Original article
A real-world, community-based cohort study comparing the effectiveness of topical fluorouracil versus topical imiquimod for the treatment of actinic keratosis

https://doi.org/10.1016/j.jaad.2017.12.042Get rights and content

Background

The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting.

Objective

We compared the effectiveness of 5-fluorouracil and imiquimod in reducing risk for subsequent AKs in a large, integrated health care delivery system in northern California.

Methods

In this cohort study, we identified adult health plan members who had an AK diagnosed in 2007 and who subsequently filled a prescription for 5-fluorouracil or imiquimod (N = 5700). We followed subjects for subsequent AKs identified by the International Classification of Diseases codes and estimated the 2-year (short-term) and 5-year (long-term) differences in cumulative risk while controlling for potential confounding by pretreatment variables.

Results

5-Fluorouracil reduced the short-term incidence of subsequent AKs (cumulative risk difference -4.54% [95% confidence interval, -7.91% to -1.17%]), but there was no statistically significant evidence of a long-term decreased risk (cumulative risk difference -1.43% [95% confidence interval, -3.43% to 0.05%]) compared with that with imiquimod.

Limitations

This is a retrospective study with limited ascertainment of all relevant potential confounding variables.

Conclusion

We found that 5-fluorouracil appeared to be significantly more effective than imiquimod in the short-term, but not long-term, prevention of subsequent AKs.

Section snippets

Materials and methods

We performed a retrospective longitudinal cohort study of all Kaiser Permanente Northern California (KPNC) members with a diagnosed AK who filled prescriptions for 5-FU (n = 5062) or Imq (n = 638) in 2007. Cohort members were followed for subsequent AK diagnosis.

Results

Of the 5700 patients in the cohort, 5062 were exposed to 5-FU and 638 were exposed to Imq. In the majority (n = 4946), a subsequent AK was diagnosed during follow-up. Of the 754 patients with no subsequent AK diagnosis, 289 were censored due to a membership gap of greater than 3 month, 100 were censored due to death, and 365 were followed through to the end of the study period. In total, 281 patients had no subsequent AK diagnosis before 2 years, and 441 had no subsequent AK diagnosis before

Discussion

In this large cohort study based in a real-world HMO setting with comprehensive integrated health care delivery, we have shown that 5-FU may be more effective than Imq in preventing subsequent AKs in the short term, but we did not find statistically significant evidence of a difference in the long term.

To our knowledge, this is the first study to compare the effectiveness of 5-FU and Imq in preventing subsequent AKs in a real-world setting. Only 2 small randomized trials have directly compared

References (20)

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  • Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: A cohort study

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    KPNC maintains a computerized record system with detailed information on members’ demographic characteristics; clinical visits; pharmacy dispensed medications; laboratory, pathology, and radiology results; and other medical services. The study cohort has been described previously13 and consists of adult KPNC members in whom AK was diagnosed (ICD-9 code 702.0) between January 1, 2007, and December 31, 2007, and who received subsequent topical AK field treatment with 5-FU or imiquimod (N = 8556) (Fig 1). The year 2007 was selected because imiquimod was not available before 2007 and doing so allowed for electronic review of all outpatient ambulatory notes, which facilitated abstraction of information on treatment indication, anatomic site of application, and site of subsequent KC.

  • Poor Adherence to Self-Applied Topical Drug Treatment Is a Common Source of Low Lesion Clearance in Patients with Actinic Keratosis—A Cross-Sectional Study

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Funding sources: Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grants R03AR064014 and K24AR069760 to MA).

Disclosure: Dr Asgari has research contracts with Pfizer and Valeant Pharmaceuticals that are not relevant to the contents of this manuscript. Dr Neugebauer, Ms Levandoski, Ms Zhu, Ms Sokil, Dr Chren, and Dr Friedman have no conflicts of interest to disclosed.

Reprints not available from the authors.

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© 2017 by the American Academy of Dermatology, Inc.