Treatment of AKs is essential, as these pre-cancerous lesions can progress to squamous cell carcinomas.3,4 Historically, treatment of AKs had been lesion-directed, with destructive modalities like liquid nitrogen and electrodesiccation and curettage considered mainstays of treatment just over two decades ago.5
Somewhat recently, our conception of AKs has shifted from a focus on individual lesions to recognition that the presence of AKs is a manifestation of field cancerization.6 Therapeutic strategies, therefore, have evolved to emphasize the treatment of both clinically visible and subclinical lesions.5 The notion of field-directed therapy has been facilitated by the availability of numerous topical formulations now FDA-approved for the treatment of AKs.
As noted by Rajkumar and Armstrong in the pages ahead, five different drug compounds are FDA-approved to treat AKs. Despite differences in phase 3, pivotal trial designs and outcome measures, these agents are all considered efficacious for the treatment of AKs. Similarly, as Rajkumar and Armstrong conclude, the available drugs are generally considered safe when used as directed. However, they note, there is great variability in tolerability.
Tolerability is a crucial consideration when it comes to therapy directed at field cancerization, especially that AKs are chronic and recurring lesions and require life-long treatment. Furthermore, prolonged and severe local skin reactions, especially on the face and scalp, may disrupt daily living activities, social engagements, and negatively impact the quality of life. If patients reduce the frequency or amount of drug application or cut short the duration of treatment due to poor tolerability, the effectivness will be compromised.
The newest topical drug approved for the management of AKs, tirbanibulin, may offer distinct advantages in terms of tolerability and treatment duration, perhaps as a consequence of its unique mechanism of action. As opposed to earlier drugs that induced necrosis, tirbanibulin induces apoptosis. In clinical trials, most local skin reactions (LSRs) associated with tirbanibulin were mild to moderate, and fewer than 10% of patients reported severe LSRs.7 Of note, no patients in the clinical trials discontinued therapy; treatment was applied once daily for five days.
Selection of an appropriate treatment for management of AKs depends on multiple factors, including but not limited to patient age, lifestyle, extent of actinic damage, and history of UV exposure. The availability of multiple safe and effective treatments provides options for dermatologists to tailor treatment to the individual needs of their patients. The best outcomes will be achieved with a patient-centric approach along with more tolerable topical treatment.8 With recent advancements in topical treatment, including the introduction of tirbanibulin, a new chemical entity with established efficacy and favorable tolerability profile, dermatologists may yet improve patient experiences and subsequently adherence and outcomes in field-directed management of AKs.
LHK has received compensation from JDD for his editorial support and has served as either consultant, speaker, investigator, or advisory board member for Almirall, Leo Pharma, and Ortho Dermatologics.
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