Efficacy and Safety of Imiquimod 3.75% from Lmax in Actinic Keratosis According to Fitzpatrick Skin Type

March 2016 | Volume 15 | Issue 3 | Original Article | 285 | Copyright © March 2016

Agustin Alomar MD,a Eggert Stockfleth MD,b Thomas Dirschka MD,c Girish Gupta FRCP,d Selim Aractingi MD PhD,e Rada Dakovic PhD,f and Ketty Peris MDg

aDepartment of Dermatology, Institut Universitari Quiron Dexeus, Barcelona, Spain
bKlinik für Dermatologie, Venerologie und Allergologie, St. Josef-Hospital, Ruhr-Universität Bochum, Bochum, Germany
cDermatological Practice Centre, Wuppertal, and Faculty of Health, University Witten-Herdecke, Germany
dDepartment of Dermatology, Monklands Hospital, Airdrie, Lanarkshire, UK
eService de Dermatologie Allergologie, Hôpital Cochin, Paris and Université Paris 5 Descartes, Paris, France
fMeda Pharma GmbH & Co. KG, Bad Homburg, Germany
gDepartment of Dermatology, Catholic University of Rome, Rome, Italy

Abstract
BACKGROUND: Imiquimod 3.75% is an effective actinic keratosis (AK) treatment that detects and clears clinical and subclinical lesions across an entire sun-exposed field such as the full face or balding scalp.
OBJECTIVE: To determine the efficacy and safety of imiquimod 3.75% according to patients’ Fitzpatrick skin type.
METHODS: Data were pooled from two identical 14-week, double-blind studies. Patients were randomized to imiquimod 3.75% or placebo and applied study medication to the full face or balding scalp each day for 2 two-week treatment cycles separated by a two-week treatment-free interval. End of study (EOS) was eight weeks after the last treatment application. Patients were subgrouped according to whether they had Fitzpatrick skin types I or II (FST I/II), or types III or IV (FST III/IV). Efficacy was analyzed using the reduction in lesions from Lmax (maximum lesion count during treatment) to EOS. This assesses whether clinical lesions, and subclinical lesions which become detectable during treatment, are cleared. Safety was assessed by monitoring local skin reactions.
RESULTS: In total, 173 patients with FST I/II and 142 with FST III/IV were included. The median percentage reductions in lesions from Lmax to EOS were similar in patients treated with imiquimod 3.75% with FST I/II and FST III/IV (94.2% and 89.7%, respectively) as were the median absolute reductions in lesions from Lmax to EOS (19.0 and 17.0, respectively). These reductions were significantly greater with imiquimod 3.75% versus placebo in the two respective FST subgroups (P<0.0001). The frequency of local skin reactions was similar in the two imiquimod 3.75% FST subgroups.
CONCLUSIONS: Imiquimod 3.75% is well tolerated and effective at clearing clinical and subclinical lesions across large areas of sun-exposed skin in patients with FST I–IV, and so can be considered for AK patients with any of these skin types.

J Drugs Dermatol. 2016;15(3):285-289.

INTRODUCTION

Actinic keratoses (AK) are part of a disease continuum that can progress from initial keratinocyte dysplasia to invasive squamous cell carcinoma (SCC).1 Ultraviolet light affects the entire sun-exposed area of skin resulting in field cancerization in which subclinical or invisible lesions, clinical or visible lesions, and invasive SCC may co-exist.2 Given that it is not possible to predict which lesions will progress to invasive SCC, experts recommend that all lesions across the entire sun-exposed field should be treated.3
Imiquimod 3.75% is an effective treatment for AK. A pooled analysis of data from two identical, 14-week, placebo-controlled, double-blind studies demonstrated that imiquimod 3.75% detects and clears 92% of clinical and subclinical lesions across an entire sun-exposed field such as the full face or balding scalp.4 Similar efficacy is observed in patients with low and high numbers of clinical AK lesions, with 91.5% of clinical and subclinical lesions being cleared in patients with ≤10 baseline lesions and 93.0% being cleared in those with >10 baseline lesions.5 The lesion clearance with imiquimod 3.75% is also maintained over the long-term.6,7
Although several studies have shown that Fitzpatrick skin type affects the likelihood of developing AK with a greater risk in patients with lighter skin types,8-10 so far no studies have evaluated whether the response to AK treatment is also affected by Fitzpatrick skin type. Therefore, the aim of this post-hoc analysis of the pivotal studies of imiquimod 3.75% was to determine its efficacy according to patients’ Fitzpatrick skin type. Efficacy was analyzed using the reduction in lesions from Lmax (the maximum lesion count during treatment) since this parameter assesses the ability of AK treatments to clear both clinical