INTRODUCTION
Actinic keratosis (AK) is a common skin lesion that develops due to long-term sun exposure. AKs are estimated to affect 14% of the global population.1 Factors that increase the risk of developing AKs include male sex, older age, lighter skin color, red hair, and immunocompromise.2 Clinically, AKs present as poorly demarcated, scaly areas with variable keratosis that may cause symptomatic or cosmetic discomfort.3 However, the primary clinical significance of AKs is their potential for malignancy. AKs are characterized by atypia of keratinocytes,3 and untreated lesions can progress to squamous cell carcinomas (SCCs) at a rate of 0.025% to 16% per year.4 Therefore, treatment of all AKs is recommended.2
AK therapies can be categorized as lesion- or field-directed. Lesion-directed therapies target singular AK lesions for individuals with low disease burden and include cryotherapy and excisions.3 In contrast, field-directed therapies target larger areas with multiple AKs and subclinical lesions for individuals with high disease burden. Field-directed therapies include photodynamic therapy and topical treatments such as imiquimod, 5-fluorouracil, and diclofenac sodium.3 Although various field-directed therapies exist, they are often associated with prolonged treatment duration (ie, 12 or 16 weeks), frequent use (ie, twice daily), and prolonged inflammation.2 These barriers limit patient adherence to many field-directed therapies.
Tirbanibulin 1% ointment is a field-directed therapy for AKs that gained initial approval from the United States Food and Drug Administration (FDA) in 2020.5 Tirbanibulin inhibits microtubules and blocks Src kinase signaling, resulting in antiproliferative and proapoptotic effects.6,7 Compared to other field-directed therapies, tirbanibulin is administered with lower frequency and treatment duration, with once-daily application for 5 consecutive days over a treatment area of up to 25 cm2.5 Additionally, tirbanibulin has been investigated and approved by the FDA in 2024 for larger treatment areas of up to 100 cm2.8 In this paper, we aim to review the efficacy, safety, tolerability, and clinical outcomes of tirbanibulin 1% ointment from clinical trials and real-world clinical studies.
Phase 1 and 2 Trials
A phase 1 trial assessed the safety and efficacy of tirbanibulin 1% ointment for AKs on the dorsal forearm across 4 different cohorts.6 The cohorts varied in treatment dosage (50 vs 200 mg/day), treatment duration (3 vs 5 days), and surface area of application (25 vs 100 cm2). Patients with 4 to 8 AK lesions received treatment over an area of 25 cm2, whereas patients with 8 to 16 AK lesions received treatment over an area of 100
