Stockfleth Eggert, Jouary Thomas, Farnetani Francesca, Pascual Antonio Macaya, De Almeida Agudo Cecilia, Voisard Jean-Jacques, Bégeault Nathalie, Delarue Alain
Kath. Klinikum Bochum St. Josef-Hospital, Gudrunstraße 56, 44791, Bochum, Germany.
CH Pau, Service de Dermatologie, 4 Bd Hauterive, 64000, Pau, France.
Dermatol Ther (Heidelb). 2023 Apr;13(4):1013-1027. doi: 10.1007/s13555-023-00902-6. Epub 2023 Mar 1.
Topical 5-fluorouracil (5-FU)-containing treatments are effective for actinic keratosis (AK); however, they frequently lead to transient local skin reactions (LSRs), which often result in treatment non-adherence.
The aim of this international, phase IV clinical trial was to investigate whether addition of an emollient to topical 4% 5-FU would reduce the frequency and severity of LSRs over 4 weeks of treatment (intervention group) compared with 4% 5-FU alone (control group) in patients with AK. The primary objective was to assess the severity of LSRs (i.e. erythema, flaking/scaling, crusting, swelling, vesiculation/pustulation and erosion/ulceration) at week 4 of treatment (or before, in case of a major local reaction). Key secondary objectives were LSR total scores at weeks 2 and 8, the scores of individual LSR items at each visit, and the proportions of patients with 100% and ≥ 75% AK lesion clearance at week 8.
In total, 141 patients were included in the efficacy analysis (71 in the intervention group and 70 in the control group). There were no statistically or clinically significant differences between the treatment groups in terms of LSR total score at week 4 (overall and by subgroups defined by the number of lesions and patient age at baseline), scores of individual LSR items at any time point, and AK lesion clearance rates at week 8. LSR scores with topical 4% 5-FU alone were lower than expected. Skin reactions were the most common treatment-emergent adverse events in both groups, leading to treatment discontinuation in nine patients (12.3%) in the intervention group and seven (9.9%) in the control group. No new safety signals were observed with the addition of an emollient to 4% 5-FU.
Daily emollient applications during the 4-week treatment course did not impact the safety and efficacy profile of 4% 5-FU.
含局部5-氟尿嘧啶（5-FU）的治疗方法对光化性角化病（AK）有效；然而，它们经常导致短暂的局部皮肤反应（LSR），这常常导致治疗依从性不佳。
这项国际IV期临床试验的目的是研究在患有AK的患者中，与单独使用4% 5-FU（对照组）相比，在局部4% 5-FU中添加一种润肤剂是否会在4周的治疗期内降低LSR的频率和严重程度（干预组）。主要目标是评估治疗第4周（或在发生严重局部反应的情况下提前）时LSR的严重程度（即红斑、脱屑/鳞屑、结痂、肿胀、水疱/脓疱形成和糜烂/溃疡形成）。关键的次要目标是第2周和第8周时LSR的总分、每次访视时单个LSR项目的得分，以及第8周时AK病变清除率达到100%和≥75%的患者比例。
总共有141名患者纳入疗效分析（干预组71名，对照组70名）。在第4周时，治疗组之间在LSR总分（总体以及按病变数量和基线患者年龄定义的亚组）、任何时间点单个LSR项目的得分以及第8周时AK病变清除率方面，在统计学或临床上均无显著差异。单独使用局部4% 5-FU时的LSR得分低于预期。皮肤反应是两组中最常见的治疗中出现的不良事件，导致干预组9名患者（12.3%）和对照组7名患者（9.9%）中断治疗。在4% 5-FU中添加润肤剂未观察到新的安全信号。
在4周的治疗过程中每日使用润肤剂不会影响4% 5-FU的安全性和疗效。
