Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children

IF 11.5 1区医学 Q1 DERMATOLOGY

JAMA dermatology Pub Date : 2024-09-18 DOI:10.1001/jamadermatol.2024.3121

Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk

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引用次数: 0

Abstract

ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; P &lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; P &lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; P &lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; P &lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: NCT04773587, NCT04773600

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治疗成人和儿童特应性皮炎的 0.15% 罗氟司特乳膏

重要性可供特应性皮炎（AD）患者长期使用的安全、有效且耐受性良好的局部治疗方案有限，且依从性较低。目的评估每日一次 0.15%罗氟司特乳膏与载体乳膏在特应性皮炎患者中的疗效和安全性。两项三期随机、双盲、载药对照试验（评价罗氟司特乳膏治疗特应性皮炎的干预试验 1 和 2 [INTEGUMENT-1 和 INTEGUMENT-2]）纳入了来自美国、加拿大和波兰研究机构的患者。主要结果和测量指标主要疗效终点是第4周时特应性皮炎研究者全球评估验证成功，即得分为0或1分，且与基线相比至少改善了2个等级。次要终点包括湿疹面积和严重程度指数以及最严重瘙痒数字评分表。结果1337名患者（654名患者接受了INTEGUMENT-1治疗，683名患者接受了INTEGUMENT-2治疗）中，平均（标清）年龄为27.7（19.2）岁，761名参与者（56.9%）为女性。涉及的平均体表面积为 13.6%（标清 = 11.6%；范围为 3.0% 至 88.0%）。达到主要终点的罗氟司特患者明显多于药物治疗患者（INTEGUMENT-1：分别为 32.0% vs 15.2%；P &p;amp;lt; .001；INTEGUMENT-2：分别为 28.9% vs 12.0%；P &p;amp;lt; .001）。第4周时，在湿疹面积和严重程度指数至少减少75%方面，罗氟司特也有显著的统计学差异（INTEGUMENT-1：43.2% vs 22.0%；P&p;amp;amp;lt; .001；INTEGUMENT-2：42.0% vs 19.7%；P&p;amp;amp;lt; .001）。罗氟司特的耐受性良好，治疗中出现的不良反应较少。在每个时间点，研究人员注意到885名接受罗氟司特治疗的患者（≥95%）的用药部位没有刺激症状，885名接受罗氟司特治疗的患者（90%）的用药部位没有感觉或感觉轻微。结论和相关性在2项纳入成人和儿童的3期试验中，根据多个疗效终点，每日一次的0.15%罗氟司特乳膏相对于载体乳膏可改善AD，同时具有良好的安全性和耐受性：NCT04773587, NCT04773600

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来源期刊

JAMA dermatology DERMATOLOGY-

CiteScore

14.10

自引率

5.50%

发文量

300

期刊介绍： JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.