Imiquimod

Stockfleth E, Meyer T, Benninghoff B, et al. A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses. Arch Dermatol 2002; 138:1498-1502.

* PRACTICE RECOMMENDATIONS

Imiquimod 5% cream, applied 3 times per week for 12 weeks, is effective for treatment of actinic keratosis. Severe erythema and other local reactions occurred in almost everyone receiving treatment, due to imiquimod's immune system--modulating effects.

The 25 patients in the treatment group tolerated these adverse effects well. Despite these effects, imiquimod can be used as an alternative to traditional cryotherapy for the treatment of actinic keratosis among selected, motivated patients.

* BACKGROUND

Actinic keratosis is a precancerous skin lesion commonly found on areas frequently exposed to the sun. Among aging Americans, these lesions are regularly identified and treated in the clinical setting with cryotherapy. This manufacturer-sponsored study evaluated the efficacy and safety of 5% imiquimod (Aldara) cream for the treatment of actinic keratosis.

* POPULATION STUDIED

Patients were selected from a dermatology practice in Germany. Of 52 patients screened, 36 men and women with histopathologically diagnosed actinic keratosis were enrolled. Study patients were ages 45 to 85 years. Each patient had 3 to 10 actinic keratosis lesions on the scalp, forehead, dorsal forearm, neck, or dorsal hand.

Patients were excluded if they were receiving immune modulators (including imiquimod) or were recently treated for a viral or bacterial infection. Patients with cardiovascular, hematologic, hepatic, neurologic, renal, endocrine, vascular, or gastrointestinal conditions were also excluded.

* STUDY DESIGN AND VALIDITY

The study was a randomized, double-blind, vehicle-controlled clinical trial. Histopathologic diagnosis was confirmed in 36 enrollees. The imiquimod group had 25 patients, while the vehicle cream control group had 11 patients. Masking of patients, physicians, and outcome assessors was appropriate, as was allocation concealment.

Each patient applied the cream 3 times per week for 12 weeks. The cream was left on for 8 hours at a time. Patients were assessed at 2, 3, 6, 9, 12, and 14 weeks. Enrollees were also evaluated 1 year after treatment. Among patients with severe reactions, application was reduced to 1 or 2 times per week. Rest periods were also allowed.

Analysis was by per-protocol basis rather than by intention-to-treat, so only 36 of 52 patients were included in the final results. Some were excluded for misdiagnosis, and 2 each from the control and treatment group were excluded for noncompliance (the reasons were not given). Despite lack of intention-to-treat analysis, this study would have likely been statistically significant had all potential enrollees been included.

* OUTCOMES MEASURED

The number and appearance of lesions were evaluated during and after treatment. Clinical clearance was confirmed by histopathology. All adverse reactions were recorded.

* RESULTS

Twenty-one participants (84%) of the treatment group experienced complete clinical and histological clearance; 2 additional participants (8%) had partial clearance. Among the 11 control group patients, there was no reduction in the size or number of lesions.

Recurrence of actinic keratosis was observed in 2 patients (10%) 1 year after treatment. Adverse effects were seen in almost all treated patients. Severe erythema was noted in more than 80% of patients. Even after treatment at 14 weeks, about half the participants had persistent erythema.

A majority of patients also experienced moderate erosions, flaking, ulcerations, and scabbing. In the treatment group, 18 patients reduced treatment frequency to 1 or 2 times per week for varying lengths of time because of adverse effects.

J. Kendall Walker, MD, and Clint Koenig, MD, MSPH, Department of Family and Community Medicine, University of Missouri-Columbia. E-mail: WalkerJK@health.missouri.edu.

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