High efficacy of red light photodynamic therapy with 10 % aminolevulinic acid gel irrespective of the extent of keratinocyte atypia in actinic keratosis - exploratory post-hoc analysis of three pivotal phase III trials

Background: Primary endpoints of clinical studies investigating treatments for actinic keratosis (AK) are mainly based on clinical evaluation, but a recent study showed that in AK, clinical classification according to Olsen and the extent of keratinocyte atypia do not necessarily correlate. The influence of the epidermal extent of atypia on treatment efficacy is usually not investigated and therefore remains largely unknown. Objective: To evaluate whether the extent of keratinocyte atypia influences efficacy of photodynamic therapy (PDT) when treating AK. Methods: We performed a post-hoc analysis of histological (keratinocyte intraepithelial neoplasia (KIN)), and clinical (Olsen) data of biopsied lesions of three pivotal studies evaluating PDT using 10 % aminolevulinic acid (ALA) gel or vehicle and narrow- or broad-spectrum red light lamps. Results: Overall, 514 biopsied lesions were considered. Clearance rates after red light PDT with 10 % ALA gel were comparable for KIN I-III (88.2 %, 92.0 % and 87.9 %) and Olsen I-II lesions for any given lamp type. Generally, clearance rates were higher using narrow- compared to broad-spectrum lamps. For both lamp types, the variation in clearance rates from KIN I-III was low. Clearance was lower with vehicle. Limitations: Varying lesion numbers in the subgroups and a remaining risk of bias due to the biopsies are potential limitations. Conclusion: Our results suggest that red light PDT with 10 % ALA gel is an effective treatment option for AK regardless of the extent of keratinocyte atypia.