Alitretinoin

▎药明康德内容团队编辑 手部红斑、丘疹、水疱、糜烂、渗出等，伴或不伴有瘙痒等症状的手部湿疹皮炎样改变，临床称为手部湿疹或手部皮炎，终生患病率约为15%。多达2/3的手部湿疹会演变为慢性病，即持续3个月以上或在12个月内复发2次及以上。 近期，《柳叶刀》（The Lancet）发表一项关于手部湿疹的综述，阐述了手部湿疹的主要影响因素、临床症状和诊断以及当前相关治疗措施的进展，以期为临床管理慢性手部湿疹提供参考。 截图来源：The Lancet 特应性皮炎和皮肤干燥是导致手部湿疹的主要影响因素 手部湿疹常见于成人，平均发病年龄在20岁左右。特应性皮炎和皮肤干燥是导致手部湿疹的主要影响因素。特应性皮炎、暴露于刺激物（如摩擦）和接触过敏原（如某些香料、橡胶添加剂等）是导致手部湿疹的主要外在因素，而有些职业可能需要长期接触某些刺激物（如理发师、美容师等），也会增加手部湿疹的发生风险。 ▲手部湿疹通常由内源性因素和刺激性或接触过敏原等因素共同导致（图片来源：参考文献[1]） 手部湿疹的症状和临床诊断 手部湿疹通常表现为手掌发红、水肿和浸润、水疱、糜烂、鳞屑、角化过度和裂纹。手部湿疹急性期以渗出、水疱和结痂为主，而慢性期以浸润和鳞屑为主，主要症状为皮肤瘙痒和疼痛。值得注意的是，高达30%的慢性手部湿疹患者同时存在足部湿疹。如下图所示，图A为角化过度-裂隙型手部湿疹，表现为红斑斑块伴鳞屑，可覆盖整个手掌，有裂隙或皲裂；图B为复发水疱型手部湿疹，表现为手掌、手指掌侧和外侧出现瘙痒、复发性、对称性、深层、1~2 mm的充满液体的水疱，水疱迅速破裂，数周后消退。水疱周围通常很少或没有红斑。 ▲手部湿疹的不同表现（图片来源：参考文献[1]） 手部湿疹的诊断需考虑到病史、临床特征，同时排除其他诊断。询问患者病史时应详细了解发病时间、病程（发作-复发性或持续性）、有无潜在刺激物及特应性皮炎病史等。慢性手部湿疹，特别是疑似有接触性过敏时，可采用斑贴试验。若斑贴试验结果为阳性，表明患者接触了致敏性物质，需结合患者病史、暴露情况和临床病程来评估。皮肤点刺、抓挠试验或测量过敏原特异性IgE浓度对诊断手部湿疹通常价值不大，但在某些特殊情况可能是有用的，如疑似患者患有罕见接触性荨麻疹综合征，对植物或动物来源的乳胶或蛋白质过敏，在持续或重复暴露的情况，可能会引起手部湿疹。几种皮肤病症状表现类似手部湿疹，临床需注意加以鉴别，如银屑病、手掌角化病、掌跎脓疱病、皮肤癣菌感染等。 目前已有各种工具可用于测量手部湿疹严重程度，但由于多数评估工具并未得到有效验证，因此临床实际使用的频率并不高，相对常用的临床评估工具有：手部湿疹严重程度指数（HECSI）、皮肤病生活质量指数。 手部湿疹的治疗和管理 慢性手部湿疹的管理核心在于做好患者教育，识别和避免接触外源性触发饮食，改善症状，实现长期疾病控制。临床可选择的治疗方式较多，如使用润肤剂持续修复表皮屏障、外用糖皮质激素、钙调磷酸酶抑制剂等治疗，以及额外的光疗或全身治疗等。 外用治疗 尽管相关支持性证据较少，但适当使用润肤剂（保湿剂）是慢性手部湿疹管理的重要组成部分。润肤剂有助于保持和补充皮肤表皮水分，减少瘙痒，延长疾病发作间隔。对于急性和渗出性手部湿疹，可首选具有抗菌作用的亲水性乳膏或凝胶，而慢性手部湿疹可能更适合选择油包水型软膏剂。 外用糖皮质激素是慢性手部湿疹的主要替代疗法，短期使用证据等级较低，而中长期使用证据等级为中等。短期内急性干预治疗，可使用传统外用糖皮质激素，如丙酸氯倍他索或曲安奈德。如果需长期使用，为了减少可能出现的不良反应，如表皮屏障修复受损，可考虑使用治疗指数更高的外用糖皮质激素，如糠酸莫米松乳膏。 钙调磷酸酶抑制剂是非甾体抗炎药，有软膏（0.03%和0.1%的他克莫司软膏适用于成人，0.03%适用于年龄≥2岁的儿童）和乳膏（1%的吡美莫司乳膏适用于年龄≥2岁的患者）两种类型，被批准用于治疗特应性皮炎，但不用于治疗其他原因引起的手部湿疹。尽管目前只有少部分短期试验证据支持使用0.1%的他克莫司软膏，但其仍被推荐用于外用糖皮质激素难治性或需要长期治疗的手部湿疹患者的二线短期治疗，因为从现有证据来看用药具备安全性，不会干扰表皮屏障修复。尚无令人信服的证据表明，吡美莫司乳膏适用于治疗手部湿疹。病情缓解后，通常以每周2~3次的频率，使用外用糖皮质激素或钙调磷酸酶抑制剂作为二级预防策略应该是可行的。 Delgocitinib属于外用泛JAK抑制剂，已被日本监管局批准用于治疗特应性皮炎。鉴于其在两项随机双盲对照试验中展现出的良好疗效和安全性，最近被欧盟委员会（EC）推荐用于治疗无法使用外用糖皮质激素或外用糖皮质治疗效果不佳的成人严重慢性手部湿疹。Delgocitinib的批准主要是基于包括DELTA 1和DELTA 2临床3期试验的结果，这些试验评估了delgocitinib相较于安慰剂的安全性和疗效。两项试验均达到了其主要和所有次要终点，详细试验结果发布于今年7月的《柳叶刀》。 两项试验的主要终点是第16周时研究者整体评估的慢性手部湿疹治疗成功（IGA-CHE TS）。治疗成功定义为IGA-CHE评分为0（皮损清除）或1（皮损几乎清除），且较基线至少提高两级。试验数据显示，在第16周时，delgocitinib治疗组比对照组有更高比例的患者达到IGA-CHE治疗成功的标准。DELTA 1中delgocitinib治疗组患者达到治疗成功标准的患者比例为20%，对照组为10%。在DELTA 2中delgocitinib治疗组达标的患者比例为29%，对照组为7%（两项试验均P≤0.0055）。报告不良事件的患者比例在delgocitinib治疗组和对照组中相似，发生率至少为2%的最常见不良事件（如鼻咽炎）在两组中相似。 光疗 如果外用措施无法控制病情，则可考虑短期光疗（通常为4~8周），但需要考虑到光疗相对周期较长，且长期应用可能存在不良反应，如皮肤癌风险（非黑色素瘤）。 系统治疗 若外用治疗和支持性措施均无法充分控制疾病时，可能需要系统治疗。阿利维A酸是首个在欧洲获准用于治疗手部湿疹的口服药物，鉴于其高质量的临床试验证据和真实世界证据，最近的欧洲指南将其作为一线系统性治疗选择。常规治疗周期长达24周，若用药后症状有所改善但未完全“治愈”，可考虑延长用药时长。对于用药效果良好，但停药后复发的患者，重新开启治疗可能是有效的。需要注意的是，阿利维A酸具有致畸性，在治疗前、治疗期间和治疗后1个月内均需做好避孕措施。用药后可能出现的不良反应是短暂性头痛、胆固醇、甘油三酯、转氨酶升高和甲状腺功能水平降低，因此需要定期抽血检查相关指标。 目前尚未有系统性糖皮质激素用于治疗慢性手部湿疹治疗的临床试验证据，根据相关指南建议，仅在严重手部湿疹急性干预时可考虑短期使用，通常为0.5~1.0 mg/kg/d泼尼松龙，而后2~3周逐步减量。 此外，部分系统性治疗被批准用于治疗中重度特应性皮炎，如短期和长期使用的全身性JAK抑制剂abrocitinib、baricitinib和upadacitinib，以及长期应用的生物制剂，如dupilumab、tralokinumab和lebrikizumab，可能是特应性皮炎伴手部湿疹或重度特应性手部湿疹患者的全身性治疗替代选择。一些小规模的观察性研究和相关特应性皮炎研究的事后分析显示，应用dupilumab、upadacitinib和abrocitinib具有一定的有效性。目前正在开展相关临床试验中。 辅助治疗 健康教育有助于加强人们自我管理意识，这是慢性病护理的重要组成部分。一般初级预防指提高人们意识和做出行为改变，以及对于高风险人群（如特应性皮炎患者）采取相关保护皮肤措施。二级预防可包含：面对面教育和实践研讨会、提供个人防护措施（如防护手套、避免接触过敏原和刺激物、手部清洁、使用润肤剂等）。对于严重和顽固性手部湿疹，采取三级预防措施是必要的，如在门诊或住院时选择专科治疗中心。 仍有待解决的问题 由于不同手部湿疹患者的症状、病程和治疗反应存在较大差异，因此在疾病分类上尚缺乏普遍可接受的分类标准，也因此影响了后续的诊断、疾病活动评估和选择合理治疗方案。类似地，尽管有较多的慢性手部湿疹的评估工具，但不同评估工具之间也存在较大差异，未来需要整合现有证据，将不同类型手部湿疹划分到合理的亚型分类中，开发基于指南共识核心而衍生的合理评估工具，制定针对预防和治疗措施的标准化评价标准，这也有利于未来开展更多临床试验，解决慢性手部湿疹患者未竟需求。 小结 手部湿疹是一种非常普遍的皮肤病，多达2/3的患者可能发展为慢性病，严重影响个人正常生活。慢性手部湿疹的临床症状随着时间的推移，在严重程度和皮肤外观表现上会有所不同。影响其发病的因素也较多，主要是当前或既往患有特应性皮炎，或是长期暴露于过敏原。治疗策略包括患者教育、避免接触过敏原、采取一级至三级预防措施，合理使用外用糖皮质激素、钙调磷酸酶抑制剂或泛JAK抑制剂等，必要时可考虑光疗、阿利维A酸全身治疗等措施。未来仍需开展更多研究，以了解慢性手部湿疹的亚型和潜在发病机制，以及比较不同治疗的有效性和安全性。 点击文末“阅读原文/Read more”，即可访问The Lancet官网阅读完整论文。 推荐阅读 欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。 参考资料（可上下滑动查看） [1] Weidinger S, Novak N. Hand eczema. Lancet. 2024 Dec 14;404(10470):2476-2486. doi: 10.1016/S0140-6736(24)01810-5. Epub 2024 Nov 29. PMID: 39615508. [2] European Commission Approves LEO Pharma’s Anzupgo® (delgocitinib) Cream for Adults with Moderate to Severe Chronic Hand Eczema (CHE). Retrieved September 23, 2024 from https://www.businesswire.com/news/home/20240923751725/en [3] LEO Pharma Announces Positive Phase 3 Head-to-head Data Results from DELTA FORCE Trial Comparing Delgocitinib Cream With Alitretinoin Capsules in Adults With Severe Chronic Hand Eczema (CHE). Retrieved January 24, 2024 from https://www.businesswire.com/news/home/20240123989016/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。 如有其他合作需求，请联系wuxi_media@wuxiapptec.com 分享，点赞，在看，传递医学新知

BALLERUP, Denmark--( BUSINESS WIRE )-- NOT FOR UK USE – NOT INTENDED FOR UK MEDIA LEO Pharma A/S, a global leader in medical dermatology, today presented late-breaking data on the DELTA FORCE trial and shared six additional abstracts as part of the scientific program for Anzupgo ® (delgocitinib) cream as a potential treatment for adult patients with moderate to severe chronic hand eczema (CHE), for whom topical corticosteroids are inadequate or inappropriate. The findings for delgocitinib cream have been delivered as part of one of LEO Pharma’s most extensive scientific programs to date at the 33 rd European Academy of Dermatology and Venereology (EADV) Congress in Amsterdam. 1-7 The 12-week head-to-head DELTA FORCE phase 3 clinical trial (N=513) evaluated the efficacy and safety of delgocitinib cream compared with oral alitretinoin capsules. 8 Alongside delgocitinib cream, alitretinoin is the only other treatment currently approved in the European Union to specifically treat severe CHE in patients who do not respond to topical corticosteroids. 9-11 Delgocitinib cream achieved the primary outcome measure of the trial, with a significantly greater least squares (LS) mean decrease in Hand Eczema Severity Index (HECSI) score from baseline to Week 12 (67.6) compared to alitretinoin (51.5, P<0.001). 1 The topical treatment also demonstrated superiority to alitretinoin across all key secondary outcome measures. This included a significantly greater proportion of delgocitinib cream patients achieving Investigator’s Global Assessment (IGA)-CHE treatment success (TS) after 12 weeks (27.2%) compared to those receiving alitretinoin (16.6%; P=0.004). Patients who received delgocitinib cream also experienced fewer treatment-emergent adverse events (AEs) (49.4%) compared to those receiving alitretinoin capsules (76.1%). 1 “ The completion of the DELTA FORCE study marks a significant milestone in our understanding of moderate to severe chronic hand eczema treatment,” said Kreesten Meldgaard Madsen, Chief Development Officer, LEO Pharma. “ With the full results now available, we have gained a new understanding of how topical treatment with delgocitinib cream compares to alitretinoin. This groundbreaking news forms just one part of the vast amount of data LEO Pharma is presenting at EADV 2024, all of which work to address the critical unmet needs of dermatology patients.” “ Alongside the results of DELTA FORCE, an extensive body of work, encompassing clinical trial data, real-world findings from both clinicians and patients, and a detailed biopsy analysis provides a multifaceted view of CHE and its treatment landscape,” said Alexander Egeberg, Head of Global Medical Affairs, LEO Pharma. “ T his data not only enhances our knowledge of CHE management but also potentially paves the way for a new topical option in clinicians’ therapeutic arsenal.” Additional novel investigational delgocitinib cream research: A post hoc analysis of 638 patients treated with delgocitinib cream across the DELTA 1, 2, and 3 clinical trials investigated the drug’s efficacy across 5 subtypes of CHE after 16 weeks of treatment. The following 5 CHE subtypes were built into the analysis: irritant contact dermatitis, vesicular hand eczema, allergic contact dermatitis, atopic hand eczema and hyperkeratotic hand eczema. 2 Data from the large multi-national RWEAL study (N=1939) found that CHE patients often present with signs, symptoms and multiple aetiological subtypes. 3 This was presented at EADV alongside other RWEAL data that showed a significant proportion of patients had no other dermatological or atopic condition besides CHE, with fewer than half (43.8%) ever having atopic dermatitis. 4 Together, these data show that CHE is a distinct, complex condition with a significant unmet need. 3,4 Real-world findings from the population-based CHECK study found that the health-related quality of life of CHE patients is increasingly impaired at each step of the treatment ladder, with a mean Dermatology Life Quality Index (DLQI) score of 5.9 for participants reporting treatment with injectables, 6.6 for topical corticosteroids, and 3.0 for those not currently on treatment. 5 Qualitative analysis of DELTA 1 patient exit interviews (N=27) confirms the sizable real-world impact of CHE disease burden. An impact on daily living was reported by 96.3% of patients and 88.9% reported an impact on emotional wellbeing due to their CHE. 6 Another presentation examined the biopsy samples analysis of 41 patients and showed severe CHE was associated with a strong dysregulation of genes in various pathways involved in skin inflammation and barrier function. Treatment with delgocitinib cream appeared to normalize the inflammatory processes and restore skin barrier integrity by inhibiting JAK signalling pathways. 7 In addition to the data submitted, LEO Pharma will also present a symposium on Friday the 27 th of September, titled “ Chronic Hand Eczema Breaking the Silent Conversation”. The session will explore the role of patient voices when managing CHE. *ENDS* About the DELTA FORCE Trial DELTA FORCE was a 24-week, randomized, assessor-blinded, active-controlled, parallel-group, phase 3, two-arm trial to compare the efficacy and safety of delgocitinib cream twice-daily with oral alitretinoin capsules once-daily in adult participants with severe chronic hand eczema. 8 The primary endpoint of the trial was the change in Hand Eczema Severity Index (HECSI) score from baseline to Week 12. Participants assigned to receive delgocitinib cream applied the drug to the skin twice a day for 16 weeks. Participants assigned to receive alitretinoin capsules took the drug orally once a day for 12 weeks. All participants were permitted to continue for up to 24 weeks if the doctor considered that they were benefiting from the treatment. 8 About the DELTA 1, 2 and 3 Trials The primary objective for the randomized, double-blind, vehicle-controlled, multi-center phase 3 clinical trials (DELTA 1 and DELTA 2) was to evaluate the efficacy of twice-daily applications of delgocitinib cream compared with cream vehicle in the treatment of adults with moderate to severe CHE. 12-14 The primary endpoint of the trials was the Investigator’s Global Assessment for chronic hand eczema treatment success (IGA-CHE TS) at Week 16. Treatment success was defined as an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a two-step improvement from baseline. Additional IGA-CHE scores included 2 (mild), 3 (moderate), and 4 (severe). 12-14 Key secondary endpoints at Week 16 included reduction of itch and pain scores of ≥4 points measured by the Hand Eczema Symptom Diary (HESD) from baseline to Week 16, as well as at least 75% improvement from baseline and at least 90% improvement from baseline on the Hand Eczema Severity Index (HECSI) at Week 16. The number of treatment-emergent adverse events from baseline to Week 16 defined the key safety endpoint of the trials. 12-14 Subjects who completed 16 weeks of treatment with delgocitinib cream or cream vehicle twice daily in trials DELTA 1 or DELTA 2 were offered to roll-over to the 36-week DELTA 3 Open-label, Multi-site Extension trial. The purpose of this extension trial was to evaluate the long-term safety of delgocitinib. 15 About the RWEAL study The RWEAL (Real-World trEatment & mAnagement of chronic hand eczema in cLinical practice) study is a medical chart review which involved (n=292) physicians from Canada, Germany, France, Italy, Spain, and the UK. Patients ≥18 years of age with moderate to severe CHE treated with TCS in the past 12 months, or with TCS contraindication, were randomly selected from physician’s overall caseload in the preceding 12 months. Data on treatments used in the 12 months prior to the last visit was collected and analyzed descriptively. 3,4 The objective of the RWEAL study was to investigate treatment patterns in patients with moderate to severe CHE over 12 months, focusing on topical corticosteroid (TCS) therapy. 3,4 About the CHECK study CHECK (Chronic Hand Eczema epidemiology, Care, and Knowledge of real-life burden) is a population-based study which recruited (n=60,131) participants in six countries including Canada, Germany, France, Italy, Spain, and the UK aged 18-69 via online panels. Participants were representative of the general population regarding sex, age, region, employment status, urban/rural setting, and, for the UK, ethnicity. 5,16 The objective of the CHECK study was to investigate and analyze self-reported disease severity, symptoms, and treatments in CHE. Furthermore, the study estimated the prevalence of CHE among adults aged 18 to 69 in the general population and described the prevalence according to key socio-demographic characteristics. The association and impact of CHE on exposures and occupation or household/leisure activities were also investigated. 5,16 About Chronic Hand Eczema Chronic hand eczema (CHE) is defined as hand eczema (HE) that lasts for more than three months or relapses twice or more within a year. 9,17 CHE is one the most common skin disorder of the hands with a prevalence rate of approximately 4.7%. 16 In a substantial number of patients, HE can develop into a chronic condition. 18 CHE is a fluctuating disorder characterized by itch and pain, and patients may experience signs such as erythema, scaling, lichenification, hyperkeratosis, vesicles, edema, and fissures on hands and wrists. 10 CHE has been shown to cause psychological and functional burdens that impact patient quality of life, 19 with approximately 70% of individuals who live with severe CHE admitting to problems in performing everyday activities, and suffering disruption in their daily life due to the condition. 20 Furthermore, careers and earning potential have also been shown to be impacted by the burden of living with CHE. 21 About Anzupgo ® (delgocitinib) cream Anzupgo ® (delgocitinib) cream 20 mg/g is an investigational topical pan-Janus kinase (JAK) inhibitor for moderate to severe CHE. It inhibits the activation of JAK-STAT signaling, which plays a key role in the pathogenesis of CHE. 22 The pathophysiology is characterized by skin barrier dysfunction, inflammation of the skin, and alterations of the skin microbiome. 23 Anzupgo is currently approved in the European Union for the treatment of moderate to severe chronic hand eczema (CHE) in adults for whom topical corticosteroids are inadequate or inappropriate. In 2014, LEO Pharma A/S and Japan Tobacco Inc. (JT) entered into a license agreement in which LEO Pharma gained exclusive rights to develop and commercialize delgocitinib cream for topical use in dermatological indications worldwide, excluding Japan, where JT retains rights. About LEO Pharma LEO Pharma is a global company dedicated to advancing the standard of care for the benefit of people with skin conditions, their families and society. Founded in 1908 and majority owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to advance the science of dermatology, and today, the company offers a wide range of therapies for all disease severities. LEO Pharma is headquartered in Denmark with a global team of 4,200 people, serving millions of patients across the world. In 2023, the company generated net sales of DKK 11.4 billion. References Giménez-Arnau AM, Pinter A, Sondermann W et al. DELTA FORCE trial: 24-week Phase 3 trial comparing the efficacy and safety of topical delgocitinib cream with oral alitretinoin capsules in adults with severe CHE. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Late Breaking News Session. D1T01.1. Bisonnette R, Schliemann S, Gooderham M, et al. Treatment response of delgocitinib cream according to CHE subtypes in adults with moderate to severe CHE: results from the Phase 3 DELTA 1, DELTA 2, and DELTA 3 trials. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. FC07.04. Fargnoli MN, Molin S, Bewley A, et al. The multifactorial and heterogenous nature of CHE in clinical practice: Results from the RWEAL study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P0608. Giménez-Arnau AM, Bewley A, Molin S, et al. Patient characteristics and comorbidities in moderate-to-severe CHE: Results from the RWEAL study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P2559. Bewley A, Molin S, Crepy MN, et al. Health-related quality of life in people with CHE - Findings from the multi-national CHECK study. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. E-poster Presentation. P3443. Mohandas P, Devani AR, Baranowski K, et al. Clinical trial exit interviews in patients with moderate to severe CHE: perspectives on disease burden and its impact on quality of life from participants in the phase 3 DELTA 1 trial. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. E-poster Presentation. P0532. Worm M, Jiang L, Litman T, et al. Topical pan-JAK inhibition with delgocitinib restores the molecular signature of lesional skin in patients with CHE. Presented at the European Academy of Dermatology and Venereology (EADV) Congress 2024. Amsterdam, Netherlands. 25-28 September. Oral Presentation. P0572. ClinicalTrials.gov. National Library of Medicine (U.S.). A 24 Week Trial to Compare the Efficacy and Safety of Delgocitinib Cream 20 mg/g Twice-daily With Alitretinoin Capsules Once-daily in Adult Participants With Severe Chronic Hand Eczema. Identifier: NCT05259722. https://clinicaltrials.gov/study/NCT05259722 . Diepgen TL, Andersen KE, Chosidow O, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J Dtsch Dermatol Ges. 2015;13(1):e1-e22. Thyssen JP, Schuttelaar MLA, Alfonso JH, et al. Guidelines for diagnosis, prevention, and treatment of hand eczema. Contact Dermatitis. 2022;86(5):357-378. Anzupgo ® (delgocitinib) cream. Summary of Product Characteristics. LEO Pharma; September 2024. ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 1). Identifier: NCT04871711. https://clinicaltrials.gov/study/NCT04871711 . ClinicalTrials.gov. National Library of Medicine (U.S.). Efficacy and Safety of Delgocitinib Cream in Adults With Moderate to Severe Chronic Hand Eczema (DELTA 2). Identifier: NCT04872101. https://clinicaltrials.gov/ct2/show/NCT04872101 . Bissonnette R, Warren RB, Pinter A, et al. 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. Lancet 2024; published online July 18. https://doi.org/10.1016/S0140-6736(24)01027-4 . ClinicalTrials.gov. National Library of Medicine (U.S.). Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials (DELTA3). Identifier: NCT04949841 https://clinicaltrials.gov/ct2/show/NCT04949841 . Apfelbacher C, Bewley A, Molin S, et al. Prevalence of Chronic Hand Eczema in adults: A cross-sectional multi-national study of 60,000 respondents in the general population. Presented at the 2024 European Society of Contact Dermatitis (ESCD) congress; September 04-07 2024; Dresden, Germany. Poster presentation #3 Lynde C, Guenther L, Diepgen TL, et al. Canadian hand dermatitis management guidelines. J Cutan Med Surg. 2010;14(6):267-284. Erratum in: J Cutan Med Surg. 2011 Nov-Dec;15(6):360. Bissonnette R, Diepgen TL, Elsner P, et al. Redefining treatment options in chronic hand eczema (CHE). J Eur Acad Dermatol Venereol. 2010;24 Suppl 3:1-20. Grant L, Seiding Larsen L, Burrows K, et al. Development of a Conceptual Model of Chronic Hand Eczema (CHE) Based on Qualitative Interviews with Patients and Expert Dermatologists. Adv Ther. 2020;37(2):692-706. Cortesi PA, Scalone L, Belisari A, et al. Cost and quality of life in patients with severe chronic hand eczema refractory to standard therapy with topical potent corticosteroids. Contact Dermatitis. 2014;70(3):158-168. Voorberg AN, Loman L, Schuttelaar MLA. Prevalence and Severity of Hand Eczema in the Dutch General Population: A Cross-sectional, Questionnaire Study within the Lifelines Cohort Study. Acta Derm Venereol. 2022;102:adv00626. Dubin C, Del Duca E, Guttman-Yassky E. Drugs for the Treatment of Chronic Hand Eczema: Successes and Key Challenges. Ther Clin Risk Manag. 2020;16:1319-1332. Erratum in: Ther Clin Risk Manag. 2021 Mar 18;17:233. Lee GR, Maarouf M, Hendricks AK, Lee DE, Shi VY. Current and emerging therapies for hand eczema. Dermatol Ther. 2019;32(3):e12840. MAT-76323 September 2024