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

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