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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24 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 DISCUSSION AK presents itself not only in visibly discrete AK lesions, but also subclinically in areas of field cancerization. Ingenol disoxate is a new ingenol derivative with improved stability characteristics and preserved or improved anti-tumor characteristics as compared with ingenol mebutate, including cell death mechanisms, activation of protein kinase C, and induction of local immune response. 11 This Phase II trial examined the safety and efficacy of ingenol disoxate following daily application of 0.018% gel on the full face/chest (approximately 250cm 2 ), 0.037% gel on the scalp (25–250cm 2 ), or 0.1% gel on the trunk/ extremities (approximately 250cm 2 ) over three consecutive days. Safety. The overall number of DLEs per treatment group was comparable with the incidence observed in previous dose-finding studies with once-daily dosing for two consecutive days. 13,14 The LSR profile of the ingenol disoxate regimen in this trial was comparable with those of previous dose-finding studies that evaluated a shorter two-day regimen; Weiss et al 13 and Bourcier et al 14 reported that, following ingenol disoxate application, LSR scores peaked on Day 3, rapidly declined, and reached or approached baseline levels by Week 4. Similarly, in the present trial, the mean composite LSR score peaked the day after the final application of ingenol disoxate (Day 4) and rapidly declined, reaching or approaching baseline levels by Week 4. The peak composite LSR scores in the present trial were slightly higher than those reported in the previous trials, in line with a longer duration of treatment; Weiss et al 13 observed mean LSR scores on Day 3 of 8.6 and 8.7 for ingenol disoxate gels at 0.037% and 0.05%, respectively; Bourcier et al 14 reported a mean composite LSR score on Day 3 for ingenol disoxate gel at 0.018%, 0.012%, and 0.006% of 8.6, 8.0, and 6.0, respectively. However, higher composite LSRs in this trial resolved over a similarly short time period to the previous trials, and did not affect adherence to treatment, as 97 percent of patients overall completed the three- day treatment regimen. 15 The most common LSRs across all treatment groups, in the previous trials evaluating ingenol disoxate, were erythema and flaking/ scaling. 13,14 In the present trial, erythema was the most common LSR reported by patients. In the majority of patients, the LSRs of swelling and vesiculation/pustulation resolved by Week 4 despite being relatively high on Day 4, suggesting these individual LSR components resolved quicker than the others. Erosion/ ulceration was the least dominant LSR and resolved in the majority of patients by Week 4. Three-day dosing with ingenol mebutate has also demonstrated similar safety findings. 10 When ingenol mebutate 0.015% gel was applied to the face and scalp, local skin reactions peaked on Day 4, with a mean maximum composite LSR score of 9.1. They then rapidly FIGURE 5. Reduction in actinic keratosis (AK) lesion count at Weeks 4 and 8. Excludes hyperkeratotic/hypertrophic lesions. FIGURE 6. Percentage of patients with complete clearance of actinic keratoses (AKCLEAR 100) at Weeks 4 and 8; excludes hyperkeratotic/hypertrophic lesions

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