, and from a field treatment effect of ingenol mebutate on subclinical lesions not visible at baseline," Dr. Tyring said.
Dr. Tyring disclosed financial relationships with Astellas, Epiphany, Catalyst, GlaxoSmithKline, Novartis, 3M, VaxGen, Merck, BMS, Amgen, Biogen, Genentech, Corixa, Abbott, Graceway, Leo, and Warner Chilcott. SDEF and this news organization are owned by the same parent company.