The content of this evidence summary was up-to-date in March 2013. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.
Ingenol mebutate gel (Picato) is a macrocyclic diterpene ester licensed for the cutaneous treatment of non-hyperkeratotic, non-hypertrophic actinic keratosis in adults. It received a European marketing authorisation in November 2012 and was launched in the UK in January 2013.
Guidance on actinic keratosis from the British Association of Dermatologists, the European Dermatology Forum and the Primary Care Dermatology Society pre-dates the availability of ingenol mebutate gel. Depending on clinical presentation, treatment of actinic keratosis may be targeted at individual lesions, or field-directed treatment may be used for larger areas of skin with multiple lesions. Therapies include ablative procedures, photodynamic therapy and a number of topical treatments.
Ingenol mebutate gel is a patient-applied, topical, field-directed treatment for actinic keratosis. Two strengths are licensed: 150 micrograms/gram (0.015%) for treating lesions of the face or scalp, and 500 micrograms/gram (0.05%) for treating the trunk or extremities. The duration of the treatment course, which is a once-daily application for 2 consecutive days for the trunk or extremities, and once daily for 3 consecutive days for the face or scalp, is shorter than that for other patient-applied, topical medicines licensed for this condition.
In 4 phase III, double-blind, randomised, vehicle-gel controlled trials of patients with actinic keratosis, ingenol mebutate gel was associated with significantly higher rates of complete lesion clearance in the treatment area, compared with vehicle gel. In pooled analyses of these studies, the percentages of patients with complete clearance of lesions after treatment with ingenol mebutate gel were 42.2% (face/scalp studies) and 34.1% (trunk/extremities studies), compared with 3.7% and 4.7% respectively of patients receiving vehicle gel (p<0.001 in both cases).
The most common treatment-related adverse events reported in the phase III studies were skin responses at the site of application.
Local decision makers will need to consider the place of ingenol mebutate gel alongside other available treatments for actinic keratosis. The publication of direct head-to-head studies with other treatments would enable its place in therapy to be more clearly established. The authors of a 2012 Cochrane review concluded that field-directed treatments for actinic keratosis, which included ingenol mebutate gel, had similar efficacy. However, adverse events and cosmetic outcomes varied, and more direct comparisons between treatments are needed to determine optimal therapeutic approaches.
Lebwohl M, Swanson N, Anderson LL et al. (2012) Ingenol mebutate gel for actinic keratosis. New England Journal of Medicine 366: 1010–19
'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.