Systematic Literature Review and Network Meta-analysis of the Efficacy and Acceptability of Interventions in Actinic Keratoses

Acta Derm Venereol. 2021 Jan 4;101(1):adv00358. doi: 10.2340/00015555-3690.


A systematic literature review was conducted to identify and qualitatively assess randomized controlled trials in immunocompetent patients ≥ 18 years with head- region lesions of actinic keratoses who were treated with field-directed, lesion-directed and other therapies. Network meta-analysis was used to quantitatively evaluate field-directed therapies (5-fluorouracil formulations, diclofenac sodium, imiquimod, ingenol mebutate, 5-aminolevulinic acid or methyl aminolevulinate plus photodynamic therapy) using complete clearance or partial clearance of actinic keratoses lesions, and adverse event-related withdrawals as a proxy of acceptability. Of 2,863 references identified, 75 trials reported in 151 publications were included. In summary, comparative network meta-analysis evaluation showed that 5-fluorouracil formulations were the most efficacious interventions examined. 5-fluorouracil 4%, which was recently approved, showed a comparable efficacy profile to 5-fluorouracil 5%, and had satisfactory acceptability outcomes.

Keywords: field-directed intervention; network meta-analysis; systematic literature review; actinic keratosis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diterpenes* / therapeutic use
  • Humans
  • Imiquimod / adverse effects
  • Keratosis, Actinic* / diagnosis
  • Keratosis, Actinic* / drug therapy
  • Network Meta-Analysis
  • Photochemotherapy*
  • Treatment Outcome


  • Diterpenes
  • Imiquimod