Dermatology Research Centre, The University of Queensland, School of Medicine, Translational Research Institute, Brisbane, QLD, Australia.
Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Br J Dermatol. 2016 Feb;174(2):305-11. doi: 10.1111/bjd.14245. Epub 2016 Jan 9.
LEO 43204 is a novel ingenol derivative in development for the treatment of actinic keratosis.
To compare the safety and preliminary efficacy of three doses of LEO 43204 with ingenol mebutate in actinic keratoses (AKs).
Patients with at least three visible, discrete, nonkeratotic AKs on four separate selected treatment areas on the forearms received LEO 43204 gel (0·025%, 0·05% and 0·075%) and ingenol mebutate 0·05% gel, by investigator-blinded, randomized allocation, for 2 consecutive days. Patients were assessed at 8 weeks. Primary outcomes included maximum composite local skin response (LSR) score and adverse events (AEs). Secondary outcomes included a reduction in the number of visible AKs.
Forty patients completed the trial. For all treatments, mean LSR scores peaked at week 1, and were below baseline by week 8. Mean maximum composite LSR scores for LEO 43204 0·025%, 0·05% and 0·075% were 9·2 (Dunnett adjusted P = 0·02), 10·1 (Dunnett adjusted P = 0·90) and 11·2 (Dunnett adjusted P < 0·01), respectively, vs. ingenol mebutate 0·05% gel (10·0). The most frequent AEs across all treatments were application site pruritus, burning sensation and tenderness. Mean reduction in the number of AKs was comparable for ingenol mebutate and the two lowest doses of LEO 43204 (71·9-73·1%), but LEO 43204 0·075% gave a significantly larger reduction (81·8%; Dunnett adjusted P = 0·04).
LEO 43204 had a similar safety profile to ingenol mebutate and a dose-response relationship for LSRs was demonstrated. The highest LEO 43204 dose (0·075%) significantly reduced the AK count when compared with ingenol mebutate.
LEO 43204 是一种新型的 ingenol 衍生物，正在开发用于治疗光化性角化病。
比较三种剂量的 LEO 43204 与 ingenol 美泊他昔在光化性角化病（AK）中的安全性和初步疗效。
至少有三个可见的、离散的、非角化 AK 的患者在前臂的四个不同的选定治疗区域接受 LEO 43204 凝胶（0.025%、0.05%和 0.075%）和 ingenol 美泊他昔 0.05%凝胶，通过研究者盲法、随机分配，连续两天给药。患者在 8 周时进行评估。主要结局包括最大复合局部皮肤反应（LSR）评分和不良事件（AE）。次要结局包括可见 AK 数量的减少。
40 名患者完成了试验。对于所有治疗方法，平均 LSR 评分在第 1 周达到峰值，第 8 周时低于基线。LEO 43204 0.025%、0.05%和 0.075%的平均最大复合 LSR 评分分别为 9.2（Dunnett 调整 P = 0.02）、10.1（Dunnett 调整 P = 0.90）和 11.2（Dunnett 调整 P < 0.01），分别与 ingenol 美泊他昔 0.05%凝胶（10.0）相比。所有治疗方法中最常见的 AE 是用药部位瘙痒、烧灼感和触痛。与 ingenol 美泊他昔和两种最低剂量的 LEO 43204（71.9-73.1%）相比，AK 数量的平均减少相当，但 LEO 43204 0.075%的减少幅度明显更大（81.8%；Dunnett 调整 P = 0.04）。
LEO 43204 的安全性与 ingenol 美泊他昔相似，并证明了 LSR 存在剂量反应关系。与 ingenol 美泊他昔相比，最高剂量的 LEO 43204（0.075%）显著减少了 AK 计数。
