加拿大蒙特利尔创新研究所Robert Bissonnette团队研究了迪高替尼乳膏治疗成人慢性手部湿疹的临床疗效和安全性。2024年7月18日出版的《柳叶刀》杂志发表了这项成果。

慢性手部湿疹是一种波动性、炎症性、瘙痒性、经常疼痛的手部和手腕疾病，严重影响患者的生活质量和职业能力。3期DELTA 1和DELTA 2的目的是评估每日两次局部应用泛Janus激酶抑制剂迪高替尼乳膏20mg/g与乳膏载体对中重度慢性手部湿疹成年人的疗效和安全性。

这两项试验都是随机、双盲和载体对照的，DELTA 1在加拿大、法国、德国、意大利、波兰和英国的53个试验中心进行，DELTA 2在比利时、加拿大、丹麦、德国、荷兰、波兰和西班牙的50个试验中心进行。患有中度至重度慢性手部湿疹的成年人（年龄≥18岁）被2:1随机分配，分别接受每日两次20 mg/g的迪高替尼乳膏或乳膏载体，持续16周。主要终点是研究者在第16周对慢性手部湿疹（IGA-CHE）治疗成功的全球评估，定义为IGA-CHE评分为0（清除）或1（几乎清除，定义为仅勉强可察觉的红斑）。对所有接受试验治疗的患者进行了疗效和安全性评估。

2021年5月10日至2022年10月31日，487名患者（181名男性和306名女性）参加了DELTA 1；在2021年5月25日至2023年1月6日期间，共有473名患者（161名男性和312名女性）参加了DELTA 2。DELTA 1的325名患者和DELTA 2的314名患者被分配使用迪高替尼乳膏；DELTA 1的162名患者和DELTA 1的159名患者被分配使用乳膏载体。在第16周，与乳膏载体患者相比，接受迪高替尼治疗的患者IGA-CHE治疗成功率更高（DELTA 1组325例中有64例[20%] vs 162例中有16例[10%]，DELTA 2组313例中有91例[29%] vs 159例中有11例[7%]；两项试验p均≤0.0055）。报告不良事件的患者比例迪高替尼组（DELTA 1中325名患者中147名[45%]，DELTA 2中313名患者中143名[46%]）与乳膏载体相似（DELTA1中162名患者中82名[51%]，DELTA2中159名患者中71名[45%]]）。两个治疗组中发生在至少2%患者中的最常见不良事件相似，包括新冠肺炎和鼻咽炎。

研究结果表明，迪高替尼乳膏的疗效优于乳膏载体，并且在16周内耐受良好。这些结果支持迪高替尼乳膏作为中重度慢性手部湿疹患者的潜在治疗选择的临床益处，这些患者无法通过基本的皮肤护理实践和局部皮质类固醇充分控制自己的疾病。

附：英文原文

Title: Efficacy and safety of delgocitinib cream in adults with moderate to severe chronic hand eczema (DELTA 1 and DELTA 2): results from multicentre, randomised, controlled, double-blind, phase 3 trials

Author: Robert Bissonnette, Richard B Warren, Andreas Pinter, Tove Agner, Melinda Gooderham, Marie L A Schuttelaar, Marie-Nolle Crépy, Luca Stingeni, Esther Serra-Baldrich, Keith Baranowski, Sofie Korn, Merle Kurvits, Ursula Plohberger, Natacha Strange Vest, Sibylle Schliemann, Charles Lynde, Lyn Guenther, Maxwell Sauder, Robert Bissonnette, Jaggi Rao, Isaiah Day, Alim Devani, Andrei Metelitsa, Parbeer Grewal, Sonja Molin, Mireille Ruer-Mulard, Franoise Giordano-Labadie, Hervé Maillard, Ziad Reguiai, Claire Bernier, Camille Leleu, Julien Seneschal, Delphine Staumont-Sallé, Thomas Hubiche, Caroline Jacobzone, Abdallah Khemis, Marie-Nolle Crépy, Margitta Worm, Andrea Bauer, Sabine Sell, Swarna Ekanayake-Bohlig, Sylvia Pauser, Timo Buhl, Andreas Schwinn, Bernadette Eberlein, Sven Quist, Boris Bauer, Ketty Peris, Maria Teresa Rossi, Maria Fargnoli, Luigi Naldi, Luca Stingeni, Silvia Ferrucci, Irena Walecka-Herniczek, Dorota Krasowska, Aleksandra Lesiak, Aleksandra Okuniewska, Grayna Pulka, Malgorzata Dyczek, Bartlomiej Kwiek, Rafal Czajkowski, Hanna Myliwiec, Padma Mohandas, Sandeep Cliff, Richard Warren, Pippa Cousen, Graham Johnston, Richard Woolf, Kim Papp, David Adam, Darryl Toth, Chih-ho Hong, Irina Turchin, Firouzeh Niakosari, Elena Poulos, Jason Rivers, Jason Ohayon, Melinda Gooderham, Milan Tjioe, Thomas Rustemeyer, Marjolein S. de Bruin-Weller, Marie L.A. Schuttelaar, Judith Molhoek, Bert Oosting, Andreas Pinter, Markus Kaspari, Nina Magnolo, Michael Sebastian, Diamant Thaci, Sibylle Schliemann, Peter Radny, Nicolas Leitz, Athanasios Tsianakas, Amir Yazdi, Maria Kamstrup, Mette Sommerlund, Claus Zachariae, Witold Owczarek, Monika Dudra-Jastrzebska, Adam Reich, Elzbieta Kowalska-Oledzka, Jacek Szepietowski, Maria Poznanska, Jolanta Weglowska, Olivier Aerts, Pierre-Paul Roquet-Gravy, Sven Lanssens, Francisca Castelijns, Christelle Scheers, Erwin Suys, Bernard Kint, Esther Serra-Baldrich, José Manuel Carrascosa, Pablo de la Cueva Dobao, Rosa Izu, Juan Francisco Silvestre, Pablo Coto-Segura, Almudena Fernández-Orland

Issue&Volume: 2024-07-18

Abstract:

Background

Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema.

Methods

Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101.

Findings

Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis.

Interpretation

Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids.

DOI: 10.1016/S0140-6736(24)01027-4

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01027-4/abstract