Journal of Clinical and Aesthetic Dermatology

DEC 2017

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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26 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY December 2017 • Volume 10 • Number 12 O R I G I N A L R E S E A R C H two trials evaluating the application of ingenol mebutate gel on the face and scalp, Lebwohl et al 10 reported a mean percent reduction of 77.7 percent for the face (both trials) and 55 percent and 50 percent for the scalp, which compares favorably with results in the present trial (face/ chest, 78.9%; scalp, 76.3%). The different doses selected in this trial were determined in Phase I/II dose-finding trials, 13,14 and were partly based upon findings of the pivotal ingenol mebutate trials. 10 Lebwohl et al 10 evaluated one dose concentration to treat both the face and scalp and reported lower efficacy on the scalp. Similar findings for reduced efficacy on the scalp have also been reported in trials evaluating imiquimod. 20 Accordingly, the dose evaluated in the present trial has been optimized specifically for treatment on the scalp, which is more difficult to treat. Disparities in efficacy between different regions of skin may relate to differences in absorption and thus warrant optimized dosing concentrations. Limitations. It should be noted that the safety and efficacy data from this trial should be interpreted with caution, as the trial was open- label, potentially introducing patient and/or investigator bias. An additional consideration is that LSRs following ingenol disoxate application on the first day of treatment could have affected how patients self-applied treatment on the two subsequent days, potentially avoiding certain parts of the treatment area, or applying smaller amounts of gel. CONCLUSION In conclusion, ingenol disoxate, when administered once daily over three consecutive days in patients with AK, demonstrated similar findings as previous trials with respect to AE and LSR profiles. It might be an effective field treatment as evidenced by the reduction in AK count and the complete and partial clearance (AKCLEAR 100 and AKCLEAR 75) results. These data support the use of ingenol disoxate for the field treatment of AK. Phase III assessments of ingenol disoxate at the concentrations reported in this trial are being pursued. ACKNOWLEDGMENTS The study was funded by LEO Pharma. Medical writing services were provided by Louise Prince, PhD, and Patrick Griffin, MSc, of iMed Comms, an Ashfield Company, part of UDG Healthcare plc, and funded by LEO Pharma in accordance with Good Publication Practice guidelines. The authors thank the investigators who participated in this study. REFERENCES 1. Einspahr JG, Stratton SP, Bowden GT, Alberts DS. Chemoprevention of human skin cancer. Crit Rev Oncol Hematol. 2002;41(3):269–285. 2. Berman B, Amini S. Pharmacotherapy of actinic keratosis: an update. Expert Opin Pharmacother. 2012;13(13):1847–1871. 3. Alam M. Actinic keratoses: prevalence, pathogenesis, presentation, and prevention. Adv Stud Med. 2006;6(8A):785–790 4. Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994;131(4):455–464. 5. Malvehy J. A new vision of actinic keratosis beyond visible clinical lesions. J Eur Acad Dermatol Venereol. 2015;29(Suppl 1):3–8. 6. Fu W, Cockerell CJ. The actinic (solar) keratosis: a 21st-century perspective. Arch Dermatol. 2003;139(1):66–70. 7. Vatve M, Ortonne JP, Birch-Machin MA, Gupta G. Management of field change in actinic keratosis. Br J Dermatol. 2007;157(Suppl 2):21–24. 8. Fernandez-Figueras MT, Carrato C, Saenz X, et al. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol. 2015;29(5):991–997. 9. Heerfordt IM, Nissen CV, Poulsen T, et al. Thickness of actinic keratosis does not predict dysplasia severity or p53 expression. Sci Rep. 2016;6:33952. 10. Lebwohl M, Swanson N, Anderson LL, et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012;366(11):1010–1019. 11. Bertelsen M, Stahlhut M, Grue-Sorensen G, et al. Ingenol disoxate: a novel 4-isoxazolecarboxylate ester of ingenol with improved properties for treatment of actinic keratosis and other non- melanoma skin cancers. Dermatol Ther (Heidelb). 2016;6(4):599–626. 12. Sinnya S, Tan JM, Prow TW, et al. A randomised, Phase IIa exploratory trial to assess the safety and preliminary efficacy of LEO 43204 in patients with actinic keratosis. Br J Dermatol. 2015;174(2): 305–311. 13. Weiss J, Ulrich M, Bukhalo M, et al. A seamless Phase I/II dose-finding trial assessing ingenol disoxate (LEO 43204) for field treatment of actinic keratosis on the scalp. Br J Dermatol. 2017;176(6):1456–1464. 14. Bourcier M, Stein Gold L, Guenther L, et al. A dose finding trial with a novel ingenol derivative (ingenol disoxate; LEO 43204) for field treatment of actinic keratosis on full face or 250cm 2 on the chest. J Dermatolog Treat. 2017; 28(7):652–658. 15. Berman B, Tyring S, Nahm WK, et al. Three-day field treatment with ingenol disoxate (LEO 43204) for actinic keratosis: cosmetic outcomes and patient satisfaction from a phase 2 trial. J Clin Aesthet Dermatol. 2017;10(11):26–32. 16. Rosen R, Marmur E, Anderson L, et al. A new, objective, quantitative scale for measuring local skin responses following topical actinic keratosis therapy with ingenol mebutate. Dermatol Ther (Heidelb). 2014;4(2):207–219. 17. Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the treatment satisfaction questionnaire for medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12. 18. Ceilley RI, Jorizzo JL. Current issues in the management of actinic keratosis. J Am Acad Dermatol. 2013;68(1 Suppl 1):S28–S38. 19. Ulrich M, Lange-Asschenfeldt S, Skak K, et al. Biological effects of ingenol mebutate gel in moderate to severe actinic fields assessed by reflectance confocal microscopy: a phase I study. J Drugs Dermatol. 2016;15(10):1181–1189. 20. Swanson N, Smith CC, Kaur M, Goldenberg G. Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: two phase 3, multicenter, randomized, double-blind, placebo-controlled studies. J Drugs Dermatol. 2014;13(2):166–169. JCAD

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