What is the best treatment for actinic keratosis?

Bottom Line

This network meta-analysis found that 5-fluorouracil (5-FU) is the most effective treatment for actinic keratosis, based on the outcome of participant complete clearance. The authors caution that the final choice of therapy should take into account other factors, such as tolerability (which might favor imiquimod) or cost (which would favor cryotherapy). (LOE = 1a-)


Gupta AK, Paquet M. Network meta-analysis of the outcome ‘participant complete clearance’ in nonimmunosuppressed participants of eight interventions for actinic keratosis: a follow-up on a Cochrane review. Br J Dermatol 2013;169(2):250-259.

Study Design: Meta-analysis (randomized controlled trials)

Funding: Unknown/not stated

Setting: Various (meta-analysis)

Allocation: Unknown


A network meta-analysis is a relatively new approach to synthesizing the medical literature. A traditional meta-analysis combines results from similar trials (for example, 5-FU versus placebo for the treatment of actinic keratosis); a network meta-analysis instead allows us to compare interventions indirectly. For example, if both 5-FU and imiquimod were compared with placebo in several studies, we can determine the relative efficacy of the 2 drugs compared with each other. The authors built on a recent Cochrane review, and identified a total of 32 studies comparing treatments to each other and/or to placebo. The outcome used was “participant complete clearance,” which is a good patient-oriented outcome (although the exact definition varied somewhat between studies). The authors concluded that 5-FU 5% is the best treatment, followed by imiquimod, 5-aminolaevulinic acid-photodynamic therapy, ingenol mebutate, and methyl aminolaevulinate-photodynamic therapy, which were all similarly effective. Cryotherapy was less effective than all of these, diclofenac/hyaluronic acid was even less effective, and placebo was least effective of all (not surprisingly). All studies had a follow-up of one year or less, a limitation.

Mark H. Ebell, MD, MS
Associate Professor
University of Georgia
Athens, GA


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