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Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehicle-controlled trials

https://doi.org/10.1016/j.jaad.2003.12.010Get rights and content

Abstract

Background

The immune system plays a critical role in the development and pathogenesis of actinic keratosis (AK). Imiquimod has been shown to stimulate the cutaneous immune response and be effective for the treatment of nonmelanoma skin cancers.

Objective

Two phase III, randomized, double-blind, vehicle-controlled studies evaluated the efficacy of imiquimod 5% cream compared with vehicle in the treatment of AK lesions on the face and balding scalp.

Methods

A total of 436 participants at 24 centers in the United States and Canada were randomized to either imiquimod 5% or vehicle cream. Study cream was applied one time per day, 2 days per week for 16 weeks. Clearance of AK lesions was clinically assessed at an 8-week posttreatment visit.

Results

The complete clearance rate was 45.1% for the imiquimod group and 3.2% for the vehicle group. The difference in complete clearance rates (imiquimod minus vehicle) was 41.9% with a 95% confidence interval of 34.9% to 49%. The partial (≥75%) clearance rate was 59.1% for the imiquimod group and 11.8% for the vehicle group. The difference in partial clearance rates (imiquimod minus vehicle) was 47.3% with a 95% confidence interval of 39.5% to 55.1%. The median percent reduction in AK lesions was 83.3% for the imiquimod group and 0% for the vehicle group. Local skin reactions were common. Severe erythema was reported by 17.7% of participants who received imiquimod and 2.3% of participants who received vehicle. Overall, imiquimod was very well tolerated.

Conclusion

Imiquimod 5% cream used 2 times per week for 16 weeks is an effective and well-tolerated treatment for AK.

Section snippets

Study population

Eligible participants were otherwise healthy men and women at least 18 years of age with 4 to 8 clinically diagnosed AK lesions located within a contiguous 25-cm2 treatment area on the face or balding scalp, but not both. Participants were to be excluded from the study if they had any condition in the treatment area that could be exacerbated by treatment with imiquimod 5% cream or that would impair the examination of the treatment area. If a participant had previously received treatment with

Study population

Between the two studies, a total of 623 people were screened and 436 (217 in one study and 219 in the other) were enrolled. Violations of inclusion or exclusion criteria were the most common reasons for study ineligibility. Overall, 215 participants were randomized to treatment with imiquimod 5% cream, and 221 were randomized to treatment with vehicle cream. Participant accountability is shown in Fig 1. There were no significant differences between treatment groups for age, sex, race, or

Discussion

Imiquimod 5% cream is an effective and well-tolerated treatment option for AK lesions on the face and scalp. The results confirm earlier study results and published anecdotes that showed imiquimod 5% cream was an effective treatment for AK. The benefits of treatment with topical imiquimod 5% cream include complete clearance of AK lesions for 45.1% of participants and partial clearance (≥75% reduction in the number of baseline lesions) for 59.1% of participants.

According to this protocol,

Acknowledgements

We thank Nanda Gosala, MD, for medical monitoring; Mary Owens, MD, for editorial contributions; Scott McKane for statistical analyses support; and Áine Skow for manuscript preparation.

The following are principal investigators who participated in the study: Scott Dinehart, MD (coordinating investigator); Mark Lebwohl, MD (coordinating investigator); Donald Belsito, MD; Robert Brown, MD; Charles Dugan, MD; Richard Fitzpatrick, MD; Scott Fosko, MD; Glenn Goldman, MD; William Harwell, MD; Joseph

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Supported by 3M Pharmaceuticals, St Paul, Minnesota.

Disclosure: Drs Lebwohl, Dinehart, Whiting, P. Lee, Tawfik, and Jorizzo have received support from 3M Pharmaceuticals for performing clinical trials. Drs Jorizzo and P. Lee have served as consultants for 3M Pharmaceuticals. Drs Lebwohl and Tawfik have received speaking honoraria. Dr J. Lee and Mr Fox are employees of 3M Pharmaceuticals.

Portions of this information have been presented at the 62nd Annual Meeting of the American Academy of Dermatology, Washington, DC, February 6-11, 2004 and at ACADEMY 2003, Chicago, Ill, July 25-29, 2003.

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