Clinical Question: Is imiquimod (Aldara) 5 percent cream safe and effective for the treatment of actinic keratoses (AKs)?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (double-blinded)

Synopsis: As the ozone layer thins and as we live longer and have more leisure time for outdoor recreation, it is not surprising that we have more and more AKs. These traditionally have been frozen off or treated with curettage, topical fluorouracil, or even chemical peels. Imiquimod is an oddly named immune-response modifier that has anecdotally shown promise in the treatment of AKs.

In this manufacturer-sponsored study, otherwise healthy adults older than 45 years with three to 10 AKs were randomized to receive treatment with imiquimod 5 percent cream or vehicle cream. The cream was applied three times per week for eight hours at a time (left on overnight) for a total of 12 weeks. Masking of patients, physicians, and outcome assessors was appropriate, as was allocation concealment. Patients were randomized in a roughly 2:1 ratio to active treatment. Analysis, however, was on a per protocol basis rather than intention to treat, so only 36 of 52 patients were included in the final results. Six patients in the treatment group and five in the control group were excluded after randomization for misdiagnosis (they did not actually have an AK) and two in each group were excluded for noncompliance.

The results were dramatic and would have been significant even if the noncompliant patients had been included. In the imiquimod group, 84 percent of patients had complete clinical clearance of lesions at 14 weeks, compared with none in the control group. After one year, two of 25 patients in the treatment group had experienced a recurrence. The drug caused significant adverse effects in almost all patients, including severe erythema in 80 percent, severe erosions in 40 percent, and severe flaking or ulceration in 20 to 30 percent. We do not know what the long-term cosmetic results were.

Bottom Line: Imiquimod 5 percent cream is an effective treatment for AKs. However, because they are often multiple, recurrent, and develop on the face, it is important that a future trial compare cosmetic outcomes and long-term recurrence rates of cryotherapy, fluorouracil, curettage, and imiquimod. (Level of Evidence: 1b)