Imiquimod is an immunomodulator. Application of the drug results in increased levels of interferons α, β, and γ and tumor necrosis factor α in lesional tissues. Further, keratinocytes exposed to imiquimod release increased levels of IFN-α, IL-6, and IL-8. These and other cytokines activate and sensitize the local cellular immune system, including, but not limited to, natural killer and cytotoxic T cells. The cascade results in a localized immune response against the abnormal cells in the application area.23-26
Salasche et al28 conducted a 25-patient, open-label trial using 5% imiquimod 3 times a week. The therapeutic regimen consisted of 4 weeks of treatment, followed by a 1-month resting period. No more than an additional 2 cycles of treatment were given if total clearance did not occur by the end of the first rest period. At the end of the first cycle, 15 of the 33 study areas were devoid of any lesions. After the second cycle, an additional 12 sites were cleared. Only one patient underwent a third cycle of treatment, resulting in a 75% clearance in the study area. Overall, 82% of the treated sites were cleared using this therapy. Some patients experienced a mild to moderate local irritation, which was well tolerated without complication. However, 5 patients reported severe medication reactions, all of which occurred during the first cycle. These reactions followed an intense and early response to therapy.28
Persaud et al29 conducted a 22-patient study applying 5% imiquimod cream to half of each patient’s body 3 times a week for a maximum of 8 weeks. The treatment period was followed by an 8-week monitoring period. The 17 patients who completed the study had mean AK reduction of 3.9 on the imiquimod side per patient compared with a 0.5 lesion reduction on the vehicle side (P<.005). As a result of treatment, 14 of the 17 patients experienced mild to moderate erythema, pruritus, and/or scabbing. Further, to complete the study, 12 patients required 1 or 2 rest periods, followed by a reduction in application frequency.29
Stockfleth et al30 conducted a 6-patient study examining the efficacy of 5% imiquimod applied 2 to 3 times a week for 6 to 8 weeks. On completion of the treatment, all patients were clinically and histologically cleared of all AKs in their test areas. Patients were followed for a maximum of 12 months and had no recurrence of disease in their treated areas. All patients decreased their dosage from 3 times a week to 2 times a week for more than half of individual treatment periods. The treatment was well tolerated, with only mild to moderate pruritus and erythema reported.30
In another study, Stockfleth et al31 treated 36 patients with 5% imiquimod 3 times a week for a maximum of 12 weeks. By the 14th week of the study, 21 of the 25 patients treated with imiquimod experienced complete clinical and histologic clearance in their study areas. Further, the 15 patients who maintained a 3-times-per-week application protocol all experienced total clearance in their study areas. These results were significant in comparison with the clearance rate in the control group (P<.001). During the treatment period, every patient using imiquimod experienced some type of mild to severe adverse reactions. The 5 most common occurrences were erythema, scabbing, erosions, flaking, and ulcerations.31 Recently, a phase 3 trial evaluating imiquimod for the treatment of AKs was completed.