Reduction in lesions from Lmax: a new concept for assessing efficacy of field-directed therapy for actinic keratosis. Results with imiquimod 3.75%

Background: Current parameters for assessing the efficacy of actinic keratosis (AK) treatments compare clinical lesions at the start and end of a study. However, the sun-exposed field also contains subclinical lesions which may become detectable during treatment. Lmax, the maximum lesion count during treatment, is a new concept to better assess the efficacy of field-directed AK therapies. Measuring efficacy using the reduction in lesions from Lmax includes for the first time the clearance of both subclinical and clinical lesions. Objectives: To evaluate the reduction of lesions from Lmax to study end and compare the results with traditional efficacy endpoints using imiquimod 3.75% (IQ3.75%) as an example of field-directed AK therapy. Materials & Methods: Pooled analysis of data from two 14-week, vehicle-controlled, double-blind studies of IQ3.75%. Results: With IQ3.75%, the median number of lesions increased from 10 at baseline to an Lmax of 22. The median absolute reduction in lesions to study end was 18 from Lmax versus 7 from baseline. The median percentage reduction in AK lesions to study end was 92.2% from Lmax compared with 81.8% from baseline. Conclusions: The reduction in lesion count from Lmax is a novel efficacy parameter that should become the new way of evaluating field-directed AK therapies since it enables their efficacy against both clinical and subclinical lesions to be accurately determined. Together, the Lmax concept and IQ3.75% represent a new approach for the management of AK across a large sun-exposed field.