A New Intervention for Actinic Keratoses: Ingenol Mebutate Gel

Source: Rosen RH, et al. J Am Acad Dermatol 2012;66:486-493.

Actinic keratoses (ak) is biologically in situ squamous cell carcinoma, with the potential to become invasive in a minority of cases. However, because an individual patient may have many AK and it is not possible with certainty to identify which lesions are more likely to progress, it has been recommended that removal of AK be performed whenever possible. In the primary care setting, the three most prominent methods of destruction are cryotherapy, immune activators (e.g., imiquimod cream), and antimetabolites (e.g., 5-fluorouracil cream). Each of these methods has substantial limitations; for instance, the inflammatory response to appropriate use of imiquimod or 5-fluorouracil may be both painful and (at least transiently) cosmetically unwieldy. Additionally, traditional regimens of commonly used topicals require multiple applications over several weeks or more.

Ingenol mebutate (ING) is a recently approved topical agent that works by induction of lesion necrosis as well as by activation of antibody-directed cellular cytotoxic pathways. What this does for AK is produce a prompt and immediate kill effect on abnormal cells (within a few hours), which is coupled with a drug-mediated activation of B-cells that binds to abnormal (precancerous) cells over subsequent days and destroys them. This dual mechanism provides for short treatment regimens (2-3 days), with persistent post-treatment effects that obliterate evolving AK. The tolerability profile of ingenol, coupled with its dual mechanism of action and ease of administration, may give it a priority role in topical therapies for AK, although the clearance rates with the new product are not yet established to be at parity with older agents until head-to-head comparator trials are performed.