Introduction

Ingenol mebutate (trade name: Picato) gel has been approved in Germany since November 2012 for the treatment of certain types of actinic keratosis in adults.

Actinic keratosis is a skin disease in which the uppermost layer of skin hardens and gradually becomes thick and scaly (callused). It develops from frequent exposure of skin cells called keratinocytes to intense UV radiation, which causes them to change (mutate) and multiply. Skin on the face, arms and legs, neck and back is most vulnerable. In up to 10 out of 100 people, this condition can develop into a type of skin cancer called squamous cell carcinoma.

There are different types of actinic keratosis, which vary depending on how thick and scaly the affected area of skin is. Ingenol mebutate has been approved for the treatment of actinic keratosis where the skin has stayed flat and is not too callused – referred to as non-hyperkeratotic and non-hypertrophic actinic keratosis. Skin affected by these types of keratosis can turn rough and scaly.

Ingenol mebutate is supposed to kill off the affected skin cells and prevent inflammation. It is not known exactly how it works.

Application

Ingenol mebutate is applied to the skin as a gel. The gel is available in two different doses: 150 or 500 micrograms of ingenol mebutate per gram of gel. One tube (of either dose) is enough to treat a 5 cm by 5 cm patch of skin.

The lower dose is used when treating the scalp or facial skin. The skin is treated for three consecutive days using one tube per day.

The higher dose is used for treating skin on other parts of the body, like the limbs or back. This dose is applied to the affected areas for two consecutive days, using one tube for each area per day.

Other treatments

The standard treatment options for people with non-hyperkeratotic and non-hypertrophic actinic keratosis are diclofenac and hyaluronic acid gel or 5-fluorouracil cream for applying to the skin. If only a few areas of skin are affected, a surgical treatment that uses extreme cold (cryotherapy) may also be an option.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into whether ingenol mebutate has any advantages or disadvantages when compared with the standard treatment for adults with non-hyperkeratotic and non-hypertrophic actinic keratosis.
The manufacturer provided one study on this issue involving 502 people. 255 of the patients were given treatment with ingenol mebutate, and the remaining 247 received the diclofenac and hyaluronic acid treatment. All of the patients in the study only had actinic keratosis on their face or scalp. Each participant had an average (median) of six areas of affected skin when the study was started. These were the results after 17 weeks:

What are the advantages of ingenol mebutate?

Complete improvement of actinic keratosis: Early results suggest that ingenol mebutate has an advantage here when compared with the diclofenac and hyaluronic acid treatment. In 45 out of 100 people who used ingenol mebutate, the visible patches of actinic keratosis disappeared completely. This happened in 24 out of 100 people who had the diclofenac and hyaluronic acid treatment. It is still unclear how long the effect lasts.

What are the disadvantages of ingenol mebutate?

No disadvantages were found.

No differences

  • Serious side effects: About 4 out of 100 people in each group had severe side effects.
  • Skin reactions to the treatment: There were no differences here either. Each treatment caused a skin reaction in 19 to 24 out of 100 people.

What remains unanswered?

The manufacturer provided no suitable data on the following:

  • Development of squamous cell carcinoma
  • Health-related quality of life

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the "early benefit assessment of medications." On the basis of this review and the hearings received, the G-BA passed a resolution on the added benefit of ingenol mebutate (Picato).