Imiquimod 2.5% and 3.75% for the Treatment of Actinic Keratoses: Results of Two Placebo-controlled Studies of Daily Application to the Face and Balding Scalp for Two 3-week Cycles

Background: Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2) area of skin.

Objective: We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp.

Methods: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment.

Results: In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively.

Limitations: Local effects of imiquimod, including erythema, may have led to investigator and subject bias.

Conclusions: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.