Pharmacokinetic and pharmacodynamic evaluation of ingenol mebutate for the treatment of actinic keratosis

ABSTRACT

Introduction: Actinic keratosis (AK) is a common skin condition that results from exposure to chronic ultraviolet (UV) radiation. AK is characterized by visible, scaly lesions; sub-clinical lesions may also be present within a field of UV-exposed skin. These lesions exist on a disease continuum with squamous cell carcinoma. Field therapies, such as ingenol mebutate, aim to treat the visible and sub-clinical lesions within an area of sun-damaged skin.

Areas covered: According to the SmPC, ingenol mebutate has a proposed dual mechanism of action that induces cell death necrosis with the production of a local pro-inflammatory response and stimulation of apoptosis. In clinical trials, efficacy of ingenol mebutate has been shown through clearance of AK lesions. Adverse events and local skin responses generally resolved within 2–4 weeks from the end of treatment, depending on body location.

Expert opinion: AK can be treated using lesion-directed or topical therapies. Topical treatment with ingenol mebutate has been shown to have superior efficacy compared with diclofenac/sodium hyaluronate. The short and simple treatment regimen may improve patient adherence to ingenol mebutate and satisfaction with treatment. It might be worth evaluating further indications for ingenol mebutate including treatment of basal cell carcinoma.

KEYWORDS:

• Actinic keratosis
• field cancerization
• sub-clinical AK lesions
• ingenol mebutate

Declaration of interest

E Stockfteth has received fees from LEO Pharma, Pierre Fabre and Almirall for other work. Mike Bastian is an employee of LEO Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has undertaken studies and given talks for Leo Pharma. Peer reviewers have no other relevant financial relationships to disclose.

Additional information

Funding

This paper was funded by LEO Pharma.