After eight weeks, lesions had completely cleared in more people receiving the active treatment compared to those receiving placebo (see Table). For one patient with face and scalp lesions to have complete resolution, 2.6 patients needed to be treated. For patients with trunk and extremity lesions, the number needed to treat was 3.4.
Patients whose lesions had resolved after eight weeks were enrolled in observational follow-up studies. After 12 months, actinic keratoses recurred in 53.9% of patients who had had face and scalp lesions and 56% of patients with trunk and extremity lesions.
The most common adverse reactions were pain, pruritus, irritation, and infection at the application site. Skin reactions included erythema, flaking, crusting, swelling, pustulation and ulceration which were generally transient. Eye problems (eyelid and periorbital oedema) were more common with ingenol mebutate than with placebo. Patients are advised to avoid the eye area and wash their hands after applying the gel.
Three treatment-related serious adverse events have been reported – one case of Bowen's disease (mild) and two cases of squamous cell carcinoma (mild and moderate).
Ingenol should not be applied immediately before or after having a shower or within two hours of bedtime. After the gel has been applied, touching the area should be avoided for six hours. It is important to store ingenol at 2–8° C at all times.
In conclusion, ingenol mebutate is more effective than placebo for treating actinic keratoses. However, lesions are likely to recur in over 50% of patients after a year. Although this gel has not been directly compared to other topical treatments, a Cochrane review found its short-term efficacy was similar to diclofenac, fluorouracil and imiquimod.2 The advantage of ingenol mebutate is that only 2–3 applications are needed, whereas other creams and gels must be applied for weeks or months.