• João Costa Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa; Unidade de Farmacologia Clínica. Instituto de Medicina Molecular. Faculdade de Medicina. Universidade de Lisboa
  • Rita Sousa Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa
  • Joana Alarcão Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa
  • António Vaz-Carneiro Centro de Estudos de Medicina Baseada na Evidência. Faculdade de Medicina. Universidade de Lisboa
  • Paulo Filipe Serviço de Dermatologia do Centro Hospitalar Lisboa Norte e Unidade de Investigação em Dermatologia. Instituto de Medicina Molecular. Faculdade de Medicina. Universidade de Lisboa. Lisboa, Portugal
Keywords: Diterpenes, Keratosis, actinic, Meta-analysis, Randomized controlled trials


Introduction: Actinic keratosis is the most common premalignant lesion. The therapeutic approach to patients with multiple lesions involves field-directed treatment.

Objective: To evaluate the efficacy and safety of ingenol mebutato, a new drug treatment for topical field-directed treatment of actinic keratosis.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs) trials.

Data sources: Medline and Cochrane Library (June 2014).

Study selection: Two reviewers independently searched for studies and retrieved their characteristics and data estimates.

Data synthesis: Random-effects meta-analysis. Heterogeneity was assessed with the I2 test.

Results: Six trials (n = 1,492) versus placebo were included. The odds of a patient experiencing complete removal of the lesions was 17 (95%CI: 9 to 31, I2 = 0%) and 8.5 (95% CI: 5 to 15, I2 = 0%) times higher, compared to placebo, in the face/scalp and trunk/extremities, respectively. The incidence of adverse events related to treatment was higher in the group of mebutato ingenol (+23%, 95%CI: 11 to 35%), with no differences between groups in the discontinuation rate due to adverse events.

Conclusions: Mebutato of ingenol is efficacious in the treatment of actinic keratosis. Compared to other field-directed treatments available in Portugal, its therapeutic value comes from the favourable safety profile and tolerability, simplicity and short duration of the treatment regimen and the possibility of different treatment to injuries according to anatomical location (individualization of therapy). Future studies should directly compare the different therapeutic options and evaluate the effectiveness of the same in the real world.


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How to Cite
Costa, J., Sousa, R., Alarcão, J., Vaz-Carneiro, A., & Filipe, P. (1). EFFICACY AND SAFETY OF INGENOL MEBUTATE IN THE TREATMENT OF ACTINIC KERATOSIS − A SYSTEMATIC REVIEW AND META-ANALYSIS. Journal of the Portuguese Society of Dermatology and Venereology, 72(4), 481-492. https://doi.org/10.29021/spdv.72.4.317
Original Articles