Relationship between severity of the local skin reactions and the rate of local skin reaction resolution in patients treated with ingenol mebutate gel

Abstract

BackgroundIngenol mebutate gel is a topical field treatment for actinic keratosis (AK). The treatment elicits application-site reactions in most patients. This analysis evaluated the relationship between the severity of reactions and the speed of their resolution.MethodsPatients in Phase III studies were treated for AKs on the face (n=218), scalp (n=56), and trunk and extremities (n=209). All of the patients were treated with either ingenol mebutate gel 0.015% once daily for three consecutive days (face/scalp) or ingenol mebutate gel 0.05% once daily for two consecutive days (trunk/extremities). Local skin reactions (LSRs) were assessed on a 5-point scale from 0 to 4 in six categories, yielding composite scores in the range of 0 to 24.ResultsThe composite LSR score on the day after the last application of ingenol mebutate gel was an important predictor of the speed of resolution of LSRs. The rate of resolution was greatest for AKs treated on the face, followed by the scalp, and then the trunk and extremities. All patients were expected to have minimal LSR scores for the face and scalp at 2 weeks, and for the trunk and extremities at 4 weeks.ConclusionThe absolute reduction in LSR scores was proportional to the composite LSR score on the day after the last application of ingenol mebutate gel treatment. The rate of resolution for LSRs was dependent on the anatomic site treated as well as the day 4 composite score.

Ingenol mebutate for the treatment of actinic keratosis: effectiveness and safety in 246 patients treated in real-life clinical practice

“…Due to its mechanism of action, the development of specific local skin responses (LSRs) such as erythema, ulcerations, and crusting (10) has been reported after the topical treatment with IMG. Evidence suggests that these LSRs tend to spontaneously resolve within 2-4 weeks after treatment, which is correlated with the initial severity shown within the affected skin field (11).…”

Prevalence, Discontinuation Rate, and Risk Factors for Severe Local Site Reactions with Topical Field Treatment Options for Actinic Keratosis of the Face and Scalp

“…The prevalence of severe LSRs among various topical field treatment options is summarized in Table 1 [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28].…”

“…Each of six LSR parameters—erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation, and erosion/ulceration is graded from 0 to 4, giving a maximum composite score of 24 [15,29]. Jim On et al [16] reported data of two multicenter, randomized, parallel-group, double-blind, vehicle-controlled studies, involving face and scalp and classified patients with a composite score of 12 or higher as having a severe LSR. Thus, their reported prevalence of severe LSRs at day 4 was 24.5%.…”