Actinic Keratosis — SCE Dermatology MCQ

Correct answer: E — Post-marketing safety signal — increased incidence of skin cancer in treated areas compared to vehicle

The correct answer is E, post-marketing safety signal, increased incidence of skin cancer in treated areas compared to vehicle. Ingenol mebutate (Picato) was licensed for field treatment of actinic keratosis, but pharmacovigilance data including a 3 year comparative study and a vehicle-controlled trial showed significantly more skin malignancies, particularly squamous cell carcinoma, in ingenol mebutate treated skin than in comparator or vehicle treated skin. This safety signal led the MHRA to issue a class 2 recall in January 2020 and the EMA's PRAC to recommend suspension of the marketing authorisation as a precaution. The mechanism relates to concerns that the drug's cytotoxic, inflammation-inducing action on keratinocytes may promote rather than simply clear dysplastic clones, tipping the benefit-risk balance unfavourably despite prior awareness of a theoretical risk at licensing. Why the other options are wrong: C. Manufacturing issues: the withdrawal was driven by clinical safety data from comparative and vehicle-controlled trials, not by any defect in production or quality control of the gel. D. Severe pain on application only: local skin reactions and application site pain were known, expected, and labelled side effects from launch; they did not trigger the 2020 suspension, which was specifically about malignancy risk. B. Cost only: cost was never cited by the MHRA or EMA as a reason; the regulatory action was a precautionary safety measure following pharmacovigilance review. A. Inefficacy: ingenol mebutate was effective at clearing actinic keratoses in trials; efficacy was never in question, only the balance of that benefit against an increased cancer risk in treated skin. Key point: Ingenol mebutate was withdrawn because post-marketing and trial data showed a higher rate of skin cancer (especially SCC) in treated areas than with vehicle or comparator, not because of pain, cost, manufacturing, or lack of efficacy.

Reference: GOV.UK / MHRA Drug Safety Update: 'Ingenol mebutate gel (Picato): increased incidence of skin tumours seen in some clinical studies' and subsequent EMA PRAC suspension notice (2019-2020). https://www.gov.uk/drug-safety-update/ingenol-mebutate-gel-picato-increased-incidence-of-skin-tumours-seen-in-some-clinical-studies