Assessment of Efficacy and Irritation of Ingenol Mebutate Gel 0.015% Used With or Without Dimethicone Lotion for Treatment of Actinic Keratosis on the Face
May 2017 | Volume 16 | Issue 5 | Original Article | 432 | Copyright © 2017
Shelbi C. Jim On MD, Peter W. Hashim MD, John K. Nia MD, and Mark G. Lebwohl MD
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
Background: Ingenol mebutate gel 0.015% provides high clearance rates for actinic keratosis (AK) on the face and scalp but causes transient local skin responses (LSRs).
Objective: This study sought to determine whether the application of 1% dimethicone would decrease ingenol mebutate–associated LSRs and/or affect efficacy during the treatment of multiple AKs on the face.
Methods: Ingenol mebutate gel 0.015% was applied for 3 days to two 25 cm2 areas, each containing 3 to 8 AKs on the face of each subject, followed by application of 1% dimethicone lotion in an investigator-blinded manner to one randomly selected AK-containing area until LSRs were no longer present.
Results: In total, 20 subjects were enrolled and completed the study. Topical 1% dimethicone lotion applied during and after treatment of facial AK with ingenol mebutate gel 0.015% reduced mean total LSR scores at days 8 and 15 compared with ingenol mebutate gel only, although the difference was not statistically significant. Efficacy was equivalent between the two treatment arms.
Limitations: The study evaluated a relatively small number of subjects, all of whom were white.
Conclusions: The application of 1% dimethicone following ingenol mebutate gel 0.015% produced a trend toward lower severity of some LSRs, with no difference in efficacy.
J Drugs Dermatol. 2017;16(5):432-436.
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Ingenol mebutate gel 0.015% provides high clearance rates for actinic keratosis (AK) on the face and scalp1 but causes transient local skin responses (LSRs): erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration.1-3 These six LSRs may be accompanied by treatment-associated adverse events (AEs) including, but not limited to, irritation, pain, and pruritus,1 which can be disturbing to patients. The development of LSRs following topical application of ingenol mebutate gel probably results from its mechanism of action, which appears to include rapid lesion necrosis followed by a lesion-specific immune response4 mediated through the PKCδ/MEK/ERK pathway and the downstream induction of IL1R2 and IL13RA2 expression.5 The precise roles of these pathways in clearance of AK by ingenol mebutate treatment are unknown.5 Although the course of therapy for facial AK with ingenol mebutate gel is only 3 consecutive days,6 and LSRs accompanying application of ingenol mebutate gel resolve rapidly without sequelae,1-3 there has been interest in reducing the intensity of LSRs without compromising efficacy.7 Currently, there are no clinical studies evaluating emollients with ingenol mebutate gel that demonstrate decreased irritation and inflammation with more rapid resolution of LSRs. A randomized controlled study of topical clobetasol propionate applied twice daily for 4 consecutive days following treatment of facial AKs with ingenol mebutate gel for 3 consecutive days did not alleviate LSRs or affect efficacy.7Dimethicone, a mixture of polydimethylsiloxanes and silicon dioxide (sometimes called simethicone), is a common ingredient in topical agents, such as emollient lotions used for the relief of irritation from inflammatory dermatoses.8-12 It is a hypoallergenic, non-comedogenic, and non-acnegenic agent that improves the integrity of the protective epidermal barrier and thereby inhibits transepidermal water loss.12 An investigator-initiated study of topical ingenol mebutate gel 0.015% was conducted to determine whether the addition of 1% dimethicone would decrease ingenol mebutate–associated LSRs and/or affect efficacy during and after treatment of multiple AKs on the face.
Study designThis was a single-center, investigator-initiated, Phase 1 study (ClinicalTrials.gov identifier: NCT02411851).13 The study protocol was approved by and received favorable opinion from the study site’s Institutional Review Board, and all subjects provided signed informed consent prior to participation. Blinded physician assessment was used to determine whether