Long-term follow-up study of ingenol mebutate gel for the treatment of actinic keratoses.

IMPORTANCE Ingenol mebutate is the active agent (a macrocyclic diterpene ester) in the sap of the plant Euphorbia peplus. This herb has been used as a traditional remedy for several different skin lesions, including skin cancers. OBJECTIVE To assess 12-month recurrence rates and safety associated with ingenol mebutate gel treatment in patients who previously had achieved complete clearance of actinic keratoses. DESIGN AND SETTING The treatment area was observed for recurrence for 12 months after the original study. Patients were treated in an outpatient setting. PARTICIPANTS Patients received ingenol mebutate gel, 0.015%, daily for 3 consecutive days for actinic keratoses on the face or scalp or ingenol mebutate gel, 0.05%, daily for 2 consecutive days for actinic keratoses on the trunk or extremities. Study participants had achieved complete clearance in a prespecified 25-cm2 area at day 57 of their original trial. MAIN OUTCOME MEASURES Recurrence rates and safety were assessed. RESULTS In total, 108 patients with complete clearance of face or scalp lesions in the original trial and 76 patients with complete clearance of trunk or extremity lesions in the original trial were enrolled in the 12-month observational follow-up study. Of these, 100 patients (face or scalp) and 71 patients (trunk or extremities) completed all 12 months. The sustained lesion reduction rates compared with baseline were 87.2% for the face or scalp and 86.8% for the trunk or extremities. The estimated median times to recurrence were 365 days (face or scalp) and 274 days (trunk or extremities). There were no safety concerns during the follow-up period. CONCLUSION AND RELEVANCE Ingenol mebutate gel applied as field therapy for 2 or 3 consecutive days to treat actinic keratoses produced clinically relevant sustained clearance and long-term lesion reduction. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT00953732, NCT00952783, and NCT00989313.