近日，西班牙庞培法布拉大学Ana Maria Giménez-Arnau团队研究了局部使用Delgocitinib乳膏与口服阿利维甲酸治疗成人严重慢性手部湿疹的疗效和安全性。该项研究成果发表在2025年4月16日出版的《柳叶刀》杂志上。

慢性手部湿疹是一种影响手部和手腕的异质性、波动性和持久性疾病，严重影响生活质量。对于严重的慢性手湿疹，局部皮质类固醇往往不能令人满意，需要全身治疗。这项头对头的iii期DELTA FORCE试验的目的是评估外用delgocitinib乳膏与口服阿利维甲酸的疗效和安全性，阿利维甲酸是目前唯一被批准用于治疗严重慢性手部湿疹的全身药物。

这项随机、评估人员盲的试验在奥地利、加拿大、法国、德国、意大利、挪威、波兰、斯洛伐克、西班牙和英国的102个试验中心进行。患有严重慢性手部湿疹的成人（年龄≥18岁）通过互动反应技术系统随机（1:1）分配到delgocitinib乳膏20 mg/g（每日2次）或阿利维甲酸30 mg（每日1次），持续24周。主要终点是手部湿疹严重程度指数（HECSI）评分从基线到第12周的变化。delgocitinib乳膏与阿利维甲酸的疗效在所有符合条件的随机分配的患者中进行评估，这些患者在基线时有可用的数据，并且在所有接受试验治疗的患者中评估安全性。

2022年6月15日至2023年12月5日，513名患者（其中334名[65%]女性和179名[35%]男性）被随机分配接受delgocitinib乳膏（n=254）或阿利维甲酸（n=259）。10例患者在随机化后因不符合资格标准而被排除，因此完整的分析集包括delgocitinib组的250例患者和阿利维甲酸组的253例患者。delgocitinib组的1名患者和阿利维甲酸组的3名患者被排除在初步分析之外，因为他们在基线时缺少HECSI数据。delgocitinib乳膏从基线到第12周，HECSI评分的最小二乘平均变化显著增加（-67·6 [SE 3.4]；N =249）vs阿利维甲酸（-51·5[3·4]；n = 250;差异- 16.1,p< 0.0001）。delgocitinib组报告不良事件的患者（253例患者中125例[49%]）少于阿利维甲酸组（247例患者中188例[76%]）。最常见的不良事件是头痛（delgocitinib组为10例[4%]，阿利维甲酸组为80例[32%]）、鼻咽炎（30例[12%]对34例[14%]）和恶心（1例[<；1%]对14例[6%]）。

研究结果表明，与口服阿利维甲酸相比，Delgocitinib乳膏在24周内显示出更好的疗效和更有利的安全性。这些结果支持delgocitinib乳膏对严重慢性手湿疹患者的益处。

附：英文原文

Title: Efficacy and safety of topical delgocitinib cream versus oral alitretinoin capsules in adults with severe chronic hand eczema (DELTA FORCE): a 24-week, randomised, head-to-head, phase 3 trial

Author: Ana Maria Giménez-Arnau, Andreas Pinter, Wiebke Sondermann, Ziad Reguiai, Richard Woolf, Charles Lynde, Franz J Legat, Antonio Costanzo, Juan F Silvestre, Natja Mellerup, Marie Louise sterdal, Ursula Plohberger, Lasse Ryttig, Andrea Bauer

Issue&Volume: 2025-04-16

Abstract:

Background

Chronic hand eczema is a heterogeneous, fluctuating, and long-lasting disease affecting the hands and wrists that substantially affects quality of life. For severe chronic hand eczema, topical corticosteroids are often unsatisfactory and systemic treatment can be required. The aim of the head-to-head, phase 3 DELTA FORCE trial was to evaluate the efficacy and safety of topical delgocitinib cream versus oral alitretinoin, the only currently approved systemic drug for severe chronic hand eczema.

Methods

This randomised, assessor-masked, trial was conducted at 102 trial centres in Austria, Canada, France, Germany, Italy, Norway, Poland, Slovakia, Spain, and the UK. Adults (aged ≥18 years) with severe chronic hand eczema were randomly assigned (1:1) via an interactive response technology system to delgocitinib cream 20 mg/g (twice daily) or alitretinoin 30 mg (once daily) for up to 24 weeks. The primary endpoint was change in Hand Eczema Severity Index (HECSI) score from baseline to week 12. Efficacy of delgocitinib cream versus alitretinoin was assessed in all eligible randomly assigned patients who had available data at baseline, and safety was assessed in all patients exposed to trial treatment. The trial is registered with ClinicalTrials.gov (NCT05259722) and is complete.

Findings

Between June 15, 2022, and Dec 5, 2023, 513 (334 [65%] female and 179 [35%] male) patients were randomly assigned to receive delgocitinib cream (n=254) or alitretinoin (n=259). Ten patients were excluded after randomisation due to not meeting eligibility criteria, so the full analysis set consisted of 250 patients in the delgocitinib group and 253 in the alitretinoin group. One patient in the delgocitinib group and three in the alitretinoin group were excluded from the primary analysis as they had missing HECSI data at baseline. A significantly greater least squares mean change in HECSI score from baseline to week 12 was observed with delgocitinib cream (–67·6 [SE 3·4]; n=249) versus alitretinoin (–51·5 [3·4]; n=250; difference –16·1 [95% CI –23·3 to –8·9], p<0·0001). Fewer patients reported adverse events in the delgocitinib group (125 [49%] of 253 patients) than in the alitretinoin group (188 [76%] of 247). The most frequent adverse events were headache (ten [4%] in the delgocitinib group vs 80 [32%] in the alitretinoin group), nasopharyngitis (30 [12%] vs 34 [14%]), and nausea (one [<1%] vs 14 [6%]).

Interpretation

Delgocitinib cream showed superior efficacy and a more favourable safety profile versus oral alitretinoin over 24 weeks. These results support the benefit of delgocitinib cream in patients with severe chronic hand eczema.

DOI: 10.1016/S0140-6736(25)00001-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00001-7/abstract