text available in print edition.)
Imiquimod cream 5% (Aldara R, 3M Pharmaceuticals) was approved by the FDA February, 1997 for the treatment of external genital and perianal warts/condyloma acuminata in adults. Anogenital warts are very common, sexually transmitted, virally induced tumors that although benign themselves, have been associated with the development of squamous cell carcinoma, particularly cervical carcinoma.1
Imiquimod is an immune response modifier. Studies have shown that it has potent immunomodulatory effects and stimulates human peripheral mononuclear cells to release interferon alpha, sub-types alpha1,alpha2, alpha5, alpha6, and alpha8. It also induces monocytes and macrophages to produce other cytokines including interleukins 1, 6, 8 and tumor necrosis factor alpha.2 The clinical relevance of these findings is not fully understood.
Previously available treatments (e.g. cryotherapy, laser vaporization, electrocautery and excision) for anogenital warts are often painful and expensive. Local therapy with podophyllin, or podophyllotoxin or trichloracetic acids, requires multiple applications, is slow acting and often causes problems associated with local inflammation.1 5-Fluorouracil, although sometimes used for external anogenital warts, is not yet approved for this indication, has neither antiviral nor immunomodulatory effects, earlier formulations were irritating and intralesional injections are painful.3,4 Unfortunately, recurrence often follows cessation of treatment following the use of these therapies.1
Recent reports suggest that multiple injections of interferon alpha produce clearance rates of 36 - 62% and are well tolerated locally; however, such treatments are time-consuming, expensive and are associated with systemic side effects.5,6
In early multicenter, double-blind, dose-ranging, vehicle controlled clinical trials, imiquimod 5% has proven effective in treating anogenital warts. In 311 patients, imiquimod 5% three times weekly completely cleared warts in 50% of patients, compared to 11% clearance in patients treated with the vehicle (p < 0.0001, intent-to-treat analysis). In a subsequent trial, daily application of the 5% cream completely cleared the warts of 52% of patients compared to 3% clearance of warts in patients using the vehicle alone (p < 0.0001, intent-to-treat analysis). In these two trials, following cessation of treatment, wart recurrence rates were 13% and 19% respectively.7
Combination treatment, using this new topical immunomodulator, imiquimod, and ablative destructive therapy, is currently under study.8 Although results are not available, it seems logical to combine imiquimod with an ablative therapy so that imiquimod could induce an immune response which has the potential to affect the virus, eliminate residual lesions, and possibly reduce recurrence rates.
The trials discussed above revealed that erythema and increased skin irritation was the
Safety During Pregnancy & Lactation
There are no adequate and well controlled studies in pregnancy and it is not known
Percutaneous absorption was minimal (less than 0.9%) following a single dose, topical application of 5 mg of imiquimod to the skin of six healthy volunteers.
Dosage and Administration of Imiquimod
Prior to retiring, a thin layer of the cream is applied to the wart area, rubbed in until cream is no longer visible, left on the skin overnight and then in the morning washed off with mild soap and water. Hands should be washed before and after being used to apply the cream. The anogenital warts should be treated three times per week. For those patients who respond, clearance of warts requires on average 8 weeks for female patients and 12 weeks for male patients.
Imiquimod has not yet been compared to any other treatment for anogenital warts. Podophyllin, the most frequently used topical treatment, is not a standardised preparation10, has an unknown shelf life10, contains potentially carcinogenic mutagens and has no known antiviral/immunomodulatory activity. Imiquimod has no mutagenic activity, is immunomodulatory/antiviral and would appear to be the drug of choice3 for multiple warts when cryotherapy is inappropriate and cost is not a problem.
This review was prepared by Rodger Hall, Vancouver.
|Return to Top|