Investigation of the Efficacy and Tolerability of Topical Applied Tirbanibulin on Actinic Keratoses With Downward-directed Proliferation Patterns

Actinic keratoses (AK) are premalignant skin changes of a cutaneous squamous cell carcinoma (SCC), which are often triggered by UV exposure. Clinically, they appear as small, rough, reddish, sandpaper-like patches, occasionally also as hyperkeratotic lesions. They are one of the most common reasons for dermatological consultations, and their incidence has been steadily increasing in recent years due to changes in leisure habits with increased UV exposure and demographic changes in the population, such as those observed in Germany.

While the mortality rate of squamous cell carcinoma of the skin is low, the persistence and recurrence of AK, which requires frequent treatment, is a challenge for both patients and healthcare systems.

There are numerous treatment options for AK, ranging from surgical and cryosurgical interventions to ablative laser treatments, topical and photodynamic therapies. These treatments can generally be categorized as lesion- or field-oriented.

Some AK show resistance to conventional therapies. This could possibly be due to different proliferation patterns of AK. Schmitz et al. established the PRO score, an instrument that describes the proliferation behavior of AK in a three-stage scale. This histological score is well validated and is increasingly used in histological diagnostics. New imaging techniques such as confocal line-field optical coherence tomography (LC-OCT) enable real-time assessment of histological parameters without the need for biopsies. In LC-OCT it is possible to detect the PRO Score of an AK in a few seconds.

Clinical parameters such as the Olsen grade, on the other hand, record the visible or palpable hyperkeratosis of an AK. However, the significance of hyperkeratosis for the risk of progression of AK to SCC is only of minor importance. Histological diagnostics and LC-OCT therefore make it possible to determine this risk more precisely.

Similarly, clinical scores such as the Olsen garde do not indicate which AKs are refractory to therapy, and which respond to therapy. One reason for this could be the proliferation behavior of the individual AK. Tirbanibulin, which primarily targets this cell proliferation, is a promising agent for the treatment of highly proliferative AK (PRO II and III). One aim is to observe its effects on basal proliferation after treatment, which can be assessed in real time using LC-OCT. This non-invasive method provides rapid evaluations within minutes. In addition to efficacy in proliferative AK, evaluation of the tolerability of tirbanibulin is crucial to contextualize its role in therapy. It is therefore of interest to determine whether increased skin reactions in proliferative AK correlate with improved clearance rates.

Tirbanibulin is a method frequently used in practice for the treatment of actinic keratoses. The application is quick with only 5 consecutive applications, results in only a minor local reaction and is nevertheless effective. In this study, various parameters such as local tolerance, the Olsen grade and the PRO score will be monitored using LC-OCT. Patients with clinically confirmed AK for whom in-label therapy with tirbanibulin is planned anyway will be included.

• Clinical clearance of marker lesion at visit 2 [Срок оценки: 14 days after baseline visit]
• Clinical clearance of marker lesion at visit 3 [Срок оценки: 70 days after baseline]
• Improvement of PRO Score at V2 [Срок оценки: 14 days after baseline]
• LC-OCT clearance of marker lesion at V2 [Срок оценки: 14 days after baseline]
• Histopathological clearance of marker lesion at V3 [Срок оценки: 70 days after baseline]