Efficacy and Safety of Ingenol Mebutate 0.015% Gel After Cryosurgery of Actinic Keratosis: 12-Month Results
June 2014 | Volume 13 | Issue 6 | Original Article | 741 | Copyright © June 2014
Brian Berman MD PhD,a Gary Goldenberg MD,b C. William Hanke MD,c Stephen K. Tyring MD PhD,d
Wm Philip Werschler MD,e Kim Mark Knudsen PhD,f Thomas Larsson Dr Med Sci,g and Neil Swanson MDh
aDepartment of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, USA
bDepartment of Dermatology, Mount Sinai School of Medicine, New York, NY, USA
cDermatologic Surgery, Laser and Skin Surgery Center of Indiana, Carmel, IN, USA
dDepartments of Microbiology and Immunology, Dermatology and Internal Medicine, University of Texas Health Science Center, Houston, TX, USA
eDepartment of Medicine/Dermatology, University of Washington School of Medicine, Seattle, WA, USA
fBiostatistics and Data Management, LEO Pharma A/S, Ballerup, Denmark
gCentre of Excellence Scientific Affairs, LEO Pharma A/S, Ballerup, Denmark
hDepartment of Dermatology, Oregon Health and Science University, Portland, OR, USA
METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months.
RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P=.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P=.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment.
CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.
J Drugs Dermatol. 2014;13(6):741-747.