Original article
Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles

https://doi.org/10.1016/j.jaad.2009.07.004Get rights and content

Background

The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin.

Objective

We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp.

Methods

In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment.

Results

A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (≥75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%.

Limitations

Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients.

Conclusions

Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses.

Section snippets

Study population

Adults in general good health with 5 to 20 visible or palpable AKs, as determined by clinical assessment by the investigator, in an area greater than 25 cm2 on either the face or the balding scalp, but not both, were eligible for participation in the studies. A study patient could not have any significant condition in the treatment area that might impair evaluation, have atypical AKs (eg, AK > 1 cm2), be pregnant or lactating, have a chemical or alcohol dependency, or have an allergy to

Patient population

In the combined studies, 479 male and female patients (Fig 2) were enrolled and 453 completed the studies. The most frequent cause of discontinuation was personal reasons (10 patients), followed by AEs (6 patients). Overall, patients were predominantly male (>80%) and white (>99%), had a mean age of 64 years, and were predominantly treated on the face (>74%). The treatment groups were considered comparable with respect to demographic characteristics within and across the two studies (Table I).

Discussion

The results of these two studies indicate that imiquimod 2.5% and 3.7% creams are effective in treating AKs on the full face or scalp in a short cyclical treatment regimen. For all efficacy outcomes, both imiquimod 2.5% and 3.75% were superior to placebo. In addition, imiquimod 3.75% was superior to 2.5% with respect to partial clearance rates and percent reductions in AKs lesions. Both imiquimod creams were well tolerated, with very few patients discontinuing from the study and more than 90%

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    Funding sources: Graceway Pharmaceuticals LLC.

    Disclosure: Dr Swanson was an investigator and consultant for Graceway, and has received compensation for services. Dr Abramovits was an investigator and speaker for Graceway and has received compensation for services. Dr Berman was an advisory board member and speaker for Graceway and has received compensation for services. Mr Kulp and Dr Levy are employees of Graceway. Dr Rigel was a consultant, advisory board member, and investigator for Graceway and has received compensation for services.

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