Literature

Clinical Pearls & Morning Reports


By Carla Rothaus

Published March 6, 2019

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Is any one of the frequently prescribed field-directed therapies for actinic keratosis more effective than the others?

Dermatologists and primary health care providers are both confronted with actinic keratosis lesions very frequently. Current guidelines provide no clear recommendations about which treatment approach is preferred. Jansen et al. conducted a randomized trial that compared treatment results with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel for patients with multiple actinic keratosis lesions in one continuous area on the head. Read the NEJM Original Article here.

Clinical Pearls

Q: Describe some of the features of actinic keratosis.

A: Actinic keratosis is the most frequent premalignant skin disease in the white population and is caused by exposure to ultraviolet radiation. With a prevalence of 37.5% among whites 50 years of age or older, actinic keratosis is one of the most frequent reasons for patients to visit a dermatologist. If left untreated, actinic keratosis may develop into squamous-cell carcinoma. The recurrence rate after treatment is high, often leading to repetitive treatments.

Q: What is the role of field-directed therapies in the management of actinic keratosis?

A: Solitary lesions can be treated with cryotherapy. However, patients with actinic keratosis often present with multiple lesions in one continuous area (so-called field change). Generally, field-directed therapies are preferred, because they not only are therapeutically effective for present actinic keratosis but also may have a prophylactic effect on the development of new lesions; in addition, they may prevent the development of squamous-cell carcinoma.

Morning Report Questions 

Q: Is any one of the frequently prescribed field-directed therapies for actinic keratosis more effective than the others?

A: The trial by Jansen et al. showed that 5% fluorouracil was significantly more effective than imiquimod, MAL-PDT, or ingenol mebutate at 12 months after the end of treatment for multiple actinic keratosis lesions in a continuous area. The cumulative probability of treatment success for fluorouracil was 74.7% (95% confidence interval [CI], 66.8 to 81.0). For imiquimod, MAL-PDT, and ingenol mebutate, these percentages were 53.9% (95% CI, 45.4 to 61.6), 37.7% (95% CI, 30.0 to 45.3), and 28.9% (95% CI, 21.8 to 36.3), respectively, according to the modified intention-to-treat analysis. Findings from the modified intention-to-treat analysis and the per-protocol analysis were similar. 

Q: What were some of the other findings of the trial by Jansen et al.?

A: The percentage of patients with 100% adherence was higher in the ingenol mebutate group (98.7%) and the MAL-PDT group (96.8%) than in the fluorouracil group (88.7%) and the imiquimod group (88.2%). Patient satisfaction with treatment and increase in health-related quality of life were highest in the fluorouracil group. Good-to-excellent cosmetic outcome was more often observed in the MAL-PDT group (96.6%) and the ingenol mebutate group (95.1%) than in the fluorouracil group (90.3%) and the imiquimod group (89.7%). There were no serious adverse events that were considered by the investigators and the medical ethics committee to be related to the trial treatment.

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