Clinical trial NCT04202445: TreatMent of ActInic KerAtosis Lesions : pharmacoepiDemiological Study of the Impact in Real Life of ingenOl Mebutate Gel (Picato®) on Patients Satisfaction
Official title: TreatMent of ActInic KerAtosis Lesions : pharmacoepiDemiological Study of the Impact in Real Life of ingenOl Mebutate Gel (Picato®) on Patients Satisfaction
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Actinic Keratosis
Keywords: Actinic keratosis
Field treatment
Ingenol mebutate
Picato
Mikado
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2019-12-17
Enrollment: 1218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients diagnosed with actinic keratosis planned to receive treatment with ingenol mebutate at the discretion of the dermatologist

Brief summary: This is an observational longitudinal study, prospective, multicenter, performed in metropolitan France, on a representative sample of dermatologists.

Data will be collected by physicians during 2 or 3 visits (according to their usual practice), from the patient file, questioning and clinical examination performed during these visits.

Data about the patient's perception (satisfaction, perception of local skin reactions, quality of life) will be collected directly by the patient using self-administered questionnaires at inclusion visit, day 7 and 2 months later.

Detailed description: Actinic keratosis (AKs) are common skin diseases affecting areas previously overexposed to the sun (in particular face, nape of the neck, hands). They affect mainly elderly people (mean age: 74 years old, with 97% who are over 50 years old) and preferably men (60%). In Europe, prevalence of AK in the adult population over 40 years is estimated to be between 6% and 25%.

Subjects at risk are light-skinned people (phototype I and II according to Fitzpatrick scale) with high cumulative sun exposure or phototherapy. Over 80% of patients have a light phototype and 37% of patients with AK have an outside professional activity.

Diagnosis of AK is usually clinical, during skin examination which is recommended for any physician's visit. There are often multiple lesions, some of which, in the absence of effective treatment, can progress to squamous cell carcinoma (0.025% to 20% per year/lesion).

Although the evolution rate of AKs to carcinoma remains low and disappearance or sole persistence of the lesion is possible, their evolution is unpredictable, and it is therefore recommended to monitor and treat the AKs.

Treatment options include cryotherapy, topical treatments, photodynamic therapy, vaporization of lesions by CO2 laser or electrocoagulation and curretage.

When there are few AK lesions, which are localized and with superficial forms, cryotherapy is the reference treatment (it is widely used by dermatologists, as it is simple, fast and does not require special equipment), whereas topical treatment (5-FU, imiquimod, diclofenac) is recommended in case of multiple keratosis or lesions on a larger area of the skin. The disadvantage of cryotherapy and photodynamic therapy is that these techniques can be painful and lead to depigmentation or scarring. Topical treatments which are available (imiquimod, 5-FU, diclofenac) may induce severe inflammatory reactions sometimes responsible for premature termination and thus ineffective.

Combined with their length (4 to 16 weeks), the complexity of current topical regimens would be the cause of poor compliance.

So, all dermatologists agree with the need to shorten duration of treatment and reduce the number of applications. Ingenol mebutate gel (Picato®), used in very short 2-3 days cycle, with one application per day, meets this need.

Development of ingenol mebutate gel included 4 pivotal phase III trials, evaluating its efficacy and safety. The results of these studies have established satisfactory efficacy and safety for Picato® with, on one hand, proven efficacy after two months for face, scalp, trunk and extremities and, on the other hand, transient local skin reactions (erythema, flaking/scaling, crusting,swelling,...), which appear early, peak in intensity after the end of treatment (day 3 or day 4) and disappear without sequelae within 2-4 weeks after application of the gel. At day 57, mean patient global satisfaction scores, either assessed with TSQM or Skindex-16, were statistically higher in the ingenol mebutate gel group than in the vehicle group. In a long term follow up study, ingenol mebutate produced clinically relevant sustained clearance and long-term lesion reduction.

These characteristics are a potentially important advantage for treatment compliance as well as for patient comfort.

Eligibility criteria: Inclusion Criteria:

* Patient at least 18 years old, seen by the dermatologist during a consultation, whether actinic keratosis is the reason for consultation or not.
* Patient with AK lesions and for whom the dermatologist decided to initiate a treatment with Picato®\* 150 or Picato®\* 500
* Patient informed and accepting the automatic processing of medical data \* To respect the physicians' independence, this study is conducted among patients for whom the decision of therapeutic care is not related to their inclusion.

Exclusion Criteria:

* Patient with a contraindication to treatment with Picato®.
* Patient unable to read and/or to understand a self-administered questionnaire.
* Patient already included in the study.
* Patient participating or having participated in the previous month in a clinical trial in dermatology.

Primary outcomes:
measure: Treatment Satisfaction Questionnaire of Medication (TSQM-9)
timeFrame: 2 months after end of treatment
Secondary outcomes:
measure: Dermatology Life Quality Index - DLQI
timeFrame: Baseline and 2 months after end of treatment
measure: Real-life efficacy of Picato
timeFrame: Between Day 1 after the treatment application and 12 months (maximum 2 follow-up visits after the inclusion)
Other outcomes:
Locations:
Study officials:
affiliation: LEO Pharma
name: Sarah Moumane, MD
role: STUDY_CHAIR
References:
citation: Frost CA, Green AC. Epidemiology of solar keratoses. Br J Dermatol. 1994 Oct;131(4):455-64. doi: 10.1111/j.1365-2133.1994.tb08544.x.
citation: Memon AA, Tomenson JA, Bothwell J, Friedmann PS. Prevalence of solar damage and actinic keratosis in a Merseyside population. Br J Dermatol. 2000 Jun;142(6):1154-9. doi: 10.1046/j.1365-2133.2000.03541.x.
citation: Quaedvlieg PJ, Tirsi E, Thissen MR, Krekels GA. Actinic keratosis: how to differentiate the good from the bad ones? Eur J Dermatol. 2006 Jul-Aug;16(4):335-9.
citation: Dinehart SM. The treatment of actinic keratoses. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):25-8. doi: 10.1067/mjd.2000.103338.
citation: French Society of Dermatology. [Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma and precursor lesions. Arguments - May 2009]. Ann Dermatol Venereol. 2009 Sep;136 Suppl 5:S189-242. No abstract available. French.
citation: Thai KE, Fergin P, Freeman M, Vinciullo C, Francis D, Spelman L, Murrell D, Anderson C, Weightman W, Reid C, Watson A, Foley P. A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol. 2004 Sep;43(9):687-92. doi: 10.1111/j.1365-4632.2004.02056.x.
citation: Burge SM, Bristol M, Millard PR, Dawber RP. Pigment changes in human skin after cryotherapy. Cryobiology. 1986 Oct;23(5):422-32. doi: 10.1016/0011-2240(86)90027-1.
citation: Zouboulis CC. Cryosurgery in dermatology. Eur J Dermatol. 1998 Oct-Nov;8(7):466-74.
citation: Fu W, Cockerell CJ. The actinic (solar) keratosis: a 21st-century perspective. Arch Dermatol. 2003 Jan;139(1):66-70. doi: 10.1001/archderm.139.1.66. No abstract available.
citation: Lebwohl M, Swanson N, Anderson LL, Melgaard A, Xu Z, Berman B. Ingenol mebutate gel for actinic keratosis. N Engl J Med. 2012 Mar 15;366(11):1010-9. doi: 10.1056/NEJMoa1111170.
citation: Anderson L, Schmieder GJ, Werschler WP, Tschen EH, Ling MR, Stough DB, Katsamas J. Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis. J Am Acad Dermatol. 2009 Jun;60(6):934-43. doi: 10.1016/j.jaad.2009.01.008.
citation: Berman B. New developments in the treatment of actinic keratosis: focus on ingenol mebutate gel. Clin Cosmet Investig Dermatol. 2012;5:111-22. doi: 10.2147/CCID.S28905. Epub 2012 Aug 24.