Safety and Efficacy of Multiple 16-week Courses of Topical Imiquimod for the Treatment of Large Areas of Skin Involved with Actinic Keratoses.

OBJECTIVE: Safety of multiple 16-week courses of imiquimod applied to large areas (>25 cm(2)) of skin with actinic keratoses.

DESIGN: Subjects applied 1 to 6 packets two times per week for 16 weeks; if actinic keratoses were persistent at two months post-treatment, up to two additional courses could be administered within the 18-month study period.

SETTING: Multicenter, outpatient.

PARTICIPANTS: Adults with >/=4 actinic keratoses on the head, torso, and/or extremities.

MEASUREMENTS: Treatment discontinuations, adverse events, lesion counts.

RESULTS: Safety analyses included 551 subjects. At baseline, mean overall treatment area was 625+/-1114cm(2). Overall, the mean days on study was 467+/-157, and the mean exposure 215+/-133 packets with 155, 150, and 250 subjects receiving 1, 2, or 3 treatment courses, respectively. Of the 155 subjects (28.1%) who did not complete the study, 20 (3.6%) and 9 (1.6%) were discontinued for adverse events and local skin reactions, respectively. Adverse events related to study drug were reported by 40.5 percent of subjects. The local skin reactions rated as severe reported by the most subjects were erythema (31.4%), flaking/scaling/drying (23.8%), and scabbing/crusting (22.0%). For 525 subjects with analyzable lesion data, the mean baseline lesion count was 45.5+/-2.4. Overall reduction in target lesion count was 80.2 percent (p<0.0001, 95% CI 77.2-83.3%), with overall complete clearance rate of 36.4 percent and partial clearance rate (>/=75% reduction) of 68.6 percent.

CONCLUSION: Multiple 16-week courses of imiquimod to treat actinic keratoses were well tolerated and significantly decreased lesions in subjects with extensive actinic keratoses.