To sum up, despite the efforts made, it still seems necessary to
try to establish changes in the main endpoints for assessing AK
lesions and their underlying area, as well as in the evaluation
of the efficacy of treatments, that can address the intrinsic
limitation of the mismatch between clinical studies and actual
practice (ie, using complete clearance as the main endpoint
in clinical studies vs significant improvement in practice). We
also suggest avoiding applying classifications such as the Olsen
grading system, which do not improve routine clinical practice
and appropriate treatment selection.
DISCLOSURES
LS and PB received honoraria from Almirall, Beiersdorf,
Biofrontera, Galderma, Mylan, and Sanofi Genzyme. LS, PB and
AB have participated in clinical advisory boards for Almirall.
Almirall S.A. supported this work.
ACKNOWLEDGMENT
Editorial assistance and writing support were provided by
Mònica Giménez PhD and Eva Mateu PhD of TFS HealthScience.
REFERENCES
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8. Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol. 2019;94(6):637-657.
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15. Heppt MV, Leiter U, Steeb T, et al. S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma – short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators. J Dtsch Dermatol Ges. 2020;18(3):275-294.
16. Bonerandi JJ, Beauvillain C, Caquant L, et al. Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad Dermatol Venereol. 2011;25 Suppl 5:1-51.
17. Richard MA, Amici JM, Basset-Seguin N, et al. Management of actinic keratosis at specific body sites in patients at high risk of carcinoma lesions: expert consensus from the AKTeamTM of expert clinicians. J Eur Acad Dermatol Venereol. 2018;32(3):339-346.
18. Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL. Clinical implications and utility of field cancerization. Cancer Cell Int. 2007;7:2.
19. Epstein E. Quantifying actinic keratosis. Am J Clin Dermatol. 2004;5(3):141-144.
20. Lee K, Lew R, Weinstock M. Improvement in precision of counting actinic keratoses. Br J Dermatol. 2014;170(1):188-191.
21. Weinstock MA, Bingham SF, Cole GW, et al. Reliability of counting actinic keratoses before and after brief consensus discussion: the VA topical tretinoin chemoprevention (VATTC) trial. Arch Dermatol. 2001;137(8):1055-1058.
22. Röwert-Huber J, Patel MJ, Forschner T, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol. 2007;156 Suppl 3:8-12.
23. Schmitz L, Kahl P, Majores M, et al. Actinic keratosis: correlation between clinical and histological classification systems. J Eur Acad Dermatol Venereol. 2016;30(8):1303-1307.
24. Dirschka T, Pellacani G, Micali G, et al. A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index. J Eur Acad Dermatol Venereol. 2017;31(8):1295-1302.
25. Figueras Nart I, Cerio R, Dirschka T, et al. Defining the actinic keratosis field: a literature review and discussion. J Eur Acad Dermatol Venereol. 2018;32(4):544-563.
26. Fernandez Figueras MT. From actinic keratosis to squamous cell carcinoma: pathophysiology revisited. J Eur Acad Dermatol Venereol. 2017;31 Suppl 2:5-7.
27. Dréno B, Cerio R, Dirschka T, et al. A novel actinic keratosis field assessment scale for grading actinic keratosis disease severity. Acta Derm Venereol. 2017;97(9):1108-1113.
28. Reynolds KA, Schlessinger DI, Vasic J, et al. Core outcome set for actinic keratosis clinical trials. JAMA Dermatol. 2020;156(3):326-333.
29. Center for drug evaluation and research approval package for: application number: 213189Orig1s000. Available at: https://www.accessdata.fda. gov/drugsatfda_docs/nda/2020/213189Orig1s000Approv.pdf. Accessed November 15, 2021.
30. Kempers S, DuBois J, Forman S, et al. Tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. J Drugs Dermatol. 2020;19(11):1093-1100.
31. European Medicines Agency (EMA). Summary of opinion (initial authorisation) Klisyri – tirbanibulin. Available at: https://www.ema.europa.eu/ en/documents/smop-initial/chmp-summary-positive-opinion-klisyri_en.pdf. Accessed November 15, 2021.
32. Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of Tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384(6):512-520.
33. Berman B, Goldenberg G, Hanke CW, et al. Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11- week results. J Drugs Dermatol. 2014;13(2):154-160.
34. Ulrich M, Reinhold U, Skov T, et al. Histological examination confirms clinical clearance of actinic keratoses following treatment with ingenol mebutate 0·05% gel. Br J Dermatol. 2017;176(1):71-80.
35. Schmitz L, Gambichler T, Gupta G, et al. Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2018;32(5):752-756.
36. del Alcázar Viladomiu E, Lamas Doménech N, Salleras Redonnet M. Absolute versus relative Psoriasis Area and Severity Index in clinical practice. Actas Dermosifiliogr. (Engl Ed). 2019;110(7):606-610.
37. Norlin JM, Nilsson K, Persson U, Schmitt-Egenolf M. Complete skin clearance and Psoriasis Area and Severity Index response rates in clinical practice: predictors, health-related quality of life improvements and implications for treatment goals. Br J Dermatol. 2020;182(4):965-973.
38. Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis. 2005;64 Suppl 2(Suppl 2):ii65-ii73.
39. Wechter T, Heath M, Aung-Din D, et al. Current psoriasis efficacy outcome measures in clinical trials. Curr Dermatol Rep. 2018;7:261-268.
2. Rosen T, Lebwohl MG. Prevalence and awareness of actinic keratosis: barriers and opportunities. J Am Acad Dermatol. 2013;68(1 Suppl 1):S2-S9.
3. Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000;142(6):1154-1159.
4. Roewert-Huber J, Stockfleth E, Kerl H. Pathology and pathobiology of actinic (solar) keratosis – an update. Br J Dermatol. 2007;157 Suppl 2:18-20.
5. Coleman NM. Actinic keratosis pathology: overview, etiology, clinical features. Available at: https://emedicine.medscape.com/article/1976538- overview. Accessed October 13, 2021.
6. Cerio R, Dirschka T, Dréno B, et al. Actinic keratosis, a chronic, progressive disease: understanding clinical gaps to optimize patient management. Acta Derm Venereol. 2017;97(8):997-998.
7. Dirschka T, Gupta G, Micali G, et al. Real-world approach to actinic keratosis management: practical treatment algorithm for office-based dermatology. J Dermatolog Treat. 2017;28(5):431-442.
8. Reinehr CPH, Bakos RM. Actinic keratoses: review of clinical, dermoscopic, and therapeutic aspects. An Bras Dermatol. 2019;94(6):637-657.
9. Siegel JA, Korgavkar K, Weinstock MA. Current perspective on actinic keratosis: a review. Br J Dermatol. 2017;177(2):350-358.
10. Olsen EA, Abernethy ML, Kulp-Shorten C, et al. A double-blind, vehiclecontrolled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck. J Am Acad Dermatol. 1991;24(5 Pt 1):738-743.
11. Peris K, Calzavara-Pinton PG, Neri L, et al. Italian expert consensus for the management of actinic keratosis in immunocompetent patients. J Eur Acad Dermatol Venereol. 2016;30(7):1077-1084.
12. Werner RN, Stockfleth E, Connolly SM, et al. Evidence- and consensus-based (S3) guidelines for the treatment of actinic keratosis – International League of Dermatological Societies in cooperation with the European Dermatology Forum – Short version. J Eur Acad Dermatol Venereol. 2015;29(11):2069- 2079.
13. Ferrándiz C, Fonseca-Capdevila E, GarcÃa-Diez A, et al. Spanish adaptation of the European guidelines for the evaluation and treatment of actinic keratosis. Actas Dermo-Sifiliográficas (English Edition). 2014;105(4):378-393.
14. Hofbauer GF, Anliker M, Boehncke WH, et al. Swiss clinical practice guidelines on field cancerization of the skin. Swiss Med Wkly. 2014;144:w14026.
15. Heppt MV, Leiter U, Steeb T, et al. S3 guideline for actinic keratosis and cutaneous squamous cell carcinoma – short version, part 1: diagnosis, interventions for actinic keratoses, care structures and quality-of-care indicators. J Dtsch Dermatol Ges. 2020;18(3):275-294.
16. Bonerandi JJ, Beauvillain C, Caquant L, et al. Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. J Eur Acad Dermatol Venereol. 2011;25 Suppl 5:1-51.
17. Richard MA, Amici JM, Basset-Seguin N, et al. Management of actinic keratosis at specific body sites in patients at high risk of carcinoma lesions: expert consensus from the AKTeamTM of expert clinicians. J Eur Acad Dermatol Venereol. 2018;32(3):339-346.
18. Dakubo GD, Jakupciak JP, Birch-Machin MA, Parr RL. Clinical implications and utility of field cancerization. Cancer Cell Int. 2007;7:2.
19. Epstein E. Quantifying actinic keratosis. Am J Clin Dermatol. 2004;5(3):141-144.
20. Lee K, Lew R, Weinstock M. Improvement in precision of counting actinic keratoses. Br J Dermatol. 2014;170(1):188-191.
21. Weinstock MA, Bingham SF, Cole GW, et al. Reliability of counting actinic keratoses before and after brief consensus discussion: the VA topical tretinoin chemoprevention (VATTC) trial. Arch Dermatol. 2001;137(8):1055-1058.
22. Röwert-Huber J, Patel MJ, Forschner T, et al. Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification. Br J Dermatol. 2007;156 Suppl 3:8-12.
23. Schmitz L, Kahl P, Majores M, et al. Actinic keratosis: correlation between clinical and histological classification systems. J Eur Acad Dermatol Venereol. 2016;30(8):1303-1307.
24. Dirschka T, Pellacani G, Micali G, et al. A proposed scoring system for assessing the severity of actinic keratosis on the head: actinic keratosis area and severity index. J Eur Acad Dermatol Venereol. 2017;31(8):1295-1302.
25. Figueras Nart I, Cerio R, Dirschka T, et al. Defining the actinic keratosis field: a literature review and discussion. J Eur Acad Dermatol Venereol. 2018;32(4):544-563.
26. Fernandez Figueras MT. From actinic keratosis to squamous cell carcinoma: pathophysiology revisited. J Eur Acad Dermatol Venereol. 2017;31 Suppl 2:5-7.
27. Dréno B, Cerio R, Dirschka T, et al. A novel actinic keratosis field assessment scale for grading actinic keratosis disease severity. Acta Derm Venereol. 2017;97(9):1108-1113.
28. Reynolds KA, Schlessinger DI, Vasic J, et al. Core outcome set for actinic keratosis clinical trials. JAMA Dermatol. 2020;156(3):326-333.
29. Center for drug evaluation and research approval package for: application number: 213189Orig1s000. Available at: https://www.accessdata.fda. gov/drugsatfda_docs/nda/2020/213189Orig1s000Approv.pdf. Accessed November 15, 2021.
30. Kempers S, DuBois J, Forman S, et al. Tirbanibulin ointment 1% as a novel treatment for actinic keratosis: phase 1 and 2 results. J Drugs Dermatol. 2020;19(11):1093-1100.
31. European Medicines Agency (EMA). Summary of opinion (initial authorisation) Klisyri – tirbanibulin. Available at: https://www.ema.europa.eu/ en/documents/smop-initial/chmp-summary-positive-opinion-klisyri_en.pdf. Accessed November 15, 2021.
32. Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of Tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384(6):512-520.
33. Berman B, Goldenberg G, Hanke CW, et al. Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11- week results. J Drugs Dermatol. 2014;13(2):154-160.
34. Ulrich M, Reinhold U, Skov T, et al. Histological examination confirms clinical clearance of actinic keratoses following treatment with ingenol mebutate 0·05% gel. Br J Dermatol. 2017;176(1):71-80.
35. Schmitz L, Gambichler T, Gupta G, et al. Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma. J Eur Acad Dermatol Venereol. 2018;32(5):752-756.
36. del Alcázar Viladomiu E, Lamas Doménech N, Salleras Redonnet M. Absolute versus relative Psoriasis Area and Severity Index in clinical practice. Actas Dermosifiliogr. (Engl Ed). 2019;110(7):606-610.
37. Norlin JM, Nilsson K, Persson U, Schmitt-Egenolf M. Complete skin clearance and Psoriasis Area and Severity Index response rates in clinical practice: predictors, health-related quality of life improvements and implications for treatment goals. Br J Dermatol. 2020;182(4):965-973.
38. Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis. 2005;64 Suppl 2(Suppl 2):ii65-ii73.
39. Wechter T, Heath M, Aung-Din D, et al. Current psoriasis efficacy outcome measures in clinical trials. Curr Dermatol Rep. 2018;7:261-268.
AUTHOR CORRESPONDENCE
Lutz Schmitz MD l.schmitz@centroderm.de
