A Randomized, Double-blinded, Placebo-controlled, Multicenter, Efficacy and Safety Study of 3.75% Imiquimod Cream Following Cryosurgery for the Treatment of Actinic Keratoses

Objective: Evaluate cryosurgery followed by 3.75% imiquimod cream to treat actinic keratoses (AK). Methods: Adults with ≥10 AKs on the face underwent cryosurgery of five to 14 lesions. Subjects with ≥5 lesions remaining were randomized to 3.75% imiquimod or placebo cream applied to the entire face daily for two two-week cycles. Efficacy was assessed through week 26. Results: For the cryosurgery/3.75% imiquimod (n=126) and cryosurgery/placebo (n=121) groups, respectively, median total AK reductions were 86.5 and 50 percent, and proportions of subjects with complete clearance were 30.2 and 3.3 percent (P<0.0001, both). Analyzing cryosurgery-treated lesions only, median reductions were 100 and 80 percent (P=0.0008), and subject complete clearance rates were 59.5% and 29.8% (P<0.001), respectively. Only one subject discontinued for a treatment-related adverse event (cryosurgery/3.75% imiquimod group). Limitations: Cryosurgery was performed per usual study center practice and not standardized. Conclusion: A short, cyclical treatment course of field-directed daily 3.75% imiquimod cream following lesion-directed cryosurgery was well tolerated and provided additional therapeutic benefits to cryosurgery alone.