Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis - 08/08/11
, George J. Schmieder, DO b, W. Philip Werschler, MD c, Eduardo H. Tschen, MD d, Mark R. Ling, MD, PhD e, Dow B. Stough, MD f, Janelle Katsamas g
Reprint requests: Lawrence Anderson, MD, FACP, 1367 Dominion Plaza, Tyler, TX 75703.Abstract |
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 ≤ .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.
Limitations |
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.
Le texte complet de cet article est disponible en PDF.Abbreviations used : AE, AK, 5-FU, GSR, LSR, SCC
Plan
| Funding sources: Peplin Ltd, for Clinical Research and as a member of the Scientific Advisory Committee. |
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| Disclosure: Dr Anderson was a clinical investigator, chairs a dose escalation committee on an unrelated clinical trial, and serves on an advisory board for Peplin Ltd. Ms Katsamas is an employee of Peplin Ltd. Dr Ling received a research grant for clinical studies from Graceway and Actavis. Dr Schmieder served as an investigator for Peplin, Genentech, Novum, and Astellas. Dr Werschler has served as an investigator for Peplin, Graceway, and Valent/ICN and as an investigator, speaker, consultant, and on an advisory board for Dermik. Drs Stough and Tschen report no conflicts of interest. |
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| A list of all clinical investigators participating in the study is found at the end of the article. |
Vol 60 - N° 6
P. 934-943 - juin 2009 Retour au numéro
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