Although the use of 5-fluorouracil (5-FU) has been shown to reduce the overall risk for keratinocyte carcinoma (KC) compared with imiquimod therapy, in a real-life practice setting of patients with actinic keratosis (AK), no significant differences in the short- or long-term risk for site-specific KCs have been observed with 5-FU compared with imiquimod treatment.

A retrospective, longitudinal cohort study was conducted among all Kaiser Permanente Northern California health plan members aged 18 years or older who had been diagnosed with an AK in 2007 and had filled a prescription for 5-FU or imiquimod. Cohort members were followed for the development of any subsequent KC (ie, any KC, any basal cell carcinoma, or any squamous cell carcinoma). Results of the study were published in the Journal of the American Academy of Dermatology.

The investigators sought to compare the effectiveness of 5-FU vs imiquimod for the prevention of KCs. A total of 5700 patients participated in the study; 5062 of patients had filled a prescription for 5-FU and 638 had filled a prescription for imiquimod. They used an intention-to-treat analysis that controlled for potential confounding variables to calculate 2- and 5-year risk differences for the development of KCs overall and in field-treated areas.

The use of 5-FU was associated with a statistically significantly decreased risk for the development of any KC compared with the use of imiquimod (adjusted hazard ratio [aHR] 0.86; 95% CI, 0.76-0.97). In contrast, no significant differences in risk were reported according to tumor subtype: (1) squamous cell carcinoma: aHR 0.89; 95% CI, 0.74-1.07; (2) basal cell carcinoma: aHR 0.87; 95% CI, 0.74-1.03; or (3) site-specific KC: aHR 0.96; 95% CI, 0.81-1.14. Moreover, no significant differences in 2- or 5-year cumulative risk for KC was reported among participants treated with 5-FU compared with those treated with imiquimod.

A major limitation of the study is that generalizability of the findings to other practice settings may be limited. A major strength of the analysis is the use of Kaiser Permanente Northern California’s closed, prepaid, integrated healthcare system, which allowed for a real-world comparison of the efficacy of 5-FU and imiquimod within a well-characterized, stable population.

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The investigators concluded that, in view of the burden that AKs pose to the healthcare system, including their high prevalence, significant cost, and potential for malignant progression, dermatologists should be aware of how available treatment options compare with respect to their effectiveness in the prevention of KCs.

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Reference

Neugebauer R, Su KA, Zhu Z, et al. Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: a cohort study [published online November 17, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.024