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Tirbanibulin for actinic keratosis


Actinic keratosis is a common dermatological disorder which can develop into squamous cell carcinoma. If there are a number of confluent lesions (actinic field change), the current treatment usually consists of fluorouracil cream, the drug of first choice. In July 2021, an ointment containing tirbanibulin (Klisyri®) was authorised for the treatment of actinic keratosis. Tirbanibulin is the first tyrosine kinase inhibitor intended for cutaneous application. An indirect comparison by means of a network meta-analysis found no significant differences in efficacy between tirbanibulin ointment, fluorouracil cream and imiquimod cream. 

  • When patients with an actinic field change are treated with tirbanibulin ointment, the lesions disappear completely in a significantly higher percentage of patients than when they are treated with placebo (49% vs. 9%).
  • In 71% of the treated patients, the lesions return or new lesions arise at the treated site. This is comparable to existing therapies.
  • An indirect comparison by means of a network meta-analysis found no difference in efficacy between tirbanibulin ointment and fluorouracil cream or imiquimod cream.
  • Since there have been no direct comparative studies, no indication of the position of tirbanibulin relative to existing treatments can be given. 
  • Advantages of treatment with tirbanibulin ointment are the short duration (5 days) and the possibly mild adverse effects, while disadvantages include the lack of experience with this drug and its higher price. 
  • Based on the above, the Ge-Bu drug rating for tirbanibulin ointment is +/-

  1. Nederlandse Vereniging voor Dermatologie en Venereologie. Richtlijn NVDV Actinische keratose 2021. Available from: https://richtlijnendatabase.nl/richtlijn/actinische_keratose/startpagina_-_actinische_keratose_ak.html. Accessed 20-02-2022.
  2. Blauvelt A, Kempers S, Lain E, Schlesinger T, Tyring S, Forman S, et al. Phase 3 Tirbanibulin for Actinic Keratosis Group. Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis. N Engl J Med. 2021 Feb 11;384(6):512-520. doi: 10.1056/NEJMoa2024040. 
  3. Heppt MV, Dykukha I, Graziadio S, Salido-Vallejo R, Chapman-Rounds M, Edwards M. Comparative Efficacy and Safety of Tirbanibulin for Actinic Keratosis of the Face and Scalp in Europe: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. J Clin Med. 2022 Mar 16;11(6):1654. doi: 10.3390/jcm11061654.
  4. Nederlands Huisartsen Genootschap. NHG-Standaard Verdachte huidafwijkingen. 2017. laatste aanpassing maart 2017. Available from: https://richtlijnen.nhg.org/standaarden/verdachte-huidafwijkingen.
  5. Kerst AJ, Janssens HJ. Behandeling actinische keratose met 5-FU-crème. Gebu. 2019;53(9):81-85.
  6. Steeb T, Wessely A, Petzold A, Brinker TJ, Schmitz L, Leiter U, et al. Evaluation of Long-term Clearance Rates of Interventions for Actinic Keratosis: A Systematic Review and Network Meta-analysis. JAMA Dermatol. 2021 Sep 1;157(9):1066-1077. doi: 10.1001/jamadermatol.2021.2779. 
  7. EMA. Productinformatie Klisyri®. Available from: https://www.ema.europa.eu/en/documents/product-information/klisyri-epar-product-information_nl.pdf. Accessed 20-02-2022.
  8. Zorginstituut Nederland. Medicijnkosten.nl. Kosten Klisyri zalf 10mg/g in sachet. Available from: https://www.medicijnkosten.nl/medicijn?artikel=KLISYRI+ZALF+10MG%2FG+IN+SACHET&id=457a55dfeab82fa93105b2a91df67733. Accessed 16-04-2022.
  9. G-Standaard april 2021. Avaialble from: KNMP Kennisbank. Accessed 16-04-2022.
  10. Informatorium Medicamentorum. Den Haag: KNMP, 2022. Available from : https://kennisbank.knmp.nl/login?destination=.
  11. Gilchrest BA. Tirbanibulin: A New Topical Therapy for Actinic Keratoses With a Novel Mechanism of Action and Improved Ease of Use. Clin Pharmacol Drug Dev. 2021 Oct;10(10):1126-1129. doi: 10.1002/cpdd.1024. 
  12. Cramer P, Stockfleth E. Actinic keratosis: where do we stand and where is the future going to take us? Expert Opin Emerg Drugs. 2020 Mar;25(1):49-58. doi: 10.1080/14728214.2020.1730810. 
  13. Willenbrink TJ, Ruiz ES, Cornejo CM, Schmults CD, Arron ST, Jambusaria-Pahlajani A. Field cancerization: Definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol. 2020 Sep;83(3):709-717. doi: 10.1016/j.jaad.2020.03.126. 
  14. Bakshi A, Shafi R, Nelson J, Cantrell WC, Subhadarshani S, Andea A, et al. The clinical course of actinic keratosis correlates with underlying molecular mechanisms. Br J Dermatol. 2020 Apr;182(4):995-1002. doi: 10.1111/bjd.18338
  15. Werner RN, Sammain A, Erdmann R, Hartmann V, Stockfleth E, Nast A. The natural history of actinic keratosis: a systematic review. Br J Dermatol. 2013 Sep;169(3):502-18. doi: 10.1111/bjd.12420. 

Authors

  • Erik P. Schwarz