BACKGROUND Ingenol mebutate (IngMeb) 0.015% or 0.05% is approved for actinic keratosis (AK) areas of 25 cm2 or less; some patients require treatment of larger fields. OBJECTIVE To determine efficacy and safety of IngMeb 0.027% in areas of AK of up to 250 cm2 during an 8-week initial assessment period and extended 12-month follow-up. METHODS This phase 3, randomized, double-blind, vehicle-controlled trial (NCT02361216) enrolled adult patients with 5 to 20 AK lesions on the face/scalp (25-250 cm2) or chest (approximately 250 cm2). Patients received once-daily IngMeb or vehicle for 3 consecutive days on the full face, full balding scalp, or approximately 250 cm2 on the chest. The primary endpoint was complete AK clearance (AKCLEAR 100; week 8). Additional endpoints included partial AK clearance (AKCLEAR 75), recurrence, patient satisfaction, cosmetic outcome, and safety. RESULTS IngMeb was superior to vehicle for complete AK clearance (21.4% vs 3.4%, P < .001) and AK clearance of 75% or greater (59.4% vs 8.9%, P < .001) at week 8. Probability of sustained clearance during the 12-month follow-up was 22.9% for patients treated with IngMeb. Increased treatment satisfaction and cosmetic outcomes were observed with IngMeb versus vehicle. No unexpected safety signals were identified. LIMITATIONS Localized skin responses hindered maintenance of double-blinding. CONCLUSIONS IngMeb 0.027% was superior to vehicle for treatment of AK areas of up to 250 cm2. The safety profile of IngMeb was as expected.

中文翻译：

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丁香酚丁香酚凝胶在全脸，秃头或胸部约250 cm2的光化性角化病的现场治疗中的功效和安全性：一项3期随机对照试验。

背景技术丁香酚丁二醇酯（IngMeb）的0.015％或0.05％被批准用于25 cm2或更小的光化性角化病（AK）区域；一些患者需要更大范围的治疗。目的在8周的初始评估期间和延长的12个月随访中，确定IngMeb在AK面积最大为250 cm2的区域中的疗效和安全性为0.027％。方法该3期随机，双盲，赋形剂对照试验（NCT02361216）纳入了面部/头皮（25-250 cm2）或胸部（约250 cm2）有5至20个AK病变的成年患者。患者连续3天每天接受一次IngMeb或媒介物的全脸，全秃头皮手术或胸部约250 cm2的手术。主要终点为完全AK清除（AKCLEAR 100；第8周）。其他终点包括部分AK清除（AKCLEAR 75），复发，患者满意度，美容效果和安全性。结果在第8周时，IngMeb的完全AK清除率（21.4％vs 3.4％，P <.001）和AK清除率为75％或更高（59.4％8.9％，P <.001）优于媒介物。 IngMeb治疗的患者在12个月的随访期间为22.9％。与媒介物相比，IngMeb可以提高治疗满意度和美容效果。没有发现意外的安全信号。局限性皮肤局部反应阻碍了双盲的维持。结论IngMeb 0.027％在治疗250平方厘米的AK区域方面优于媒介物。IngMeb的安全性符合预期。使用IngMeb治疗的患者，在第8周的001）中获得持续清除的可能性为22.9％。与媒介物相比，IngMeb可以提高治疗满意度和美容效果。没有发现意外的安全信号。局限性皮肤局部反应阻碍了双盲的维持。结论IngMeb 0.027％在治疗250平方厘米的AK区域方面优于媒介物。IngMeb的安全性符合预期。使用IngMeb治疗的患者，在第8周的001）中获得持续清除的可能性为22.9％。与媒介物相比，IngMeb可以提高治疗满意度和美容效果。没有发现意外的安全信号。局限性皮肤局部反应阻碍了双盲的维持。结论IngMeb 0.027％在治疗250平方厘米的AK区域方面优于媒介物。IngMeb的安全性符合预期。027％的车辆在处理250平方厘米的AK区域方面优于车辆。IngMeb的安全性符合预期。027％的车辆在处理250平方厘米的AK区域方面优于车辆。IngMeb的安全性符合预期。