title: Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results.
abstract: BACKGROUND
  Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery.
  
  
  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.
authors.forename: Brian
authors.initials: B
authors.lastname: Berman
authors.forename: Gary
authors.initials: G
authors.lastname: Goldenberg
authors.forename: C William
authors.initials: CW
authors.lastname: Hanke
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tyring
authors.forename: Wm Philip
authors.initials: WP
authors.lastname: Werschler
authors.forename: Kim Mark
authors.initials: KM
authors.lastname: Knudsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Larsson
authors.forename: Neil
authors.initials: N
authors.lastname: Swanson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003131:Combined Modality Therapy; D003452:Cryosurgery / Q000379:methods; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004224:Diterpenes / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005782:Gels; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged
chemical_list: C486592:3-ingenyl angelate; D003879:Dermatologic Agents; D004224:Diterpenes; D005782:Gels