Community-Based Practice Variations in Topical Treatment of Actinic Keratoses

Actinic keratoses (AKs) are precancerous skin lesions afflicting nearly 58 million people in the United States per year and costing over a billion dollars annually to treat.^1,2 Two of the most widely used topical field-based treatments for AKs are fluorouracil and imiquimod.³ Although variations exist in how these topical medications are prescribed in terms of frequency, duration, and strength for AK treatment,⁴ no studies have systematically examined how patient and health care provider factors impact prescribed regimens. Using data from a large community-based population, we examined how variations in fluorouracil and imiquimod prescription patterns for AKs treatment was influenced by patient age, sex, AK anatomic site, and prescriber type.

Kaiser Permanente Northern California (KPNC) is a large, integrated health care delivery system that provides comprehensive health care to a community-based population of over 3.4 million members. We identified KPNC members 18 years or older diagnosed with an AK (International Statistical Classification of Diseases and Related Health Problems, Ninth Revision code 702.0) in 2007 who were prescribed either fluorouracil (n = 5062) or imiquimod (n = 638) for AK treatment. The association between age, sex, anatomic AK location, and health care provider type and each of the 3 outcomes (frequency, duration, and strength) was evaluated using linear regression. Strength was defined as “low” (less than 5%) or “high” (5% or greater). Duration ranged from 1 week to greater than 6 weeks. Frequency ranged from once weekly to more than twice daily. This study was approved by the Kaiser Foundation Research Institute institutional review board. The Declaration of Helsinki protocols were followed, and a waiver of informed consent was obtained.

Characteristics of the study cohort are summarized in the Table. Mean (SD) age was 66.4 (11.6) years; 3383 patients (59.3%) were men; the most common AK site was the head and neck (n = 2355  [41.3%]); and the majority of prescribers were dermatologists (n = 5386 [94.5%]). Older patients were prescribed less frequent regimens. With respect to sex, male patients were more frequently prescribed fluorouracil than imiquimod, and were prescribed higher strength fluorouracil than female patients. Actinic keratoses arising on the head and neck were treated with lower strength agents than other anatomic locations. Dermatologists were more likely to prescribe imiquimod, to prescribe higher frequency of application regimens, and treat for a shorter duration as compared with nondermatologists. These treatment variations are illustrated in the Figure.

We systematically show that patient characteristics including age, sex, and AK anatomic site are associated with variation in topical AK treatment regimens. The difference in prescribing patterns by age and sex of the patient may be influenced by physician perception and patient expectations of tolerability. The variations in prescribing patterns between dermatologists and nondermatologists may be explained by higher AK burden among patients seeking specialty care and greater comfort in varying the regimen to achieve the desired clinical outcome by specialty health care providers.⁴

Strengths of this study include the use of an electronic pharmacy database for exposure measurement, allowing for accurate capture of dispensed medication, as well as the ability to comprehensively capture information on patient and provider factors. Limitations include that we may have underpowered to detect associations with imiquimod, because our study period focused on a time when imiquimod was first being introduced to clinical practice, and the fact that some of the absolute differences within outcome categories are small and need to be interpreted in an appropriate clinical context.

We report significant differences in prescribing patterns for fluorouracil and imiquimod for AK treatment, which are associated with patient and prescriber factors. Our findings have implications for future real-world comparative effectiveness studies that examine AK treatments and associated clinical outcomes.

Corresponding Author: Maryam M. Asgari, MD, MPH, Department of Dermatology, Massachusetts General Hospital, 50 Staniford St, Ste 230A, Boston, Massachusetts 02114 (harvardskinstudies@partners.org).

Published Online: April 5, 2017. doi:10.1001/jamadermatol.2016.6251

Author Contributions: Drs Asgari had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Asgari.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Storer, Zhu, Ford, Neugebauer, Asgari.

Critical revision of the manuscript for important intellectual content: Storer, Sokil, Neugebauer, Asgari.

Statistical analysis: Zhu, Neugebauer.

Obtained funding: Neugebauer, Asgari.

Administrative, technical, or material support: Sokil, Neugebauer.

Supervision: Neugebauer, Asgari.

Conflict of Interests Disclosure: Dr Asgari receives grant funding from Pfizer Inc and Valeant Pharmaceuticals.

Funding/Support: This work was supported by the National Institute of Arthritis Musculoskeletal and Skin Diseases (grant No. R03AR064014 to M.A.).

Role of the Funder/Sponsor: The funder/sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.