Low Incidence of New Actinic Keratoses After Topical 5% Imiquimod Cream Treatment: A Long-term Follow-up Study

Actinic keratoses (AKs) are epidermal lesions that occur in areas of long-term sun exposure. These AK lesions have been identified as an early clinical manifestation in the disease continuum of squamous cell carcinoma (SCC). The risk for AK lesions to develop into SCC has been reported to be as high as 6% to 10%,¹ with an even greater percentage of AKs containing cells with mutations in photooncogenes (eg, p53). Furthermore, visible AK lesions usually indicate a larger area of subclinical photodamage (ie, field of cancerization) that can manifest as clinical AK. Current therapies for AK, including cryosurgery and fluorouracil, provide varying long-term clearance rates and cosmetic outcomes.

Recently, Stockfleth et al² found imiquimod, a novel topical immune response modifier, to be safe and effective in the treatment of AK while providing favorable cosmetic results. Data suggest that imiquimod may provide long-term benefits to patients with AK by stimulating immune memory through cell-mediated antitumor pathways.^{3 - 4} The present report provides new data on the long-term follow-up of patients treated in the original study.² Patients with multiple biopsy-proven AKs participated in a randomized, double-blind, vehicle-controlled study. Patients applied topical 5% imiquimod cream or vehicle to AK lesions 3 times per week until lesions resolved or for a maximum of 12 weeks. Decreased application frequency (1 to 2 times per week) and rest periods (up to 3 weeks) were to be allowed as necessary to manage adverse events. The number, size, and appearance of AK lesions were evaluated to determine complete or partial clearance.

Thirty-six patients, 25 in the treatment group and 11 in the vehicle-control group, completed the original 12-week study.² Complete clearance of lesions at 12 weeks, verified by histologic analysis, was observed in 21 (84%) of 25 patients, and partial clearance (defined as a 50%-75% reduction in AK lesion size) occurred in 2 (8%) of 25 patients. The vehicle did not affect the number or size of AKs. The treatment with 5% imiquimod cream was well tolerated, and no treatment interruptions were needed to manage adverse events. One year after treatment with imiquimod, approximately 8% (n=2) of the patients had developed new AKs.

Twenty-five imiquimod-treated patients were observed for up to 2 years (1 patient whose lesions had completely cleared was lost to follow-up). Of these 25 patients, 16% (n=4) developed new AKs or were lost to follow-up in 18 months, whereas only 20% (n=5) developed new AKs or were lost to follow-up by 24 months after treatment. In addition, none of these patients had developed SCC in the imiquimod-treated area 2 years after treatment. Ten vehicle-treated patients were observed for 1 year. Spontaneous remission of AKs occurred in 1 patient; 9 patients developed new AKs in the vehicle-treated area; and 1 patient developed SCC in the vehicle-treated area.

Treatment with topical 5% imiquimod cream is safe and effective for AK and shows a low incidence of new AK development in the 2 years following treatment. Thus, imiquimod treatment offers an efficacious alternative to ablative therapy, providing safe and effective long-term clearance. Use of topical imiquimod also enables simultaneous treatment of clinical and subclinical AK in the field of cancerization. Furthermore, the low incidence of clinical AK in the imiquimod-treated area suggests a possible role for imiquimod-induced immune memory and antitumor response.

Correspondence: Dr Stockfleth, Campus Charité Mitte, Klinik für Dermatologie, Venerologie und Allergologie, Schumannstr 20/21, D-10117 Berlin, Germany (eggert.stockfleth@charite.de).

Financial Disclosure: None.