Recent Therapeutic Advances in Dermatology
Authors: G M Lipper, K A Arndt, J S Dover
Journal: JAMA (2000)

Imiquimod: Warts and Beyond Imiquimod (Aldara, 3M Pharmaceuticals, St Paul, Minn), a novel immunomodulatory imidazoquinolin heterocyclic amine, has shown potent antiviral and antitumor action both experimentally and in recent clinical trials. In clinical practice, the drug was approved by the Food and Drug Administration for topical application as a treatment of anogenital condylomata acuminata, and can be easily applied to affected areas by the patient at home, with 5% imiquimod cream left on overnight (6-10 hours) and then washed off, used 3 days a week for 16 weeks or until all visible warts have disappeared. Imiquimod shows no intrinsic antiviral or antineoplastic effect, but it is thought to owe its activity to in vivo induction of interferon alfa (IFN-a) subtypes 1, 2, 5, 6, and 8, and tumor necrosis factora(TNF-a).Multiplecell types including human peripheral blood mononuclearcellsandneonatal foreskin keratinocytes have been shown to produce these cytokines in the presence of imiquimod. In a recent clinical trial, 50%ofpatients applying5%imiquimod cream(n = 109;3times/wkfor16weeks) compared with 21% of patients applying 1% imiquimod cream (n = 102) and 11% of patients in a placebo vehicle group (n = 100) achieved eradication of all treated baseline warts. These results, which were obtained in a randomized, double-blinded,placebo-controlledfashion,compare favorablywithmore laborintensive and potentially painful standard rapid therapies such as excision, cryosurgery,electrosurgicalablation,and laser vaporization. In the above study, application of 5% imiquimod cream was not associated with systemic adverse symptoms, but did cause local inflammatory reactions including erythema (67%) that was characterized as severe at some point in 6 patients (5.7%). Recurrence in areas treated with 5% imiquimod cream occurred in 6 (13%) of 45 patients compared with no recurrences (0/ 18) in patients using 1% cream and a 10% recurrence rate in the placebo group (1/10). These rates compare favorably with alternative therapies such as cryotherapy, laser vaporization, and podophyllin, although comparison trials would be useful. This is especially true for podophyllin, a commonly used topical wart therapy that is less expensive than imiquimod and can be similarly applied at home by the patient. A randomized controlled trial comparing respective clearance rates, recurrence rates, and adverse effect profiles for these 2 competing topical therapies would be clinically useful. Evidence suggests that imiquimod may work by inducing a cell-mediated immune response to clear wart-inducing human papillomavirus with reduction in human papillomavirus viral load during treatment correlating with increased local production of IFN-a, IFN-b, and IFN-g and TNF-a. Similar clearance results have been obtained with intralesional injection of IFN-a, which cannot be topically absorbed, is costly ($350/10-million U vial of IFN-a 2b), and requires multiple visits for painful injections, with the added risk of systemic adverse effects. Topically applied imiquimod cream also effectively treated the poxvirusinducedmolluscumcontagiosuminarecent,prospective,controlledclinicaltrial, and thus is a reasonable topical therapy alternative for refractory and extensive molluscumlesionsnotresponsivetocryotherapy or tape-stripping (a mechanical techniqueforsheeringoffsolitarylesions). Otherclinicalapplicationsforimiquimod may be around the corner. For instance, oral imiquimodhasshownantitumoreffects on several murine tumor cell lines, withantitumoreffectssignificantlydiminishedbyconcurrentadministrationofantiserumtomurineIFN-a.Thesedatamay yield future clinical applications, with clinical trials currently under way to evaluate the effect of topical imiquimod oncutaneousmalignancies suchasbasal cell carcinoma, squamous cell carcinoma,andhumanpapillomavirus–induced dysplastic lesions.