Imiquimod — It's Not Just for Genital Warts Anymore
December 30, 2005 4 minutes read
ImiquimodIt's Not Just for Genital Warts Anymore
Abstract & Commentary
By Allan J. Wilke, MD, Residency Program Director, Associate Professor of Family Medicine, University of Alabama at Birmingham School of MedicineHuntsville Regional Medical Campus, Huntsville. Dr. Wilke reports no financial relationship to this field of study.
Synopsis: Imiquimod is safe and effective in the treatment of actinic keratoses.
Source: Korman N, et al. Dosing with 5% imiquimod cream 3 times per week for the treatment of actinic keratosis: results of two phase 3, randomized, double-blind, parallel-group, vehicle-controlled trials. Arch Dermatol. 2005;141:467-473.
This is a report of 2 Phase III, randomized, double-blind, parallel-group, vehicle-controlled trials of imiquimod 5% cream (Aldara®) in the treatment of actinic keratoses (AK). The study was conducted in 26 centers in the United States from August 2001 to August 2002. Patients had to be 18 years or older with 4 to 8 clinically diagnosed AK on the face or scalp. A total of 492 patients were enrolled, 242 receiving imiquimod and 250 receiving the vehicle cream. Patients averaged 67 years old, were predominantly male (88%), and exclusively white. The study and control groups had no statistically significant differences on entrance to the study.
Patients were treated for 16 weeks and followed for 8 weeks after treatment. Partial clearance (the proportion of patients at the 8-week post-treatment visit with ≥ 75% reduction in the number of baseline AK) occurred in 155 (64.0%) of the imiquimod patients and 34 (13.6%) of the control patients (number-needed-to-treat [NNT], 2.0). Complete clearance occurred in 117 (48.3%) imiquimod patients and 18 (7.2%) control patients (NNT 2.4). (These patients were included in the partial clearance numbers.) There was an 86.6% reduction in the number of baseline AK in 50% of the imiquimod patients, but only 14.3% of controls. The investigators monitored for adverse events. There were 176 (72.7%) in the imiquimod group and 149 (59.6%) in the control group. They noted that for patients in the imiquimod group, there was a direct relationship between the intensity of erythema and the clearance rate. Other significant adverse events (and their rates in the study group vs the control group) were: itching at the target site (29% vs 4%), burning at the target site (7% vs 1%), itching at a remote site (7% vs 1%), and pain at the target site (4% vs 0%).
Commentary
AK occur mainly on sun-exposed skin, scalp, face, arms, and hands. Classically, they are described as being rough-textured and pink with irregular borders. They are precursor lesions for squamous cell carcinomas (SCC). As many as 20% of people with AK will go one to develop SCC. Therefore, treatment of AK can prevent skin cancer. The methods of treatment include mechanical (cryosurgery with liquid nitrogen, excision, electrodessication with curettage, chemical peels, laser resurfacing) and medical (topical fluorouracil [5-FU], diclofenac gel, topical aminolevulinic acid plus blue light). The authors speculate that imiquimod is effective because it stimulates the production of interferon a, tumor necrosis factor α, and interleukin 12, which causes a cytokine cascade and a T-lymphocyte immune response.
The FDA approved imiquimod for AK in March 2004 and for superficial basal cell carcinoma (BCC) in July 2004. The estimated AK treatment cost of imiquimod twice weekly for 16 weeks is more than $500, compared to $75 for a twice daily, 4-week course of generic 5-FU.1 There is some anecdotal evidence that use of imiquimod is associated with systemic side effects, specifically, fatigue and an influenza-like illness.2 Angioedema has been reported, too.3 Since imiquimod is detectable in only nanogram amounts in human serum, it is possible that the systemic adverse effects may be caused by the release to the cytokines. There are no head-to-head studies that compare imiquimod and 5-FU.
In a second article in this issue of Archives of Dermatology, Venna and colleagues report a small study of the ability of dermatologists to clinically identify AK.4 They chose a high-risk group of people, those with a history of skin cancer who were presenting for definitive surgical treatment of their cancers. They defined AK as "an erythematosus papule 2 to 5 mm in diameter, with an adherent scale and a palpable rough surface." All 3 physicians had to agree on the clinical diagnosis of AK. Two dermatologists and a second-year dermatology resident examined the first 18 patients who met their inclusion and exclusion criteria. A total of 23 lesions were identified as AK. All patients had their lesions biopsied; histologically, 17 were AK, 1 was a combination of AK and an irritated seborrheic keratosis, 3 were SCC, 1 was a BCC, and 1 was a lentigo maligna. This is an unimpressive showing and suggests to me that we need to biopsy more suspicious lesions than what we might think. It also makes me wonder how many people in the Korman study were treating their SCC with imiquimod.
Note: Korman et al received financial support from 3M Pharmaceuticals, the manufacturer of Aldara®.
References
1. Imiquimod (Aldara) for actinic keratoses. Med Lett Drugs Ther. 2004;46:42-43.
2. Systemic reactions to imiquimod (Aldara). Med Lett Drugs Ther. 2004;46:92.
3. Barton JC. Angioedema associated with imiquimod. J Am Acad Dermatol. 2004;51:477-478.
4. Venna SS, et al. Clinical recognition of actinic keratoses in a high-risk population: how good are we? Arch Dermatol. 2005;141:507-509.
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