Treatment of genital warts with an immune-response modifier (imiquimod)

Background: Genital warts are a common sexually transmitted disease caused by human papillomavirus. Imiquimod is a novel immune-response modifier capable of inducing a variety of cytokines, including interferon alfa, tumor necrosis factor-alpha, as well as interleukins 1, 6, and 8. In animal models imiquimod has demonstrated antiviral, antitumor, and adjuvant activity. In vitro, imiquimod has no antiviral or antitumor activity. Objective: Our purpose was to determine the safety and efficacy of topical imiquimod for the treatment of external genital warts. Methods: This prospective double-blind, placebo-controlled, parallel design clinical trial was performed in three outpatient centers, a public health clinic, a university-based clinic, and a private practice. One hundred eight patients with external genital wafts (predominantly white men) were entered into the trial. Fifty-one patients were randomly selected to receive 5% imiquimod cream; 57 patients were randomly chosen to receive placebo cream. Study medication was applied three times weekly for up to 8 weeks. Patients whose warts cleared completely were observed for up to 10 weeks to determine recurrence rates. Results: In the intent-to-treat analysis, the warts of 37% (19 of 51) of the imiquimod-treated patients and 0% (0 of 57) of the placebo group cleared completely (p < 0.001). In addition, many patients experienced a partial response. A reduction in baseline wart area of 80% or more was observed in 62% of imiquimod-treated patients (28 of 45) and 4% of the placebo group (2 of 50) (p < 0.001); a 50% reduction or more in wart area was noted in 76% of imiquimod-treated patients (34 of 45) and 8% of placebo recipients (4 of 50) (p < 0.001). Of imiquimod-treated patients whose warts cleared completely and who finished the 10-week follow-up period. 19% (3 of 16) experienced recurrences of warts. Imiquimod-treated patients experienced a significantly greater number of local inflammatory reactions than the placebo group. Symptoms and signs associated with the local inflammatory reactions included itching (54.2%), erythema (33.3%), burning (31.3%), irritation (16.7%), tenderness (12.5%), ulceration (10.4%), erosion (10.4%), and pain (8.3%). There were no differences in systemic reactions or laboratory abnormalities between treatment groups. Conclusion: Topical 5% imiquimod cream appears to have a significant therapeutic effect in the treatment of external genital warts.