Imiquimod 2.5% and 3.75% for the Treatment of Actinic Keratoses: Two Phase 3,Multicenter, Randomized, Double-Blind, Placebo-Controlled Studies
February 2014 | Volume 13 | Issue 2 | Original Article | 166 | Copyright © February 2014
Neil Swanson MD,a Christina Cognata Smith PharmD,b Mandeep Kaur MD,b and Gary Goldenberg MDc
aDepartment of Dermatology, Oregon Health and Science University, Portland, OR
bFormerly with Medicis (A division of Valeant Pharmaceuticals) Scottsdale, AZ
cDepartment of Dermatology, Mount Sinai School of Medicine, New York, NY
METHODS: In two identical multicenter, randomized, double-blind, placebo controlled studies. Adult subjects with 5 to 20 visible lesions, or palpable AKs in an area that exceeded 25cm2 on either the face or balding scalp were randomized to imiquimod 3.75%, 2.5% or vehicle cream (1:1:1) applied once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed 8 weeks posttreatment (End of Study Visit [EOS]). Primary efficacy was rate of complete clearance of AK lesions. Secondary efficacy endpoints were rate of partial clearance at EOS (≥ 75% reduction in number of AK lesions compared to baseline) and median percent decrease from baseline lesion count. Safety assessments included visual assessment of local skin reactions (LSRs), number and duration of study treatment rest periods required due to intolerant LSRs, adverse events (AEs) and clinical laboratory tests.
RESULTS: Overall 479 patients were randomized to imiquimod 3.75%, 2.5%, or vehicle. Complete clearance rates were 35.6%, 30.6%, and 6.3% respectively (both P<.001 versus vehicle). The difference in complete clearance rates (imiquimod minus vehicle) was 29.3% and 24.3%, respectively. Partial clearance rates were 59.4%, 48.1%, and 22.6% respectively (both P<.001 versus vehicle). Median % reductions in AK lesions were 81.8%, 71.8%, and 25.0% respectively (P<.001 versus vehicle). All primary and secondary efficacy endpoints were greater in Study 1. Photodamage in the treatment area was 'much improved' with imiquimod 3.75%. Both active creams were well tolerated with few treatment-related discontinuations.
CONCLUSIONS: In two well-controlled Phase 3 studies, both imiquimod 3.75% and 2.5% creams were more effective than vehicle and well tolerated when administered daily as a 2-week on/off/on regimen to treat AK. Reduction in AK lesions was comparable to that reported with imiquimod 5% with fewer local AEs.
J Drugs Dermatol. 2014;13(2):166-169.