Evaluation of the tolerability and safety of a 0.015% ingenol mebutate gel compared to 5% 5-fluorouracil cream for the treatment of facial actinic keratosis: a prospective randomized trial

Abstract

BackgroundFive per cent 5-fluorouracil (5-FU) cream is a well-established treatment for actinic keratosis (AK), and ingenol mebutate gel (IMB) is a novel topical field-directed therapy. ObjectiveTo compare the tolerability and safety of IMB with that of 5-FU for the treatment of facial AK. MethodsAn open-label, prospective, randomized, controlled clinical trial with 100 patients with AKs within a 25-cm(2) contiguous field on the face was conducted. IMB was applied daily for three consecutive days. 5-FU was applied twice a day for 4weeks. The treatment effect and the adverse events were evaluated at baseline and on days 2, 3, 4, 8, 15, 22, 29, 36 and 43 for intent-to-treat populations. ResultsThe mean (SD) maximum local skin reactions (LSR) for patients treated with IMB was 10.85 (+/- 3.12), compared with 10.86 (+/- 3.55) for those who received 5-FU. Patients in the IMB group presented LSR that peaked at day 4 and almost completely regressed after 15days. Differently, in the 5-FU group, the LSR peaked at day 29 and lasted until visit 36. Additionally, the area under the curve (LSRxvisit) was significantly smaller for IMB. No differences between the treatments for pruritus, pain, tearing, conjunctival hyperaemia or headaches were noted, but the eyelid oedema rate was higher for IMB group. No significant difference in the proportion of dropouts was observed between groups. Both treatments demonstrated a suitable safety profile. ConclusionFor treating AKs, the local skin reactions in the IMB group were more short-lived compared with those of 5-FU, but both treatments seemed to be safe and tolerable.