• We estimate that in 2024, there were 39.2 million diagnosed prevalent cases of atopic dermatitis (AD), across all age groups, in the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). Over the forecast period (2024–43), prevalent cases are expected to decrease slightly due to changes in population trends and demographics.
  我们预估 2024 年在美国、日本及五大欧洲主要市场（法国、德国、意大利、西班牙和英国）中，各年龄段确诊的特应性皮炎（AD）流行病例数达 3920 万例。在预测期内（2024-2043 年），由于人口趋势和人口结构变化，流行病例数预计将略有下降。

• Topical agents are considered as the primary treatment for mild-to-moderate AD. Most commonly, they comprise topical corticosteroids and topical calcineurin inhibitors. Branded options also include the topical PDE4 inhibitor Eucrisa and Zoryve cream, while topical Janus kinase (JAK) inhibitor Opzelura represents a different mechanism of action.
  外用药物被视为轻中度特应性皮炎（AD）的主要治疗手段。最常见的外用制剂包括局部皮质类固醇和钙调磷酸酶抑制剂。品牌药选项还包括外用 PDE4 抑制剂 Eucrisa 和 Zoryve 乳膏，而局部 Janus 激酶（JAK）抑制剂 Opzelura 则代表了不同的作用机制。

• The success of Sanofi and Regeneron’s IL-4 receptor alpha antagonist Dupixent (dupilumab) has established the Th2 immune axis as a significant pathway in the pathogenesis of AD. As the first biologic approved in the US, Dupixent has maintained its leading position since 2017, surpassing the efficacy of the second approved biologic, Adbry (tralokinumab), which targets the IL-13 cytokine. However, this dominance is set to be challenged by Eli Lilly’s Ebglyss (lebrikizumab), an anti-IL-13 antibody approved in September 2024 that offers comparable efficacy and a more favorable safety profile alongside more convenient administration as a once-monthly injection.
  赛诺菲与再生元合作的 IL-4 受体α拮抗剂 Dupixent（度普利尤单抗）的成功，确立了 Th2 免疫轴在 AD 发病机制中的关键通路地位。作为美国首个获批的生物制剂，Dupixent 自 2017 年以来始终保持领先地位，其疗效优于第二个获批的靶向 IL-13 细胞因子的生物制剂 Adbry（曲罗芦单抗）。然而，这种主导地位将受到礼来公司 Ebglyss（lebrikizumab）的挑战——这款于 2024 年 9 月获批的抗 IL-13 抗体不仅具有相当的疗效和更优的安全性，还提供每月一次注射的便捷给药方案。

• Biologics targeting OX40 are generating some excitement due to robust and sustained responses. However, in order to gain market access, these inhibitors, including rocatinlimab, telazorlimab, and amlitelimab, will need to meet the high standards for safety and efficacy set by Dupixent. Although rocatinlimab’s Phase III ROCKET-HORIZON study met its primary endpoints, topline data did not produce satisfactory results.
  靶向 OX40 的生物制剂因其强劲且持久的疗效引发广泛关注。然而要获得市场准入，包括 rocatinlimab、telazorlimab 和 amlitelimab 在内的这些抑制剂必须达到 Dupixent 设定的高标准安全性和有效性要求。尽管 rocatinlimab 的 III 期 ROCKET-HORIZON 研究达到了主要终点，但关键数据结果仍不尽如人意。

• Galderma's anti-IL-31 receptor alpha antibody Nemluvio (nemolizumab) received another approval from the FDA in December 2024 for the treatment of atopic dermatitis, in addition to its first approval in August 2024 for treating prurigo nodularis. It is positioned in a unique niche, addressing AD by specifically targeting itch.
  高德美的抗 IL-31 受体α抗体药物 Nemluvio（nemolizumab）继 2024 年 8 月首次获批治疗结节性痒疹后，于 2024 年 12 月再获食品药品监督管理局批准用于特应性皮炎治疗。该药物通过特异性靶向瘙痒机制治疗 AD，在细分领域占据独特地位。

• Two new topical treatments are expected to impact Opzelura’s market share among mild atopic dermatitis patients, which currently carries a black box warning. The aryl hydrocarbon modulator Vtama received an approval from the FDA in December 2024, while the PDE4 inhibitor Zoryve, a 0.15% roflumilast cream for patients aged six and older, was approved in the U.S. in July 2024. In terms of numerical comparison, Vtama has shown superior treatment efficacy compared to Zoryve. However, Zoryve has a better tolerability profile, as Vtama may cause folliculitis in 10% of AD patients. Additionally, Anzupgo, a topical pan-JAK inhibitor, received EU marketing authorization in late 2024 and is pending FDA approval for treating chronic hand eczema.
  两种新型外用疗法预计将影响 Opzelura 在轻度特应性皮炎患者中的市场份额，该药物目前带有黑框警告。芳烃受体调节剂 Vtama 于 2024 年 12 月获得美国食品药品监督管理局批准，而 PDE4 抑制剂 Zoryve（一种适用于 6 岁及以上患者的 0.15%罗氟司特乳膏）则于 2024 年 7 月在美国获批。就数据对比而言，Vtama 显示出优于 Zoryve 的治疗效果。但 Zoryve 具有更好的耐受性，因为 Vtama 可能导致 10%的特应性皮炎患者出现毛囊炎。此外，外用泛 JAK 抑制剂 Anzupgo 于 2024 年底获得欧盟上市许可，目前正等待美国食品药品监督管理局批准用于治疗慢性手部湿疹。

Disease definition  疾病定义

Atopic dermatitis (AD), also known as atopic eczema, is a chronic, pruritic, relapsing inflammatory dermatological condition. The condition usually begins during early infancy and childhood, but can persist into, or start during, adulthood. AD usually fluctuates between periods of relative flares and quiescence but some individuals have chronically active disease. The exact cause of the disease is unknown; however, certain factors such as epigenetic, genetic, immunological, and environmental interactions with overlapping skin barrier defects are indicated in its pathogenesis.  An imbalance of the Th22 and Th2 cytokines which causes the disruption of keratinocytes is thought to be an important contributing factor that drives AD pathogenesis. Furthermore, impaired skin barrier function due to mutations in the epidermal barrier protein, filaggrin, could also play a crucial role in the development of AD by increasing the penetration of microbes and allergens. Although AD is not life-threatening, the disease significantly affects the quality of life of the patient and their family, which can lead to serious socioeconomic consequences.
特应性皮炎（AD），又称特应性湿疹，是一种慢性、瘙痒性、复发性炎症性皮肤病。该疾病通常在婴幼儿及儿童期发病，但可能持续至成年期或在成年期首次发作。AD 病情通常在相对急性发作期和静止期之间波动，但部分患者会长期处于疾病活动状态。该疾病的确切病因尚未明确，但表观遗传、遗传、免疫因素以及与环境因素相互作用导致皮肤屏障功能缺陷重叠，被认为是其发病机制的关键。Th22 与 Th2 细胞因子失衡导致角质形成细胞破坏，被认为是推动 AD 发病的重要诱因。此外，表皮屏障蛋白丝聚蛋白基因突变造成的皮肤屏障功能受损，可能通过增加微生物和过敏原渗透，在 AD 发展过程中起到关键作用。尽管 AD 不会危及生命，但该疾病严重影响患者及其家庭的生活质量，可能引发严重的社会经济后果。

Patient segmentation  患者分型

While 28 different scales for measuring disease severity in AD are available, none of these are recommended for use in routine clinical practice as they were primarily designed for use in clinical trials. The most commonly used disease severity scales include the SCORAD index, the Eczema Area and Severity Index (EASI), and the Investigator’s Global Assessment. Key opinion leaders interviewed by Datamonitor Healthcare confirm that disease severity measuring scales have not been adopted in clinical practice and suggest that dermatologists define disease severity by looking at the percentage of body surface area affected, the morphology of the skin lesions, and the symptoms experienced by the patient. An EASI score of 1.1–7.0 is considered as mild, 7.0–21.0 as moderate, and ≥21.1 as severe AD.
目前虽有 28 种不同的特应性皮炎疾病严重程度评估量表，但均未被推荐用于常规临床实践，因为这些量表主要针对临床试验设计。最常用的疾病严重程度评估量表包括 SCORAD 指数、湿疹面积和严重程度指数（EASI）以及研究者整体评估量表。Datamonitor Healthcare 采访的权威专家证实，临床实践中尚未采用疾病严重程度测量量表，并建议皮肤科医生通过观察受累体表面积百分比、皮损形态学特征及患者症状来判定疾病严重程度。EASI 评分 1.1-7.0 视为轻度，7.0-21.0 为中度，≥21.1 则属于重度特应性皮炎。

Symptoms  症状

Symptoms of the disease include itchy, dry skin, and red rashes which come and go. These rashes can form anywhere on the body, but the pattern may vary with age. In infants, the rashes predominantly occur on the scalp, face, hands, and feet. In childhood, the rashes are usually observed in areas such as inside the bend of the knees and elbows, and on the front part of the neck. In adolescents and adults, the rashes typically occur on the eyelids, ankles, and wrists, in addition to the creases of the knees and elbows. Furthermore, oozing or crusting of the rash and lichenification of the skin can occur due to scratching of the itchy skin. Intense pruritus can disturb sleep and affect an individual’s quality of life.
该疾病的症状包括皮肤瘙痒、干燥以及反复出现的红色皮疹。这些皮疹可出现在身体任何部位，但分布模式可能随年龄变化。婴儿期皮疹主要分布于头皮、面部、手部和足部；儿童期常见于膝窝、肘窝及颈前部；青少年和成人则多发于眼睑、脚踝、手腕等部位，同时膝肘屈侧仍会出现。此外，因搔抓可能导致皮疹渗液结痂及皮肤苔藓样变。剧烈瘙痒会影响睡眠质量，进而降低患者生活质量。

Risk factors  风险因素

A family history of atopic diseases and loss-of-function mutations in the filaggrin gene, which encodes profilaggrin, are the two major risk factors associated with disease development. Additionally, individuals with AD are more prone to other inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, and alopecia areata. Psychiatric or behavioral disorders such as depression or attention deficit hyperactivity disorders are associated with the disease, and patients with AD often also have food allergies, bronchial asthma, and allergic rhinitis. Moreover, AD also can be a result of other conditions including severe dermatitis, multiple allergies, metabolic wasting syndrome, immune dysregulation, polyendocrinopathy, enteropathy X-linked (IPEX) syndrome, and Netherton syndrome.
特应性疾病的家族史和编码聚丝蛋白的丝聚合蛋白基因功能缺失突变，是与此疾病发展相关的两大主要风险因素。此外，特应性皮炎患者更容易出现其他炎症性疾病，如类风湿性关节炎、炎症性肠病和斑秃。抑郁或注意力缺陷多动障碍等精神或行为障碍也与该疾病相关，且特应性皮炎患者常同时患有食物过敏、支气管哮喘和过敏性鼻炎。此外，特应性皮炎也可能是其他病症的结果，包括严重皮炎、多重过敏、代谢消耗综合征、免疫失调、多内分泌腺病-肠病-X 连锁（IPEX）综合征以及 Netherton 综合征。

Diagnosis  诊断

As no definitive diagnostic test exists, the diagnosis of AD is clinical and is based on historical features, the morphology and distribution of skin lesions, and related clinical signs. The dermatologist will examine the skin for any signs or symptoms and reviews the medical and family history to make a diagnosis. Sometimes, a patch test is recommended to find any allergies. Pruritus and skin lesions must be present for diagnosis, along with other supporting features such as increased IgE levels and family history of atopic disease.
由于缺乏明确的诊断性检测，特应性皮炎的诊断主要基于临床评估，需结合病史特征、皮损形态与分布情况以及相关临床体征进行综合判断。皮肤科医师会通过检查皮肤病变的体征与症状，并详细询问患者个人及家族病史来确诊。有时会建议进行斑贴试验以排查过敏原。诊断必须满足瘙痒和皮肤病变这两项核心表现，同时需具备其他支持性特征，如 IgE 水平升高和特应性疾病家族史。

Variation in clinical characteristics by age and geography
年龄与地域差异对临床特征的影响

AD is commonly referred to as a disease of childhood, as it has been cited that 85% of patients experience the onset of AD under the age of five years and outgrow the disease in late childhood; however, many of these studies have not included adults. A systematic review and meta-analysis estimated that the pooled proportion of adult-onset AD was 26.1% (16.5–37.2%), with similar results found in sensitivity analyses by diagnostic method, study region, and sex. While characteristics of child-onset and adult-onset AD are not commonly reported, the study found distinct clinical characteristics between the two, such as a higher frequency of foot dermatitis in adults.
特应性皮炎通常被视为一种儿童疾病，据称 85%的患者在 5 岁前发病并在青春期后期自愈；然而这些研究大多未纳入成人患者。一项系统综述和 Meta 分析估算，成人发病型特应性皮炎的汇总比例为 26.1%（16.5-37.2%），通过诊断方法、研究地区和性别进行的敏感性分析也得出了相似结果。虽然儿童发病型与成人发病型的特征鲜有报道，但该研究发现两者存在显著临床差异，例如成人患者足部皮炎的发生率更高。

In addition to differing clinical characteristics in children and adults, varying clinical presentations by ethnicity and underlying biologic mechanisms have been observed. Another systematic review and meta-analysis examined regional differences in AD clinical characteristics. The study found a wide range of AD signs and symptoms and phenotype differences by region. The most prevalent AD features overall were pruritus, lichenification, and xerosis. Regional differences were pronounced; for example, flexural involvement was less commonly reported in India, the Americas, and Iran, while studies from Africa reported more papular lichenoid lesions. Within Asia, which is a large geographic region comprised of many racial and ethnic groups, substantial phenotypic differences were observed.
除儿童与成人临床表现存在差异外，还观察到不同种族间的临床表现差异及潜在生物学机制差异。另一项系统综述与 Meta 分析研究了特应性皮炎临床特征的地区性差异。研究发现不同地区的特应性皮炎体征、症状及表型差异显著。总体而言，瘙痒、苔藓样变和皮肤干燥是最普遍的临床特征。地区差异尤为突出：例如印度、美洲和伊朗较少报告屈侧受累，而非洲研究则报道更多丘疹性苔藓样皮损。在包含多种族裔群体的亚洲大区域内，也观察到显著的表型差异。

Disease course influenced by emotional and/or environmental factors is another prevalent feature of patients with AD; however, this feature is not present in two major diagnostic criteria used for identifying the disease. The study highlighted the need for awareness and inclusion of regional and population-specific phenotypic differences to ensure proper diagnosis and assessment of patients with AD to contribute to more robust prevalence assessments that are more representative of the disease regionally and worldwide.
病程受情绪和/或环境因素影响是 AD 患者的另一普遍特征，然而这一特征并未体现在目前用于识别该疾病的两大主要诊断标准中。研究强调需要关注并纳入地域及人群特异性表型差异，以确保对 AD 患者进行准确诊断与评估，从而有助于建立更具代表性的区域性及全球性患病率评估体系。

The management of AD depends on the disease severity as well as associated co-morbidities. Early disease management includes moisturizers, avoiding the factors that trigger AD, and patient education. Treatment of AD mainly aims at reducing skin itching and inflammation, eliminating flare-ups, and reducing side effects. Management of the disease is very challenging as it requires several approaches including patient education, skin and epidermal barrier recovery, and controlling aggravating factors, in conjunction with several pharmacologic interventions.
AD（特应性皮炎）的管理取决于疾病严重程度及相关并发症。早期疾病管理包括使用保湿剂、避免诱发 AD 的因素以及对患者进行教育。AD 的治疗主要旨在减轻皮肤瘙痒和炎症、消除急性发作并减少副作用。由于需要采取多种方法（包括患者教育、皮肤和表皮屏障恢复、控制加重因素）并结合多种药物干预措施，该疾病的管理极具挑战性。

Non-pharmacologic interventions
非药物干预措施

Emollients play an important part in the management of AD. Patients with AD need to apply emollients several times a day, and studies have shown that regular use of emollients can reduce the need for topical corticosteroids. Emollients increase epidermal hydration by reducing water loss, as they act as an occlusive barrier on the surface of the skin. They are often included in a number of moisturizer products to help soften the skin. Moisturizers are classified into humectants and occlusive emollients, and are available in different preparations including lotions, ointments, and creams. Occlusive agents such as mineral oils, lanolin, petrolatum, olive oil, ceramide, silicone, and paraffin work by creating a thin hydrophobic film on the top of the skin to mitigate transepidermal water loss. Humectants such as alpha hydroxy acids, sorbitol, and glycerin attract the water vapor in the air to moisturize the skin. Emollients such as elastin, collagen, shea butter, and glyceryl stearate soften the skin by filling the cracks between desquamating corneocytes. Choosing an occlusive or humectant moisturizer, and the type of vehicle, depends on patient status and other factors such as cost, mechanism of action, tolerability, absence of sensitizing fragrances or agents, affected areas of the body, and degree of disease severity.
润肤剂在特应性皮炎（AD）的治疗中起着重要作用。AD 患者需要每天多次使用润肤剂，研究表明定期使用润肤剂可减少对外用糖皮质激素的需求。润肤剂通过在皮肤表面形成封闭屏障来减少水分流失，从而增加表皮水合作用。它们常被添加于多种保湿产品中以帮助软化皮肤。保湿剂分为吸湿剂和封闭性润肤剂，并有不同剂型可供选择，包括乳液、软膏和乳霜。矿物油、羊毛脂、凡士林、橄榄油、神经酰胺、硅树脂和石蜡等封闭剂通过在皮肤表层形成疏水性薄膜来减少经表皮水分流失。α-羟基酸、山梨醇和甘油等吸湿剂则通过吸附空气中的水蒸气来滋润皮肤。弹性蛋白、胶原蛋白、乳木果油和硬脂酸甘油酯等润肤剂通过填充脱屑角质细胞间的裂隙来软化皮肤。 选择封闭性或保湿性润肤剂及其载体类型，需根据患者状况及其他因素决定，如成本、作用机制、耐受性、是否含致敏香料或成分、身体受累部位以及疾病严重程度。

An emollient without perfume or any other potential allergens should be recommended, as perfumes may stimulate secondary allergic sensitization. Patients with chronic dry skin may benefit from coal tar preparations that are available in the form of occlusive bandages and creams. Furthermore, application of emollients to the skin is recommended within three minutes after a bath or shower for optimal hydration. The use of wet-wrap treatment with or without a topical corticosteroid can be recommended for individuals with moderate-to-severe AD in order to reduce disease severity and loss of water during flares. Typically, a topical agent is covered with a moist first inner layer of gauze tubular bandages, or a cotton suit, followed by a dry second outer layer. Similarly, for more generalized AD cases, two layers of non-irritating clothing can be prepared.
应推荐使用不含香料或其他潜在过敏原的润肤剂，因香料可能诱发继发性过敏反应。慢性干性皮肤患者可受益于煤焦油制剂，这类制剂有封闭性绷带和乳膏两种形式。此外，建议在沐浴后三分钟内涂抹润肤剂以达到最佳保湿效果。对于中重度特应性皮炎患者，可推荐采用湿裹疗法（无论是否联用局部皮质类固醇），以降低疾病严重程度并减少发作期水分流失。通常操作是：先以湿润的纱布管状绷带或棉质内衣作为第一层内衬覆盖局部药物，再以干燥衣物作为第二层外衬。同理，对于更广泛的特应性皮炎病例，可准备两层无刺激性的衣物进行包裹。

Medications  药物

Topical agents are considered as a primary treatment for mild-to-moderate AD. They include topical corticosteroids and topical calcineurin inhibitors.
外用药物被认为是治疗轻中度特应性皮炎（AD）的主要方法，包括外用糖皮质激素和外用钙调磷酸酶抑制剂。

Topical corticosteroids: These agents are effective in controlling AD symptoms such as skin inflammation and pruritus by reducing inflammatory mediator activity via inducing inhibitory proteins. Application of topical corticosteroids twice a day is often recommended for AD treatment; however, studies have shown that a once-daily application is just as effective. Topical corticosteroids are available in different potencies including mild, moderate, and strong. When choosing the appropriate agent, several factors such as lesion severity and the area of lesioned skin on the body should be considered to increase effectiveness and reduce side effects. Due to the risk of atrophy, very high potency steroid use is limited to short courses. However, guidelines recommend the use of medium potency topical steroids twice a week as maintenance therapy.
外用糖皮质激素：这类药物通过诱导抑制蛋白来降低炎症介质活性，从而有效控制特应性皮炎的症状，如皮肤炎症和瘙痒。通常建议每天两次使用外用糖皮质激素治疗 AD；然而，研究表明每天一次使用同样有效。外用糖皮质激素有不同的效力等级，包括弱效、中效和强效。在选择合适的药物时，应考虑皮损严重程度和身体受累皮肤面积等因素，以提高疗效并减少副作用。由于存在皮肤萎缩风险，极高效力类固醇仅限于短期使用。但指南建议每周两次使用中效外用类固醇作为维持治疗。

Topical calcineurin inhibitors: These agents are considered as an alternative therapy to topical corticosteroid treatment. Topical calcineurin inhibitors are non-steroidal immunomodulators that work to decrease the inflammation of AD by inhibiting the production of T cells and inflammatory cytokines. Protopic (tacrolimus) and Elidel (pimecrolimus) are the two topical calcineurin inhibitor treatments approved by the FDA for the treatment of mild-to-moderate AD. Protopic 0.03% ointment and Elidel 1% cream are recommended for use in individuals two years of age and older, while Protopic 0.1% ointment is indicated for only adult AD patients. Proactive therapy with intermittent use of topical calcineurin inhibitors as a maintenance treatment 2–3 times per week on areas that commonly flare is recommended for preventing relapses while minimizing the need for topical corticosteroids. This has been found to be more effective than the application of an emollient alone.
外用钙调磷酸酶抑制剂：这类药物被视为外用皮质类固醇治疗的替代疗法。外用钙调磷酸酶抑制剂是非甾体类免疫调节剂，通过抑制 T 细胞和促炎细胞因子的产生来减轻特应性皮炎的炎症反应。普特彼（他克莫司）和爱宁达（吡美莫司）是食品药品监督管理局批准用于治疗轻中度特应性皮炎的两种外用钙调磷酸酶抑制剂。推荐 2 岁及以上人群使用 0.03%普特彼软膏和 1%爱宁达乳膏，而 0.1%普特彼软膏仅适用于成年特应性皮炎患者。建议采用主动疗法，在易复发部位每周 2-3 次间歇性使用外用钙调磷酸酶抑制剂作为维持治疗，既能预防复发又可最大限度减少外用皮质类固醇的需求。临床证实该方案比单独使用润肤剂更为有效。

The American Academy of Dermatology (AAD) published updated guidelines on topical treatments for AD in 2023. The guidelines point to Protopic as more efficacious than Elidel based on data from clinical trials. However, after initial use, Protopic may cause more irritation than Elidel, and Elidel’s cream formulation may be preferred among patients. Topical calcineurin inhibitors have a black box warning of an elevated relative risk of lymphoma, although this increased risk does not extend to other cancers and, considering the low absolute risk of lymphoma, the elevated risk is not likely clinically meaningful. The guidelines also suggest that Protopic is more effective than medium potency topical steroids.
美国皮肤病学会（AAD）于 2023 年发布了特应性皮炎外用治疗的最新指南。指南指出，根据临床试验数据，普特彼（Protopic）比爱宁达（Elidel）疗效更佳。但初次使用时，普特彼可能比爱宁达更容易引起刺激反应，而爱宁达的乳膏剂型可能更受患者青睐。外用钙调磷酸酶抑制剂带有黑框警告，提示淋巴瘤相对风险升高，不过这种风险增加并不延伸至其他癌症，且考虑到淋巴瘤的绝对风险较低，这种升高的风险可能不具有临床意义。指南还表明，普特彼比中效外用类固醇药物更为有效。

Topical phosphodiesterase 4 (PDE4) inhibitors: Eucrisa (crisaborole) is a twice-daily topical treatment approved by the FDA for mild-to-moderate AD in patients aged two years and older. Due to limited efficacy, the PDE4 inhibitor is used as an alternative to topical corticosteroids and topical calcineurin inhibitors. Approved as a 2% topical ointment, Eucrisa has no specific limitations on duration of use and so may be used as a long-term maintenance therapy. While its exact mechanism of action is not clearly understood, the drug is thought to inhibit PDE4 target cells, reducing the production of pro-inflammatory cytokines that are responsible for the signs and symptoms of AD.
局部磷酸二酯酶 4（PDE4）抑制剂：Eucrisa（克立硼罗）是一种经食品药品监督管理局批准用于两岁及以上轻中度特应性皮炎患者的每日两次局部治疗药物。由于疗效有限，该 PDE4 抑制剂常作为局部皮质类固醇和局部钙调磷酸酶抑制剂的替代方案。Eucrisa 以 2%外用软膏剂型获批，在使用时长方面无特殊限制，因此可作为长期维持治疗手段。虽然其确切作用机制尚未完全阐明，但该药物被认为通过抑制 PDE4 靶细胞，减少促炎细胞因子的产生，从而改善特应性皮炎的体征与症状。

Topical Janus kinase (JAK) inhibitor: Opzelura (ruxolitinib) fills the gap for a non-steroidal treatment that may be comparable to a medium potency topical corticosteroid with minimal application site burning, which is a common complaint with Eucrisa (along with inefficacy). Placed in the second line of therapy after failure of topical steroids, initial launch has gone well, albeit heavily supported by Incyte as reimbursement challenges are worked through. The drug may provide an especially appealing option for AD patients who have facial involvement, an area where dermatologists prefer to minimize the use of steroids.
局部 Janus 激酶（JAK）抑制剂 Opzelura（鲁索替尼）填补了非甾体治疗的空白，其疗效可能相当于中效外用皮质类固醇，且用药部位灼烧感极低——而后者正是 Eucrisa（克立硼罗）常被诟病的缺点（此外还包括疗效不足）。该药物被列为外用激素治疗失败后的二线疗法，尽管面临报销挑战需依赖 Incyte 公司大力支持，但上市初期表现良好。对于伴有面部特应性皮炎的患者而言，该药物可能特别具有吸引力，因为皮肤科医生倾向于尽量减少该部位类固醇的使用。

AAD guidelines state that Opzelura 1.5% cream is approved in patients aged 12 years and older for short-term and non-continuous treatment of mild-to-moderate AD. In order to limit systemic absorption, no more than 60 grams a week should be applied, and the treatment area should not exceed 20% body surface area. Even with the topical formulation and these restrictions, the drug has a black box warning for major adverse cardiovascular events, thrombosis, serious infections, mortality, and malignancies such as lymphoma.
美国皮肤病学会（AAD）指南指出，1.5% Opzelura 乳膏获批用于 12 岁及以上患者轻度至中度特应性皮炎的短期非连续性治疗。为限制系统吸收，每周用量不应超过 60 克，治疗面积不得超过体表面积的 20%。即使采用局部制剂并遵循这些限制，该药物仍附有关于重大不良心血管事件、血栓形成、严重感染、死亡率及淋巴瘤等恶性肿瘤的黑框警告。

Systemic treatment  全身性治疗

Broad-acting immunosuppressants: Adult patients with severe AD that is difficult to manage with topical treatments alone require systemic immunosuppressive therapy. Cyclosporine, systemic corticosteroids, methotrexate, mycophenolate mofetil, and azathioprine are some of the available non-biologic systemic agents for the treatment of AD in adults. These immunosuppressive agents decrease the number of inflammatory cells, as well as the gene expression of inflammatory cytokines. Oral corticosteroids can be used for severe AD treatment, but their use should only be for the short term due to several risk factors. Medrol (methylprednisolone) and Depo-Medrol are two systemic corticosteroids approved by the FDA for the treatment of several conditions, including AD. Cyclosporine can be used as a first-line systemic treatment in moderate-to-severe AD patients who fail to show adequate response to oral antihistamines and topical therapy. Other immunosuppressive agents such as azathioprine, methotrexate, and mycophenolate mofetil have also been found to be effective in treating refractory AD.
广谱免疫抑制剂：对于仅靠局部治疗难以控制的重度特应性皮炎成人患者，需采用全身性免疫抑制疗法。环孢素、全身性皮质类固醇、甲氨蝶呤、霉酚酸酯和硫唑嘌呤是目前可用于成人特应性皮炎治疗的部分非生物制剂类全身性药物。这些免疫抑制剂能减少炎症细胞数量，并抑制炎症细胞因子的基因表达。口服皮质类固醇虽可用于重度特应性皮炎治疗，但由于存在多重风险因素，仅建议短期使用。美卓乐（甲泼尼龙）和得宝松是经美国食品药品监督管理局批准用于治疗特应性皮炎等多种疾病的全身性皮质类固醇药物。对于口服抗组胺药和局部疗法反应不佳的中重度特应性皮炎患者，环孢素可作为一线全身治疗方案。硫唑嘌呤、甲氨蝶呤和霉酚酸酯等其他免疫抑制剂也被证实对难治性特应性皮炎具有疗效。

Oral JAK inhibitors: Another mode of action for patients with moderate-to-severe AD is offered by oral JAK inhibitors. These work by inhibiting the activity of enzymes called Janus kinases, which mediate the pathways that are involved in the inflammatory process associated with AD. However, JAK inhibitors are associated with cardiovascular safety concerns. The choice to use an oral JAK inhibitor will involve proper patient selection, such as avoiding elderly patients or those with a history of thrombosis. In 2021, JAK inhibitors Rinvoq (upadacitinib) and Cibinqo (abrocitinib) gained approval to treat AD in Europe and Japan, followed by US approvals in early 2022. The AD label for Olumiant (baricitinib) was granted in Europe and Japan earlier than for Rinvoq and Cibinqo, in 2020.
口服 JAK 抑制剂：针对中重度特应性皮炎（AD）患者，口服 JAK 抑制剂提供了另一种作用机制。这类药物通过抑制名为 Janus 激酶的酶活性发挥作用，这些酶介导了与 AD 相关的炎症反应通路。但 JAK 抑制剂存在心血管安全性隐患，使用时需严格筛选患者，例如避免用于老年患者或有血栓病史者。2021 年，JAK 抑制剂 Rinvoq（乌帕替尼）和 Cibinqo（阿布昔替尼）相继在欧洲和日本获批治疗 AD，并于 2022 年初获得美国批准。而 Olumiant（巴瑞替尼）的 AD 适应症早在 2020 年就已在欧洲和日本获批，早于 Rinvoq 和 Cibinqo。

Biologics: Biologic drugs are used to target specific inflammatory mediators. Dupixent (dupilumab) was the first biologic agent approved by the FDA for the treatment of moderate-to-severe adult patients who are unresponsive to topical therapies. It binds to the IL-4 receptor and interferes with IL-13 and IL-4 signaling, which play significant roles in the pathogenesis of AD. More recently, an antibody that targets the IL-13 cytokine, Adbry (tralokinumab), has gained approval, though stronger efficacy and familiarity will ensure that Dupixent remains the first-line biologic of choice for AD.
生物制剂：生物制剂药物用于靶向特定的炎症介质。Dupixent（dupilumab）是首个获得食品药品监督管理局批准用于治疗对局部疗法无效的中重度成人患者的生物制剂。该药物通过与 IL-4 受体结合，干扰 IL-13 和 IL-4 信号传导，这些信号分子在特应性皮炎的发病机制中起重要作用。最近，一种靶向 IL-13 细胞因子的抗体 Adbry（tralokinumab）也获得了批准，但更强的疗效和临床熟悉度将确保 Dupixent 仍是特应性皮炎的首选一线生物制剂。

European guidelines (EuroGuiDerm) for systemic therapy in atopic eczema
特应性湿疹系统治疗的欧洲指南（EuroGuiDerm）

Phototherapy treatment  光疗治疗

Patients with AD can benefit from all types of light therapy, especially narrowband UVB (NB-UVB; 313nm wavelength), ultraviolet A1 (UVA1; 340–400nm), and broadband ultraviolet B (UVB; 290-320nm). Among them, NB-UVB is the most commonly used phototherapy. This treatment can be used either alone or in conjunction with topical corticosteroids or emollients. For children who fail to respond to topical therapy treatment combined with NB-UVB, phototherapy or photochemotherapy is recommended. Nevertheless, the AAD does not endorse UVA with psoralens (PUVA therapy) due to limited available evidence.
特应性皮炎（AD）患者可受益于各类光疗，尤其是窄谱 UVB（NB-UVB；波长 313nm）、长波紫外线 A1（UVA1；340-400nm）以及宽谱紫外线 B（UVB；290-320nm）。其中 NB-UVB 是最常用的光疗方式。该治疗既可单独使用，也可与外用糖皮质激素或润肤剂联合应用。对于外用治疗联合 NB-UVB 无效的儿童患者，建议采用光疗或光化学疗法。但美国皮肤病学会（AAD）因现有证据有限，不推荐使用补骨脂素联合 UVA（PUVA 疗法）。

Adjunctive treatment  辅助治疗

First-generation oral antihistamines like hydroxyzine may have a clinical advantage, mainly due to their sedating effects. Sedating antihistamines can be recommended, especially if a patient’s sleep is disturbed due to intense pruritus and starts to affect their quality of life. However, there is no strong evidence to show that the oral antihistamines address the itchy skin of AD. Therefore, non-sedating antihistamines need to be avoided.
羟嗪等第一代口服抗组胺药可能具有临床优势，主要归因于其镇静作用。尤其当患者因剧烈瘙痒导致睡眠障碍并开始影响生活质量时，可推荐使用镇静类抗组胺药。但目前尚无有力证据表明口服抗组胺药能改善 AD 的皮肤瘙痒症状，因此应避免使用非镇静类抗组胺药。

AD patients are at a higher risk of developing viral and bacterial infections, most notably impetiginization of eczema herpeticum and AD lesions. Systemic antivirals or topical or systemic antibiotics are often recommended in active secondary infection cases. Topical antimicrobial drugs, such as mupirocin, need to be limited to active bacterial skin infections and should not be recommended for routine use in AD skin that is not infected. Moreover, dilute bleach baths have been found to be effective in reducing severe symptoms of AD and can be recommended for normalizing the AD microbiome.
AD 患者发生病毒和细菌感染的风险更高，尤其是疱疹性湿疹和 AD 皮损的脓疱化。在活动性继发感染病例中，通常建议使用全身性抗病毒药物或局部/全身性抗生素。局部抗菌药物（如莫匹罗星）需仅限于活动性细菌性皮肤感染，不应推荐用于未感染的 AD 皮肤常规使用。此外，稀释漂白浴已被证明能有效减轻 AD 的严重症状，并可用于 AD 微生物群正常化。

GADA recommendations  GADA 建议

The Global Atopic Dermatitis Atlas (GADA) provides treatment recommendations following a stepped-care approach. These recommendations aim to address the entire person, considering factors beyond just the skin manifestations. The approach involves understanding triggers, addressing skin infections and wound care, and providing medical treatment along with psychosomatic counseling for moderate-to-severe patients. Mild-to-moderate patients are advised to use topical treatments, while severe patients are recommended to consider conventional systemic medicines (such as immunosuppressants) and new systemic therapies (such as biologics and oral JAK inhibitors).
全球特应性皮炎地图集(GADA)采用阶梯式治疗方案，其建议着眼于整体治疗，不仅关注皮肤症状，还综合考虑诱发因素、皮肤感染处理、伤口护理等环节。针对中重度患者，在提供治疗的同时需配合心身医学咨询；轻中度患者建议采用局部治疗，重度患者则推荐考虑传统系统药物（如免疫抑制剂）和新型系统疗法（如生物制剂与口服 JAK 抑制剂）。

Last Reviewed:  最后审阅日期：
28 May, 2024  2024 年 5 月 28 日

by Lucia Rodriguez Garcia
作者：露西亚·罗德里格斯·加西亚

Overview   概述

Methodology  方法论

We conducted an extensive literature review to identify epidemiological studies reporting the prevalence of AD in the US, Japan, and five major European markets. Searches were conducted in PubMed and Google Scholar. Potential data sources were critically appraised to provide a robust foundation on which to model and forecast the patient population of AD. We dynamically modeled the age-specific diagnosed prevalence proportions instead of using a static model, employing an in-house VBA model, as it allows for a more accurate representation of the changing prevalence rates with increasing age.
我们开展了广泛的文献综述，以识别报告美国、日本及欧洲五大主要市场特应性皮炎（AD）患病率的流行病学研究。检索工作通过 PubMed 和 Google 学术搜索引擎进行。通过对潜在数据源进行严格评估，为建模和预测 AD 患者群体奠定了可靠基础。我们采用动态建模方法分析各年龄段的诊断患病率比例，而非使用静态模型，通过自主研发的 VBA 模型实现更精准的年龄增长与患病率变化的对应关系呈现。

A recent review of AD prevalence in the pediatric population was used, which presents diagnosed 12-month prevalence (Silverberg et al., 2021). Another study was identified, which presents AD diagnosed point prevalence in adults (Barbarot et al., 2018). Point prevalence and 12-month prevalence were assumed to represent similar time periods.
近期一项针对儿童 AD 患病率的综述研究被采用（Silverberg 等，2021），该研究提供了 12 个月诊断患病率数据。另识别出 Barbarot 等（2018）关于成人 AD 时点患病率的研究。在建模中假定时点患病率与 12 个月患病率具有相似的时间代表性。

An overview of sources used is provided in the tables below.
下表汇总了所使用的数据来源概况。

Sources used for the epidemiological analysis of atopic dermatitis in adults in the US, Japan, and five major European markets, by country
美国、日本及欧洲五大主要市场成人特应性皮炎流行病学分析所用数据来源（按国家分类）

Sources used for the epidemiological analysis of atopic dermatitis in children in the US, Japan, and five major European markets, by country
美国、日本及欧洲五大主要市场儿童特应性皮炎流行病学分析所用资料来源（按国家分类）

Disease definition  疾病定义

There is no specific diagnostic test available for AD, therefore diagnosis is based solely on clinical observation of the morphology and distribution of skin lesions, related clinical signs, and historical features of atopic disease (Eichenfield et al., 2014). Multiple diagnostic criteria have been developed for AD, defining the symptoms that must be present to confirm diagnosis. Most diagnostic tests specify that the main symptoms of pruritus and eczema rash must be present over a 12-month period, along with other characteristics of AD such as elevated IgE levels and a family history of atopic disease. A validated example is the UK Working Party’s diagnostic criteria, which specify that to be diagnosed with AD, an individual must have an itchy skin condition as well as at least three of the following symptoms:
目前尚无针对特应性皮炎（AD）的特异性诊断检测方法，因此诊断完全基于对皮损形态与分布的临床观察、相关体征以及特应性疾病病史特征（Eichenfield 等学者，2014 年）。学界已制定多项 AD 诊断标准，明确确诊必须存在的症状。多数诊断标准要求瘙痒和湿疹皮疹等主要症状需持续 12 个月以上，并伴有 IgE 水平升高、特应性疾病家族史等其他 AD 特征。例如经过验证的英国工作组诊断标准规定：确诊 AD 需满足皮肤瘙痒症状，并同时具备以下至少三项特征：

• history of flexural involvement
  屈曲部位受累史

• history of asthma or hay fever
  哮喘或花粉热病史

• history of generalized dry skin
  全身性皮肤干燥史

• onset of rash under the age of two years
  两岁前出现皮疹

• visible flexural dermatitis.
  可见的屈侧皮炎

Therefore, literature was selected that classified AD cases using validated criteria to measure current symptoms.
因此，我们筛选了采用已验证标准对特应性皮炎病例进行分类以评估当前症状的文献

Country-specific methods  国别研究方法

Adults  成人患者

To estimate the prevalence of AD in adults in the US, Japan, and five major European markets, we used data from a nationally representative, cross-sectional, web-based questionnaire conducted by Barbarot et al. (2018). Adult members of online respondent panels in their respective countries were invited to participate in the study, and were blinded to the research topic. Participants were sent a questionnaire for AD symptom identification and severity assessment between February and April 2016. The questionnaire was developed based on the International Study of Asthma and Allergies in Childhood (ISAAC) questions and the UK Working Party’s diagnostic criteria for AD. Cases of AD were identified in participants who confirmed current symptoms by providing affirmative responses to core survey questions, based on ISAAC and UK Working Party diagnostic criteria. The survey also identified diagnosed cases by participant self-report of ever receiving a diagnosis for AD by a physician. This study reported diagnosed point prevalence in 2016, which was defined as cases who currently reported symptoms and had also reported diagnosis by a physician (Barbarot et al., 2018).
为估算美国、日本及欧洲五大主要市场成人特应性皮炎（AD）的患病率，我们采用了 Barbarot 等人（2018 年）开展的全国性横断面网络问卷调查数据。研究邀请各国在线受访者库中的成年成员参与，并对研究主题采取盲法设计。2016 年 2 月至 4 月期间，受试者收到用于 AD 症状识别与严重程度评估的问卷。该问卷基于《国际儿童哮喘与过敏研究》（ISAAC）问题及英国工作小组的 AD 诊断标准开发。根据 ISAAC 和英国工作小组诊断标准，对核心调查问题作出肯定答复并确认当前存在症状的参与者被判定为 AD 病例。调查还通过参与者自述曾获内科医生 AD 诊断的记录来识别确诊病例。本研究报告了 2016 年确诊时点患病率，定义为当前报告症状且曾获医师诊断的病例（Barbarot 等，2018 年）。

This study presented gender-specific and age-specific prevalence proportions separately, therefore gender ratios were calculated and applied to the age-specific rates to estimate age- and gender-specific diagnosed prevalence proportions of AD in adults. As age group data were not available for 65+ years age groups, we applied the prevalence proportion reported for the 55–65 years age group. The 15–19 years age group was assigned the prevalence proportions from the 18–24 years age group.
本研究分别呈现了按性别和年龄划分的患病率数据，因此通过计算性别比例并将其应用于各年龄段的患病率，从而估算出成人特应性皮炎（AD）按年龄和性别划分的诊断患病率。由于无法获得 65 岁以上年龄组的数据，我们采用了 55-65 岁年龄组报告的患病率。15-19 岁年龄组的患病率数据则采用了 18-24 岁年龄组的数据。

Children  儿童

To estimate the prevalence of AD in children, data from an international, cross-sectional, web-based survey of children and adolescents by Silverberg et al. (2021) were used to estimate 12-month diagnosed prevalence. Cases of AD were identified as an affirmative response to the following two definitions: (1) diagnosed as having AD according to the ISAAC criteria and self- or parent-report of ever being told by a physician that they or their child had AD (eczema); and (2) reported AD based on the ISAAC criteria only. Children (six months to 11 years old) and adolescents (12–17 years old) in each of the countries were surveyed. Recruitment of participants was initially by parents from online panels in their respective countries. To reduce selection bias, panelists were blinded to the research topic when invited (Silverberg et al., 2021).
为估算儿童特应性皮炎（AD）的患病率，本研究采用了 Silverberg 等人（2021 年）开展的跨国横断面网络调查数据，该调查对象为儿童与青少年群体，用于估算 12 个月内的确诊患病率。AD 病例的判定标准需同时满足以下两项定义：（1）根据 ISAAC 标准被诊断为 AD，且自述或家长报告曾被内科医生告知其本人或孩子患有 AD（湿疹）；（2）仅基于 ISAAC 标准报告的 AD 病例。调查覆盖各国 6 个月至 11 岁儿童及 12-17 岁青少年群体。受试者最初通过各国在线调研平台的家长渠道进行招募。为减少选择偏倚，邀请参与时未向调研对象透露研究主题（Silverberg 等，2021）。

Country-, age-, and gender-specific prevalence proportions in groups aged six months to five years old, 6–11 years, and 12–17 years were extracted from the Silverberg et al. study. As age-specific and gender-specific diagnosed prevalence proportions were presented separately, gender ratios were calculated and applied to the age-specific prevalence proportions in order to estimate age- and gender-specific prevalence proportions for each country. As the age groups did not align exactly with our five-year age groupings, the six months to five years prevalence proportion was assumed for 0–4 years, the 6–11 years prevalence proportion was assumed for 5–9 years, and the 12–17 years prevalence proportion was assumed for 10–14 years.
从 Silverberg 等人的研究中提取了针对国家、年龄和性别的患病率数据，涵盖六个月至五岁、6-11 岁及 12-17 岁人群组。由于年龄别和性别别的确诊患病率数据是分别呈现的，因此通过计算性别比例并将其应用于年龄别患病率，从而估算各国分年龄和性别的患病率。鉴于原始年龄分组与本研究采用的五年间隔年龄组不完全对应，将六个月至五岁的患病率数据对应至 0-4 岁组，6-11 岁数据对应 5-9 岁组，12-17 岁数据对应 10-14 岁组。

Forecasting  预测方法

To calculate the number of prevalent cases of AD in the 2023–43 forecast period, we multiplied prevalence proportions by the corresponding country-, age-, and gender-specific population estimates from the UN World Population Prospects database (United Nations, 2022). The UN database was chosen as a reliable population denominator; the data include standard sets of demographic indicators and populations by five-year age group and gender. The forecasted numbers of prevalent cases were validated against national benchmarks where possible, in order to check for any inconsistencies or unusual trends in the analysis.
为计算 2023-43 年预测期内阿尔茨海默病（AD）的患病人数，我们将患病率比例与联合国《世界人口展望》数据库（United Nations, 2022）中各国分年龄、性别的对应人口估算值相乘。选择联合国数据库作为可靠的人口基数来源，其数据包含标准人口统计指标及按五岁年龄组和性别划分的人口数。预测患病例数尽可能与各国基准数据进行了交叉验证，以排查分析中可能存在的矛盾或异常趋势。

Last Reviewed:  最后审阅日期：
19 Dec, 2022  2022 年 12 月 19 日

by Pamela Spicer and Sonny Nghiem
作者：帕梅拉·斯派塞与桑尼·尼姆

Overview   概述

The AD drug market will expand significantly over the 2022–31 forecast period, with sales in the US, Japan, and five major European markets increasing from $5.6bn to $16.1bn at a compound annual growth rate (CAGR) of 11.2%. AD sales in all forecasted markets are set to increase during 2022–31, driven by the growth of several targeted immunomodulators.
2022-2031 年预测期内，AD 药物市场将显著扩张，美国、日本和欧洲五大主要市场的销售额将以 11.2%的复合年增长率（CAGR）从 56 亿美元增长至 161 亿美元。在数款靶向免疫调节剂的推动下，所有预测市场的 AD 销售额均将在 2022-2031 年间持续增长。

Key themes   核心趋势

1. Approved in 2017, Dupixent enjoyed exclusivity as the sole branded systemic treatment available for AD over several years. Sanofi’s Dupixent blocks both interleukin (IL)-4 and IL-13 signaling by targeting the shared IL-4 receptor alpha. Despite increasing competition anticipated throughout the forecast period, growth is expected for this established treatment with increasing market penetration of targeted immunomodulators.
   2017 年获批的达必妥（Dupixent）作为多年来唯一可用的品牌系统性治疗药物享有市场独占权。赛诺菲的达必妥通过靶向共用的 IL-4 受体α亚基，同时阻断白细胞介素（IL）-4 和 IL-13 信号通路。尽管预测期内竞争加剧，但随着靶向免疫调节剂市场渗透率的提升，这一成熟治疗药物仍将保持增长态势。

2. The growth and entry of additional biologics will drive the bulk of the rapid expansion of the AD market during the forecast period. Directed more specifically against IL-13, lebrikizumab and tralokinumab may be viewed as more targeted approaches to treat AD. As an antibody directed against the IL-31 receptor, the focus of treatment with Mitchga (nemolizumab) will be on treating itch.
   预测期间，更多生物制剂的增长与上市将成为 AD 市场快速扩张的主要驱动力。相较于达必妥，乐伏珠单抗（lebrikizumab）和曲罗芦单抗（tralokinumab）专门针对 IL-13，可视为治疗 AD 的更精准方案。而靶向 IL-31 受体的抗体药物米替加（nemolizumab）则将聚焦于瘙痒症状的治疗。

3. Newly approved JAK inhibitors will additionally drive growth as later-line treatment options. The safety of this class has been called into question after results from the JAK inhibitor Xeljanz’s post-marketing safety study were released. Though it has been noted that elevated risks of major adverse cardiovascular events or malignancies have not been seen with other JAK inhibitors, the class is marred by this concern, which may deter dermatologists from prescribing such drugs. Nevertheless, Rinvoq has produced impressive efficacy data in its clinical trials, demonstrating superiority to Dupixent, and the oral administration of JAK inhibitors offers greater convenience compared to biologic competitors.
   新获批的 JAK 抑制剂将作为后线治疗方案进一步推动市场增长。但自从 JAK 抑制剂 Xeljanz 的上市后安全性研究结果公布后，这类药物的安全性就受到质疑。尽管有观点指出其他 JAK 抑制剂尚未观察到重大心血管不良事件或恶性肿瘤风险升高，但此类担忧仍给该类药物蒙上阴影，可能导致皮肤科医生减少处方。不过，Rinvoq 在临床试验中展现出令人瞩目的疗效数据，其表现优于 Dupixent，且与生物制剂竞品相比，JAK 抑制剂的口服给药方式更为便捷。

Methodology  方法论

Datamonitor Healthcare uses a patient-based approach to size the commercial potential of the AD treatment market across the US, Japan, and five major European markets. Our analysis contains an assessment of key therapies designed to treat AD on the market and in the late-phase pipeline, a discussion of AD market dynamics, and a 10-year patient-based sales forecast.
Datamonitor Healthcare 采用以患者为基础的分析方法，评估了美国、日本及欧洲五大主要市场特应性皮炎治疗领域的商业潜力。我们的分析包含对已上市及研发后期关键疗法的评估、特应性皮炎市场动态探讨，以及基于患者群体的十年销售预测。

Post-earnings model updates (19 December 2022)
盈利后模型更新（2022 年 12 月 19 日）

• Adbry launched in the US
  Adbry 在美国上市

• JAK inhibitors Rinvoq and Cibinqo simultaneously approved in the US and Europe
  JAK 抑制剂 Rinvoq 和 Cibinqo 在欧美同时获批上市

• JAK inhibitor Olumiant denied requested label by US FDA; US development suspended
  JAK 抑制剂 Olumiant 遭美国食品药品监督管理局拒绝标签申请；暂停在美开发

• Mitchga (nemolizumab) approved in Japan
  日本批准抗瘙痒新药 Mitchga（nemolizumab）

• AMG-451 (rocatinlimab) added, which targets the OX-40 pathway and has entered Phase III development
  新增靶向 OX-40 通路的 AMG-451（rocatinlimab）已进入 III 期临床开发阶段

• Market shares, approval dates, and pricing adjusted.
  市场份额、批准日期和定价已调整。

Biologics  生物制剂

IL-4/IL-13 antagonists  IL-4/IL-13 拮抗剂

The Th2 immune axis has been identified as a major driver in the pathogenesis of AD. Multiple antibodies employ distinct strategies to target IL-4 and IL-13, key cytokines involved in Th2-mediated pathways. By blocking the shared IL-4 receptor alpha (IL-4Rα) subunit, Dupixent inhibits the downstream signaling of both IL-13 and IL-4. On the other hand, Ebglyss neutralizes IL-13 and disrupts its binding to IL-4Rα, thereby preventing the heterodimerization of IL-4Rα and IL-13R. Adbry, which targets a different epitope of IL-13 compared to lebrikizumab, inhibits IL-13 signaling by blocking IL-13 binding to both IL-13Rα1 and IL-13Rα2, while leaving IL-4Rα unaffected.
Th2 免疫轴已被确认为特应性皮炎(AD)发病机制的主要驱动因素。多种抗体采用不同策略靶向作用于 Th2 介导通路中的关键细胞因子 IL-4 和 IL-13。Dupixent 通过阻断共用的 IL-4 受体α亚基(IL-4Rα)，同时抑制 IL-13 和 IL-4 的下游信号传导。而 Ebglyss 则通过中和 IL-13 并阻断其与 IL-4Rα结合，从而阻止 IL-4Rα与 IL-13R 形成异源二聚体。相较于 lebrikizumab，Adbry 靶向 IL-13 的不同表位，通过阻断 IL-13 与 IL-13Rα1 和 IL-13Rα2 的结合来抑制 IL-13 信号传导，同时不影响 IL-4Rα功能。

Dupixent  达必妥

• Dupixent (dupilumab) is the first-line systemic treatment of choice for AD. Most patients who receive Dupixent can be effectively managed on the drug, which is deemed safe, thus landing the product top spot in terms of clinical attractiveness among marketed drugs in our assessment model. Dermatologists are very familiar with the conjunctivitis side effect and are comfortable managing it. Commercially, Sanofi and Regeneron have secured preferred first-line access on formularies while providing exceptional support for dermatologists. Dupixent’s approval was based on the SOLO-1 and -2 studies, which showed that the proportion of adults (averaged between the studies) who achieved EASI-75 after four months was about 48% of patients treated with Dupixent dosed every other week compared to around 14% of those on placebo. The CHRONOS study revealed favorable long-term safety, along with the conjunctivitis signal. Moreover, positive results from the LIBERTY AD PEDS and PRESCHOOL studies have enabled Dupixent to gain approval in patients as young as six months old. 
  度普利尤单抗（dupilumab）是特应性皮炎（AD）的一线全身治疗首选药物。大多数接受该药物治疗的患者都能获得有效控制，且其安全性得到认可，因此在我们的评估模型中，该产品在已上市药物中临床吸引力位居榜首。皮肤科医生对其结膜炎副作用非常熟悉，并能从容应对。在商业层面，赛诺菲和再生元公司不仅确保了该药在处方集上的一线优先地位，还为皮肤科医生提供了卓越的支持。度普利尤单抗的获批基于 SOLO-1 和 SOLO-2 研究，数据显示（两项研究取平均值）接受隔周给药治疗的成人患者中，四个月后达到 EASI-75 改善标准的比例约为 48%，而安慰剂组约为 14%。CHRONOS 研究除提示结膜炎信号外，还证实了良好的长期安全性。此外，LIBERTY AD PEDS 和 PRESCHOOL 研究的积极成果使该药物获批用于低至 6 月龄的患儿。

• While Dupixent is currently the only marketed anti-IL-4 receptor antibody in China and globally, Chinese followers have emerged. With limited geographic range, these competitors have not been included in our drug assessment model. In September 2024, Keymed Biosciences has received an approval from China’s National Medical Products Administration for Kangyueda (stapokibart). The anti-IL-4Rα antibody has demonstrated a comparable efficacy profile with a much lower incidence of conjunctivitis as compared with Dupixent. Despite positive results and favorable feedback from the FDA in Q2 2024 after a Phase II study in China for rademikibart, Connect Biopharma has chosen to shift its focus in the US and Europe toward asthma and chronic obstructive pulmonary disease, moving away from AD. The company will continue its strategic partnership with Simcere Pharmaceutical for the development of rademikibart for treating AD in China.
  目前，Dupixent 是中国及全球范围内唯一上市的 IL-4 受体抗体药物，但国内已出现追随者。由于这些竞争者覆盖地域有限，尚未纳入我们的药物评估模型。2024 年 9 月，康诺亚生物旗下抗 IL-4Rα抗体药物康乐达（司普奇拜）获得中国国家药品监督管理局批准上市。该药物疗效与 Dupixent 相当，但结膜炎发生率显著降低。尽管康乃德生物在 2024 年第二季度完成中国 II 期研究的雷迪奇单抗获得美国食品药品监督管理局积极评价，该公司仍决定将欧美研发重点转向哮喘和慢性阻塞性肺疾病领域，而非特应性皮炎。在中国市场，康乃德将继续与先声药业保持战略合作，共同开发雷迪奇单抗用于特应性皮炎治疗。

“The interleukin-13s, so tralokinumab, lebrikizumab, are direct blockers of interleukin-13, which is different than Dupixent which blocks the interleukin-4 receptor blocker and then you sort of get downstream interleukin-13 blockade. They appear to have almost the same sort of side-effect profile as Dupixent. They seem to be about as effective, so I’m not really certain what the major upside’s going to be, it’s just a little bit of a mechanistic shift.” – US dermatology key opinion leader
"像 tralokinumab 和 lebrikizumab 这类 IL-13 抑制剂，是直接阻断白细胞介素-13 的，这与 Dupixent 不同——后者通过阻断 IL-4 受体来间接抑制 IL-13 通路。从现有数据看，这些新药的副作用谱与 Dupixent 几乎相同，疗效也大致相当。因此我不太确定它们的显著优势何在，只能说在作用机制上略有差异。"——美国皮肤病学领域关键意见领袖

Adbry  阿布罗单抗

• LEO Pharma’s Adbry (tralokinumab) is generally used after patients have discontinued Dupixent due to conjunctivitis, as the more targeted direct IL-13 pathway generates lower rates of this side effect. Adbry also offers the option for more flexible monthly maintenance dosing compared to Dupixent’s dosing every other week. However, this advantage does not overcome the sentiment among dermatologists that Adbry is less efficacious. In 2021, Adbry gained approval in the US and Europe to treat adults with moderate-to-severe AD based on the pivotal ECZTRA program. The ECZTRA 1 and 2 studies showed that the proportions of adults achieving EASI-75 after four months were an average of 29% of patients treated with single-agent Adbry dosed every other week compared to around 12% of those on placebo. In late 2023, Adbry received approval for use in adolescents aged 12–17 years with moderate-to-severe AD.
  LEO Pharma 公司的 Adbry（tralokinumab）通常在患者因结膜炎停用 Dupixent 后使用，因其更具靶向性的直接 IL-13 通路导致该副作用发生率较低。与 Dupixent 每两周给药方案相比，Adbry 还提供更灵活的每月维持剂量选择。然而这一优势未能改变皮肤科医生普遍认为 Adbry 疗效较弱的观点。2021 年，基于关键性 ECZTRA 项目，Adbry 获欧美批准用于治疗中重度特应性皮炎成人患者。ECZTRA 1 和 2 研究显示，接受单药 Adbry 隔周治疗的患者在四个月后达到 EASI-75 缓解标准的平均比例为 29%，而安慰剂组约为 12%。2023 年底，Adbry 获批扩展用于 12-17 岁中重度特应性皮炎青少年患者。

Ebglyss

• Results from the pivotal ADvocate trials for Ebglyss (lebrikizumab) suggest comparable efficacy to Dupixent in treating AD, with the added potential for a reduced risk of conjunctivitis. Year-long results from the ADvocate monotherapy trials also included a monthly maintenance dose. Moreover, lebrikizumab has reported positive topline data from the topical steroid add-on ADhere study. In addition to receiving approvals in Europe in 2023 and in Japan in 2024, Ebglyss was approved by the US FDA in September 2024 following the resolution of manufacturing issues. The ADvocate-1 and -2 studies showed that the proportion of patients (averaged between the studies) who achieved EASI-75 after four months was about 55% of patients treated with Ebglyss dosed every other week compared to around 17% of those on placebo. Among other studies in the Phase III program are a global study in children and adolescents (ADorable-1), an open-label long-term extension trial (ADjoin), and an open-label, single-arm, long-term adolescent trial (ADore). 
  Ebglyss（lebrikizumab）关键性 ADvocate 试验结果显示，该药物在治疗特应性皮炎方面与 Dupixent 疗效相当，且可能降低结膜炎风险。为期一年的 ADvocate 单药治疗试验还纳入了每月一次的维持剂量方案。此外，lebrikizumab 在外用皮质类固醇附加治疗的 ADhere 研究中报告了积极的顶线数据。除 2023 年在欧洲获批、2024 年在日本获批外，Ebglyss 于 2024 年 9 月获得美国食品药品监督管理局批准（此前生产问题已解决）。ADvocate-1 和-2 研究显示，隔周给药组患者治疗 4 个月后达到 EASI-75 的比例（两项研究平均值）约为 55%，而安慰剂组约为 17%。该 III 期项目还包括针对儿童和青少年的全球研究（ADorable-1）、开放标签长期扩展试验（ADjoin）以及开放标签单臂青少年长期试验（ADore）。

IL-31 antagonist  IL-31 拮抗剂

Nemluvio

• Galderma is exploring the use of anti-IL-31 receptor alpha antibody Nemluvio (nemolizumab) to address AD by targeting itch. While results from a Phase IIb trial that allowed concomitant use of topical corticosteroids showed a reduction from baseline on EASI scores over time, efficacy may be modest. Unfortunately, the monthly 30mg dose fared better than the 90mg dose, thereby not showing a clear and desired dose response. As expected, nemolizumab fared well on measures of pruritus, but the lesser effect on EASI may hinder its potential use. The pivotal ARCADIA 1 and 2 studies demonstrated modest improvements in EASI-75 scores and IGA success, with increases of 13% and 11%, respectively, in the treatment arm compared to placebo. Notably, 41% and 43% of patients in the treatment arm reported itch improvement in ARCADIA 1 and 2, respectively, versus 18% in the placebo groups. While the extent of itch improvement was numerically superior to that seen with Ebglyss, it was lower than that observed with Dupixent. After its launch in Japan as Mitchga for treating AD-related itching, Nemluvio received FDA approval for moderate-to-severe AD in adolescents and adults, and a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in December 2024.
  高德美正探索通过靶向瘙痒机制，利用抗 IL-31 受体α抗体奈莫珠单抗（Nemluvio）来治疗特应性皮炎。虽然一项允许联用外用皮质类固醇的 IIb 期试验显示，随着时间推移 EASI 评分较基线有所下降，但疗效可能较为有限。值得注意的是，每月 30mg 剂量组的表现优于 90mg 剂量组，未能呈现清晰理想的剂量反应。正如预期，奈莫珠单抗在改善瘙痒指标方面表现良好，但对 EASI 评分改善较弱可能限制其应用潜力。关键性 ARCADIA 1 和 2 研究显示，治疗组 EASI-75 评分和 IGA 成功率较安慰剂组分别提升 13%和 11%，改善幅度适中。特别值得注意的是，ARCADIA 1 和 2 研究中治疗组分别有 41%和 43%患者报告瘙痒改善，而安慰剂组仅为 18%。虽然瘙痒改善程度在数值上优于 Ebglyss，但仍低于度普利尤单抗的观察结果。 在日本以 Mitchga 品牌名上市用于治疗特应性皮炎相关瘙痒后，Nemluvio 于 2024 年 12 月先后获得美国食品药品监督管理局批准用于青少年及成人中重度特应性皮炎治疗，并收获欧洲药品管理局人用药品委员会积极审评意见。

“I think nemolizumab will be used for atopics who aren’t really atopic. So, you know, right now I use Dupixent for people with true atopic dermatitis. Atopic dermatitis, that’s an inflammatory disease that causes itch. IL-31 blockade treats itch, and so there’s people who have itch because they’re old or because they have kidney failure, or because they have liver failure, and I don’t think Dupixent’s going to work for those patients because I don’t think their itch is really related to an inflammatory atopic dermatitis. […] So, I think it might expand the market some into what I would consider non-classical forms of atopic dermatitis. I would never lie and say somebody has something when they don’t have it, but I will push the truth to the extremes for patients’ benefits.” – US dermatology key opinion leader
"我认为奈莫利珠单抗将适用于那些并非真正特应性体质的患者。目前我对确诊特应性皮炎的患者使用达必妥。特应性皮炎是一种引发瘙痒的炎症性疾病。而 IL-31 阻断剂是治疗瘙痒的，因此那些因年老、肾脏衰竭或肝脏衰竭导致瘙痒的患者，我认为达必妥对他们不会奏效，因为他们的瘙痒并非真正源于炎症性特应性皮炎。[...]所以我认为这个药物可能会将市场扩展到我所认为的非典型性特应性皮炎领域。我绝不会无中生有地诊断，但为了患者利益，我会将治疗边界推到极限。"——美国皮肤病学领域关键意见领袖

“[IL-]31s, they do have some efficacy – I mean obviously they help with itch, but they also do help with AD. The one thing you have to be careful with 31s is, if you look at some of their late-stage data, some of the patients actually had asthma exacerbations and, as you probably know, asthma, food allergies, and atopic dermatitis run on the same atopy gene. So, any drug that is going to increase asthma exacerbations you have to be careful with. It doesn’t mean we’re not going to use it, it just means you have to be careful with it. I would probably avoid it, to be honest, if you had somebody who had concomitant asthma.” – US dermatology key opinion leader
"[IL-]31 类药物确实具有一定疗效——我的意思是它们显然能缓解瘙痒，但对特应性皮炎(AD)也有帮助。使用 31 类药物时需要特别注意的是，查看其后期临床试验数据会发现，部分患者实际上出现了哮喘加重的情况。正如你可能知道的，哮喘、食物过敏和特应性皮炎都由相同的特应性基因调控。因此，任何可能加剧哮喘的药物都需要谨慎使用。这并不意味着我们不会使用它，只是需要格外小心。说实话，如果患者同时患有哮喘，我可能会避免使用这类药物。" ——美国皮肤病学关键意见领袖

OX40/OX40L antagonist  OX40/OX40L 拮抗剂

Drugs targeting OX40 are generating excitement due to robust and sustained responses. OX40, a co-stimulatory receptor on T cells, triggers the expansion and persistence of Th1, Th2, Th17, and Th22 effector and memory T cells upon activation by its ligand OX40L on antigen-presenting cells. This activation also promotes the release of cytokines, contributing to the inflammation in AD. Blocking the OX40-OX40L pathway offers a therapeutic strategy to mitigate T cell-mediated inflammation, potentially disrupting the amplification and persistence of inflammatory responses in AD. However, safety will need to be monitored as T-cell-depleting agents have been associated with an increased risk of infection and lymphoma. Additionally, Dupixent has set a high bar for efficacy and safety that will need to be cleared for market access.
靶向 OX40 的药物因其强劲且持久的疗效反应而备受瞩目。OX40 作为 T 细胞上的共刺激受体，当其被抗原呈递细胞表面的配体 OX40L 激活时，会触发 Th1、Th2、Th17 和 Th22 效应 T 细胞及记忆 T 细胞的扩增与持续存在。这种激活还会促进细胞因子的释放，从而加剧特应性皮炎（AD）的炎症反应。阻断 OX40-OX40L 通路为缓解 T 细胞介导的炎症提供了治疗策略，可能中断 AD 中炎症反应的放大与持续。但需注意监测安全性，因为 T 细胞耗竭剂与感染和淋巴瘤风险增加相关。此外，Dupixent（度普利尤单抗）在疗效和安全性方面设定了较高标准，新药需跨越这一门槛才能获得市场准入。

Rocatinlimab  罗卡坦利单抗

• Rocatinlimab, an anti-OX40 antibody, is co-developed by Amgen and Kyowa Kirin. This partnership has initiated the ROCKET program, which includes eight global Phase III studies evaluating rocatinlimab in patients with AD. Among them, the HORIZON study is testing rocatinlimab monotherapy administered as a monthly injection of an undisclosed dose. In September 2024, Amgen released topline data from the HORIZON study, revealing a 19% increase in patients achieving EASI-75 and a 13% increase in patients reaching an vIGA-AD score of 0 or 1 compared to the placebo group over 24 weeks. Although these results met co-primary endpoints with statistical significance, they are considered numerically inferior to data from Dupixent, Ebglyss, and rocatinlimab's Phase IIb study, after adjusting for their respective placebo arms. Alongside the HORIZON study, the IGNITE study is evaluating two doses of rocatinlimab monotherapy administered monthly, with trial completion estimated in February, 2025, while the SHUTTLE study examines rocatinlimab in conjunction with topical treatment, with topline readouts expected in the first half of 2025.
  罗卡替尼单抗（rocatinlimab）是一种抗 OX40 抗体，由安进（Amgen）与协和麒麟（Kyowa Kirin）联合开发。双方合作启动了名为"ROCKET"的临床项目，包含八项全球三期研究，评估该药对特应性皮炎（AD）患者的疗效。其中 HORIZON 研究采用每月一次未公开剂量的罗卡替尼单抗单药注射治疗。2024 年 9 月安进公布的 HORIZON 研究顶线数据显示：治疗 24 周后，与安慰剂组相比，达到 EASI-75 标准的患者比例提升 19%，获得 vIGA-AD 评分 0 或 1 分的患者比例增加 13%。虽然这些结果在统计学上达到了共同主要终点，但经各自安慰剂组数据校正后，其数值表现被认为逊色于达必妥（Dupixent）、Ebglyss 及罗卡替尼单抗自身 IIb 期研究的数据。除 HORIZON 研究外，IGNITE 研究正在评估两种剂量的每月单药治疗方案，预计 2025 年 2 月完成试验；而 SHUTTLE 研究则探索该药联合外用治疗的效果，顶线数据预计 2025 年上半年公布。

Amlitelimab  阿米替利单抗

• Amlitelimab is an anti-OX40L antibody initially developed by Kymab, which was subsequently acquired by Sanofi in 2021. Sanofi has published data from the Phase IIb dose-ranging STREAM-AD study evaluating the efficacy of subcutaneously administered amlitelimab in patients with AD. The results from Part 1 of the STREAM-AD study showed promising efficacy and a favorable safety profile, with 54.5% of patients achieving EASI-75 and 45.5% reaching IGA success after 24 weeks of treatment with a 250 mg monthly injection and a 500 mg loading dose, compared to 17.7% and 11.4% in the placebo group, respectively. Despite its modest placebo-adjusted efficacy, data from Part 2 suggest amlitelimab's durability. In Part 2 of the STREAM-AD study, responders were re-randomized to continue amlitelimab or withdraw for an additional 28 weeks, and high rates of EASI-75 response and IGA success were maintained in both groups, indicating the durable efficacy of amlitelimab. Throughout the 52-week study, no opportunistic or parasitic infections were reported. However, there was a slight increase in herpes cases: 4.7% in the pooled continued treatment group and 3.1% in the withdrawal group in Part 2, compared to none in the placebo group. Additionally, since 2023, Sanofi has initiated the OCEANA program, which encompasses nine Phase II and Phase III studies to further evaluate amlitelimab's efficacy in a larger patient population
  阿米替利单抗是一种抗 OX40L 抗体，最初由 Kymab 公司开发，后于 2021 年被赛诺菲收购。赛诺菲公布了评估皮下注射阿米替利单抗对特应性皮炎患者疗效的 IIb 期剂量探索研究 STREAM-AD 的数据。STREAM-AD 研究第一部分结果显示，该药物具有良好疗效和安全性——在接受每月 250 毫克注射加 500 毫克负荷剂量治疗 24 周后，54.5%患者达到 EASI-75 标准，45.5%实现 IGA 治疗成功，而安慰剂组分别为 17.7%和 11.4%。尽管其相对于安慰剂的疗效提升幅度适中，但第二部分数据表明阿米替利单抗具有持久性。在 STREAM-AD 研究第二部分中，应答者被重新随机分组继续接受治疗或停药 28 周，两组均维持较高的 EASI-75 应答率和 IGA 成功率，证实了该药物的持续有效性。在整个 52 周研究期间，未报告机会性感染或寄生虫感染病例。 然而，疱疹病例略有增加：第二部分汇总数据显示，持续治疗组发生率为 4.7%，停药组为 3.1%，而安慰剂组未出现病例。此外，自 2023 年起，赛诺菲启动了 OCEANA 项目，包含 9 项 II 期和 III 期研究，旨在更大患者群体中进一步评估 amlitelimab 的疗效

Telazorlimab  泰泽罗单抗

• Telazorlimab (ISB 830), an anti-OX40 antibody developed by Ichnos Sciences, showed low efficacy in its Phase IIb study despite favorable safety and tolerability profiles. Less than a quarter of patients in the telazorlimab arm achieved EASI-75 with 300mg every two weeks or monthly, and 25% with 600mg every two weeks, compared to 10% to 19% in the placebo arms. These results were attributed to telazorlimab’s low binding affinity to OX40. Since October 2023, Ichnos has out-licensed its OX40 antagonist antibody portfolio to Astria Therapeutics. Astria has introduced the next generation of telazorlimab, STAR-0310, which features improved characteristics, including higher affinity to OX40 (comparable to rocatinlimab), lower antibody-dependent cellular cytotoxicity compared to rocatinlimab, and a longer half-life.
  由 Ichnos Sciences 研发的抗 OX40 抗体 telazorlimab（ISB 830）在 IIb 期研究中显示出较低疗效，尽管其安全性和耐受性良好。在每两周或每月 300mg 剂量组中，仅不到四分之一患者达到 EASI-75 标准；每两周 600mg 剂量组为 25%，而安慰剂组为 10%至 19%。研究人员将这一结果归因于 telazorlimab 对 OX40 的低结合亲和力。自 2023 年 10 月起，Ichnos 已将其 OX40 拮抗剂抗体投资组合授权给 Astria Therapeutics。Astria 推出了新一代产品 STAR-0310，该药物具有改良特性：包括与 rocatinlimab 相当的更高 OX40 亲和力、更低的抗体依赖性细胞毒性以及更长的半衰期。

“There’s three different OX40s and they’re all at slightly different levels of maturity. Probably the one with the most compelling data is the Amgen molecule that’s being developed with Amgen and I think it’s Kyowa Kirin, and their data looks pretty good. The interesting thing for that particular molecule is whether it’s having a remittive effect. So, when the drug is withdrawn, patients seem to continue to respond for a prolonged period of time, which is perhaps an area that’s particularly interesting for that particular drug. There are […] fevers and chills and seemingly or presumably because of an interferon kind of drive, there are some funny side effects. It remains to be seen how well tolerated they will be.” – UK dermatology key opinion leader
目前有三种不同的 OX40 药物，它们各自处于不同的研发成熟阶段。其中安进公司与协和麒麟合作开发的分子拥有最引人注目的数据，其疗效表现相当出色。该药物最有趣的特点在于它可能具有持续缓解效应——即使停药后，患者仍能长期保持疗效反应，这一特性使该药物显得尤为独特。不过，[…]患者会出现发热、寒战等副作用，推测可能与干扰素效应有关。这些不良反应的耐受性如何仍有待观察。——英国皮肤病学领域关键意见领袖

Oral small molecules  口服小分子药物

Systemic JAK inhibitors  全身性 JAK 抑制剂

Due to cardiovascular safety concerns noted on their black box warnings, JAK inhibitors are relegated to later lines of therapy, after biologic use, by dermatologists. In 2021, oral JAK inhibitors Rinvoq and Cibinqo gained approval to treat AD in Europe and Japan, followed by US approvals in early 2022.
由于黑框警告中提及的心血管安全风险，皮肤科医生通常将 JAK 抑制剂列为生物制剂治疗后的二线选择。2021 年，口服 JAK 抑制剂 Rinvoq 和 Cibinqo 相继在欧洲和日本获批治疗特应性皮炎，并于 2022 年初获得美国监管批准。

Rinvoq   瑞福乐

• The efficacy of AbbVie’s JAK1 selective inhibitor Rinvoq (upadacitinib) is viewed most favorably in the treatment of AD. The Measure Up 1 and 2 studies showed that the proportion of adults and adolescents who achieved EASI-75 after four months averaged about 65% of patients treated with 15mg Rinvoq daily, and about 77% dosed with 30mg per day, compared to around 15% of those on placebo. The Heads Up trial showed that 41% of patients on 15mg Rinvoq achieved EASI-90 at four months as compared to 23% of patients on Dupixent, confirming the superior efficacy of Rinvoq over Dupixent on a head-to-head comparison.
  艾伯维的 JAK1 选择性抑制剂瑞福乐（乌帕替尼）在特应性皮炎治疗中的疗效最受认可。Measure Up 1 和 2 研究显示，每日服用 15 毫克瑞福乐的成人及青少年患者中，四个月后达到 EASI-75 标准的平均比例约为 65%，每日服用 30 毫克的患者比例约为 77%，而安慰剂组仅有 15%左右。Heads Up 试验表明，15 毫克瑞福乐组 41%的患者在四个月时达到 EASI-90 标准，而达必妥组仅为 23%，这证实了在头对头比较中瑞福乐疗效优于达必妥。

Cibinqo   希必可

• Pfizer’s selective JAK1 inhibitor Cibinqo (abrocitinib) has been compared to Dupixent at the lower dose, with the higher dose being potentially more efficacious at the outset of treatment. The MONO-1 and -2 studies showed that the proportion of adults and adolescents who achieved EASI-75 after three months was about 43% of patients treated with 100mg of abrocitinib daily and 62% of those dosed with 200mg per day, compared to around 11% of those on placebo. In addition to its approval in the US, Cibinqo has expanded its indication to include pediatric patients in Europe aged 12 years and older with moderate-to-severe AD.
  辉瑞公司的选择性 JAK1 抑制剂希必可（阿布昔替尼）在较低剂量下与达必妥进行了疗效对比，而较高剂量可能在治疗初期显示出更优疗效。MONO-1 和 MONO-2 研究显示：每日服用 100 毫克阿布昔替尼的成人及青少年患者中，三个月后达到 EASI-75 改善标准的比例约为 43%，而每日 200 毫克剂量组达到 62%，安慰剂组这一比例约为 11%。除在美国获批外，希必可还将其适应症扩展至欧洲 12 岁及以上中重度特应性皮炎儿科患者。

Olumiant  欧唐静

• Though Eli Lilly successfully expanded the Olumiant (baricitinib) label to include AD in Europe and Japan in 2020, the company received a CRL from the FDA and subsequently noted that there was not a role for Olumiant in treating AD in the US landscape. Provided as a supplement to a publication, the BREEZE AD-1 and -2 studies showed that the proportion of adults (averaged between the studies) who achieved EASI-75 after four months was about 18% and 23% of those treated with once-daily Olumiant 2mg and 4mg, respectively, compared to around 7% of those on placebo.
  尽管礼来公司于 2020 年成功在欧洲和日本扩展了 Olumiant（巴瑞替尼）的适应症范围，将特应性皮炎（AD）纳入其中，但该公司却收到了美国食品药品监督管理局的完全回应函（CRL），并随后指出 Olumiant 在美国市场不适用于治疗特应性皮炎。作为出版物补充资料，BREEZE AD-1 和 AD-2 研究显示，在为期四个月的治疗后，每日一次服用 2 毫克和 4 毫克 Olumiant 的成人患者中（两项研究数据取平均值），分别约有 18%和 23%的人达到了 EASI-75 缓解标准，而安慰剂组这一比例约为 7%。

“I think upadacitinib has probably and arguably the best data, but obviously upadacitinib and abrocitinib both at high dose have been trialed head-to-head against dupilumab and been shown to be superior at early time points. In the abrocitinib study it looked like dupilumab probably caught up by week 26, so the distinction – you know, I think most people would say it’s worth waiting that extra bit of time, given the safety of dupilumab.” – US dermatology key opinion leader
"我认为乌帕替尼可能拥有最具说服力的数据，但显然高剂量的乌帕替尼和阿布昔替尼都曾与度普利尤单抗进行过头对头试验，并在早期时间点显示出更优疗效。在阿布昔替尼研究中，度普利尤单抗似乎到第 26 周时疗效已基本追平——所以区别在于，考虑到度普利尤单抗的安全性，我想大多数人会认为值得多等待一段时间。"——美国皮肤病学领域关键意见领袖

Ivarmacitinib  Ivarmacitinib（伊瓦玛替尼）

• In China, late-phase studies of additional JAK inhibitors are also under way. Jiangsu Hengrui’s Reistone Biopharma reported positive topline results from the Phase III QUARTZ3 trial evaluating ivarmacitinib (SHR0302) in over 300 moderate-to-severe AD patients. Reistone touts ivarmacitinib as the first domestically developed oral JAK1 inhibitor to successfully complete a pivotal Phase III study in AD, which showed that ivarmacitinib 8mg and 4mg achieved 66% and 54% EASI-75 responses, respectively, compared to 22% for placebo, at three months. Reistone has submitted an application for Chinese approval for ivarmacitinib tablets. Ivarmacitinib is not included in the Drug Assessment Model because it is only developed in China.
  在中国，其他 JAK 抑制剂的后期研究也正在进行中。江苏恒瑞旗下瑞石生物报告了评估 ivarmacitinib（SHR0302）的 III 期 QUARTZ3 试验在 300 多名中重度 AD 患者中取得的积极顶线结果。瑞石生物宣称 ivarmacitinib 是首个成功完成 AD 关键 III 期研究的国产口服 JAK1 抑制剂，数据显示治疗三个月时，8mg 和 4mg 剂量的 ivarmacitinib 分别实现了 66%和 54%的 EASI-75 缓解率，而安慰剂组为 22%。瑞石生物已提交 ivarmacitinib 片剂的中国上市申请。由于 ivarmacitinib 仅在中国开发，因此未纳入药物评估模型。

Topical treatments  外用治疗

Topical JAK inhibitors  外用 JAK 抑制剂

Opzelura 

• Approved in 2021, topical JAK1/2 inhibitor Opzelura (ruxolitinib cream) fills the gap for a non-steroidal treatment that may be comparable to a medium potency topical corticosteroid with minimal application site burning, a common complaint with Eucrisa (along with inefficacy). Despite topical application, Incyte was unable to escape the JAK class warning that was applied to the drug’s label, though physicians understand the lowered risk as compared to systemic JAKs. In the identical Phase III TRuE-AD studies, the proportion of patients who achieved EASI-75 after two months was about 62% of patients dosed with 1.5% strength, compared to around 20% of those on vehicle.
  2021 年获批的局部 JAK1/2 抑制剂 Opzelura（鲁索替尼乳膏）填补了非甾体治疗领域的空白，其疗效可能相当于中效外用皮质类固醇，且用药部位灼烧感极低——这是 Eucrisa（同时存在疗效不足问题）常见的用药抱怨。尽管属于局部用药，但 Incyte 公司仍未能免除 JAK 类药物的标签警告，不过内科医生都明白其风险较全身性 JAK 抑制剂更低。在相同的 III 期 TRuE-AD 研究中，使用 1.5%浓度治疗两个月后达到 EASI-75 标准的患者比例约为 62%，而对照组仅为 20%左右。

“I am presently using [Opzelura] in some of my sort of mild-to-moderate patients for AD simply that are not seeing enough improvement with a topical steroid, or I’m using it as a steroid-sparing agent in sensitive areas.” – US dermatology key opinion leader
"目前我正在对一些轻度至中度特应性皮炎患者使用[Opzelura]，这些患者使用外用类固醇未见足够改善，或者我在敏感部位将其作为类固醇替代药物使用。"——美国皮肤病学关键意见领袖

Anzupgo 

• Anzupgo (delgocitinib) is a topical pan-JAK inhibitor developed by Japan Tobacco, which licensed its global rights, excluding Japan, to LEO Pharma. Marketed in Japan as Corectim ointment, it is approved for atopic dermatitis in adults (with a strength of 0.5% delgocitinib) and pediatric patients aged two to under 16 (with a strength of 0.25% delgocitinib). Globally, LEO Pharma adopted a differentiated strategy, targeting moderate-to-severe chronic hand eczema (CHE) in adults instead of competing in the crowded topicals in the atopic dermatitis market with products like Opzelura, Eucrisa, or Vtama. Anzupgo, containing 2% delgocitinib, received EU marketing authorization in September 2024 and is currently under FDA review. Approval in the EU was supported by positive results from the DELTA 1 and DELTA 2 Phase III trials, where placebo-adjusted treatment success rates at Week 16 were 10% in DELTA 1 and 22% in DELTA 2, based on the Investigator’s Global Assessment for Chronic Hand Eczema (IGA-CHE). Adverse events were well balanced between treatment and placebo arms. By focusing on chronic hand eczema, Anzupgo addresses an unmet need in a chronic condition characterized by persistent itch, redness and dryness of the hands.
  安普高（delgocitinib）是由日本烟草研发的局部泛 JAK 抑制剂，其日本以外全球权益已授权给利奥制药。该药物在日本以 Corectim 软膏上市，获批用于成人特应性皮炎（0.5% delgocitinib 浓度）及 2 岁至 16 岁以下儿童患者（0.25% delgocitinib 浓度）。利奥制药在全球市场采取差异化策略，针对成人中重度慢性手部湿疹（CHE）而非拥挤的特应性皮炎局部治疗市场（如 Opzelura、Eucrisa 或 Vtama 等竞品）。含 2% delgocitinib 的安普高于 2024 年 9 月获得欧盟上市许可，目前正在接受食品药品监督管理局审评。欧盟批准基于 DELTA 1 和 DELTA 2 两项 III 期试验的积极结果：根据慢性手部湿疹研究者整体评估（IGA-CHE），第 16 周时安慰剂校正治疗成功率在 DELTA 1 中为 10%，DELTA 2 中达 22%。治疗组与安慰剂组的不良事件发生率基本相当。 安姿普戈通过专注慢性手部湿疹领域，解决了一种以持续性瘙痒、手部发红和干燥为特征的慢性疾病中未被满足的治疗需求。

MH004

• MH004 (tofacitinib etocomil) is a topical pan-JAK inhibitor developed in China by Minghui Pharmaceuticals. The active ingredient, tofacitinib, is already known from the branded drug Xeljanz, which is approved for treating rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis via oral administration. With Xeljanz’s patent expiring in 2025 in the US, Minghui has developed a proprietary topical formulation. In a Phase III study with 377 patients, MH004 demonstrated potential, with a placebo-adjusted 38% of patients achieving EASI-75 and a placebo-adjusted 31% achieving IGA of clear or almost clear skin conditions after four weeks of treatment. This efficacy is slightly inferior but comparable to Opzelura’s Phase III results after eight weeks. As development of MH004 is limited to China, the drug is not included it in this model
  MH004（托法替尼依托考米尔）是明辉药业在中国研发的局部泛 JAK 抑制剂。其活性成分托法替尼已通过品牌药尚杰（Xeljanz）为人所知，该药获批用于口服治疗类风湿性关节炎、银屑病关节炎和溃疡性结肠炎。随着尚杰在美国的专利将于 2025 年到期，明辉药业开发了专有的局部制剂。在一项涉及 377 名患者的 III 期研究中，MH004 展现出潜力：治疗四周后，安慰剂校正后的患者中有 38%达到 EASI-75 缓解标准，31%实现皮肤症状完全或几乎完全清除（IGA 评分）。这一疗效略逊但可比拟奥普祖拉（Opzelura）八周后的 III 期结果。由于 MH004 仅在中国开发，本模型未纳入该药物。

Topical PDE4 inhibitors  局部 PDE4 抑制剂

Eucrisa   尤克里沙

• Available since 2016, Pfizer’s Eucrisa (2% crisaborole ointment) was initially one of only a few commonly used non-steroidal topical treatment options, along with topical calcineurin inhibitors Protopic (tacrolimus) and Elidel (pimecrolimus), despite poor perceived efficacy and application site burning. As such, the drug’s use is largely driven by its favorable safety profile. In 2020, Eucrisa’s US label was extended to include infants with mild-to-moderate AD aged three months and older based on positive results from the open-label CrisADe CARE 1 study.
  自 2016 年上市以来，辉瑞的尤克里沙（2%克里硼罗软膏）与局部钙调磷酸酶抑制剂他克莫司软膏和吡美莫司乳膏共同成为当时仅有的几种常用非甾体外用治疗选择，尽管其疗效感知度较低且存在用药部位灼烧感。因此，该药物的使用主要得益于其良好的安全性。2020 年，基于开放标签 CrisADe CARE 1 研究的积极结果，尤克里沙的美国说明书扩展了适应症范围，将 3 个月及以上轻度至中度特应性皮炎婴儿患者纳入其中。

Zoryve  佐瑞维

• Arcutis and AstraZeneca’s Zoryve (roflumilast) is a cream formulation of roflumilast, a potent PDE4 inhibitor considered to be more efficacious than Eucrisa. This drug also has a more favorable formulation that is associated with less burning during application. However, among topical non-steroidal options, Opzelura is seen as having high efficacy, though its twice-daily usage is less convenient than once-daily Zoryve. Zoryve demonstrated positive results in patients with AD in the INTEGUMENT studies. After one month of treatment with 0.15% roflumilast cream, 43% of patients achieved EASI-75, compared to 22% in the vehicle cream group in the INTEGUMENT-1 study, and 42% versus 20% in the INTEGUMENT-2 study. These favorable outcomes resulted in a supplemental US approval in July 2024 for Zoryve cream 0.15% in patients aged six years and older.
  Arcutis 与阿斯利康联合开发的 Zoryve（罗氟司特）是一款罗氟司特乳膏制剂，这种强效 PDE4 抑制剂被认为比 Eucrisa 疗效更佳。该药物还具备更优的制剂特性，使用时灼烧感更轻微。不过在局部外用非甾体类药物中，Opzelura 虽需每日使用两次（便利性不及每日一次的 Zoryve），但被视为高效之选。Zoryve 在 INTEGUMENT 系列研究中针对特应性皮炎患者展现出积极疗效：INTEGUMENT-1 研究显示，使用 0.15%罗氟司特乳膏治疗一个月后，43%患者达到 EASI-75 缓解标准（对照组为 22%）；INTEGUMENT-2 研究数据则为 42%对 20%。基于这些优异成果，2024 年 7 月 Zoryve 0.15%乳膏获美国 FDA 补充批准用于 6 岁及以上患者。

“I will give [Zoryve] a try. I mean obviously our experience with PDE4 agents to date in AD has been less than stellar I would say, but it is a different agent, it’s a much more potent phosphodiesterase agent, so I would give it a try. I think there may a role for it.” – US dermatology key opinion leader
"我会尝试使用[Zoryve]。虽然目前 PDE4 抑制剂在特应性皮炎领域的表现只能说差强人意，但这款药物不同——它是效力更强的磷酸二酯酶抑制剂，值得一试。我认为它应该能占有一席之地。"——美国皮肤科领域关键意见领袖

“I think ARQ-151 is very interesting in that regard and can definitely help clear up sort of mild-to-moderate psoriasis and AD patients who may have gone on to a biologic. It may capture a little bit of that group and take away from a little bit of that moderate kind of AD or moderate psoriasis population. You can use those products sort of head to toe, which is a plus. Certainly not for your severe patients, they’re going to have too high of a BSA that it’s going to be cost prohibitive. […] I see ARQ-151 being used more in kind of like your sensitive areas, maybe like a face, maybe like the groin, as just a non-steroid, just to kind of help some of those patients who might have a higher burden of disease or in cosmetically sensitive locations.” – US dermatology key opinion leader
我认为 ARQ-151 在这方面非常有趣，它肯定能帮助缓解那些可能已转向生物制剂治疗的轻中度银屑病和特应性皮炎患者。它或许能覆盖这部分人群，并分流一些中度特应性皮炎或中度银屑病患者。这类产品可以全身使用是个优势，当然不适用于重症患者——他们的体表面积过大，会导致治疗成本过高。[...]我认为 ARQ-151 更适合用于敏感部位，比如面部或腹股沟区，作为非激素类药物帮助那些疾病负担较重或治疗部位影响美观的患者。——美国皮肤病学关键意见领袖

Moizerto  莫伊泽托

• Acrotech has completed an open-label Phase III trial (ClinicalTrials.gov identifier: NCT05608343) in the US with twice-daily Moizerto (difamilast ointment 1%), which is highly selective for PDE4 subtype B. In 2021, Moizerto’s manufacturer Otsuka gained Japanese approval for the molecule as twice-daily 1% and 0.3% ointment formulations for patients aged two years and older. In a Phase III Japanese AD trial (ClinicalTrials.gov identifier: NCT03908970), the EASI-75 success rate for 1% difamilast and vehicle at one month was 43% and 13%, respectively. Additionally, an interim report of a Phase III open-label study showed that the drug demonstrated efficacy and favorable safety in Japanese infants aged three months to less than two years.
  Acrotech 公司已在美国完成了一项开放标签的 III 期临床试验（ClinicalTrials.gov 标识号：NCT05608343），该试验使用每日两次的 Moizerto（1%地法米司特软膏），该药物对 PDE4 亚型 B 具有高度选择性。2021 年，Moizerto 的生产商大冢制药在日本获得了该分子作为每日两次 1%和 0.3%软膏制剂的批准，适用于两岁及以上患者。在一项日本 AD 的 III 期临床试验中（ClinicalTrials.gov 标识号：NCT03908970），1%地法米司特和安慰剂在一个月时的 EASI-75 成功率分别为 43%和 13%。此外，一项 III 期开放标签研究的中期报告显示，该药物在三个月至两岁以下的日本婴儿中表现出疗效和良好的安全性。

Aryl hydrocarbon modulator
芳香烃受体调节剂

Vtama

Organon’s Vtama (tapinarof) is a non-steroidal topical that has demonstrated comparable efficacy to Zoryve, though Vtama has been associated with folliculitis and contact dermatitis. Vtama binds the aryl hydrocarbon receptor and gained approval to treat psoriasis in the US in May 2022. In December 2024, Vtama cream gained FDA’s approval for the treatment of AD in adults and children aged two years and older based on encouraging data from the ADORING studies. The pivotal ADORING 1 study showed that once-daily dosing of 1% tapinarof cream showed that 56% of patients in the treatment group achieved significant improvement in EASI-75 scores, compared to 23% of patients in the vehicle group. The data from ADORING 2 mirrored these positive findings. Vtama was initially developed by Dermavant for treating psoriasis and atopic dermatitis. In October 2024, Organon completed the acquisition of Dermavant, including Vtama and pipeline drugs. The acquisition agreement included an upfront payment of $175m, a $75m regulatory milestone upon US approval of Vtama for AD, and potential commercial milestones of up to $950m, including sales royalties payable to Roivant, Dermavant's parent company.
Organon 公司的 Vtama（他匹那罗夫）是一种非甾体外用药物，其疗效与 Zoryve 相当，但 Vtama 可能与毛囊炎和接触性皮炎相关。Vtama 通过结合芳烃受体发挥作用，并于 2022 年 5 月在美国获批用于银屑病治疗。2024 年 12 月，基于 ADORING 研究的积极数据，Vtama 乳膏获得美国食品药品监督管理局批准，用于治疗 2 岁及以上儿童及成人的特应性皮炎。关键性 ADORING 1 研究显示，每日一次使用 1%他匹那罗夫乳膏的治疗组中，56%患者达到 EASI-75 评分显著改善，而对照组仅为 23%。ADORING 2 研究数据也印证了这一积极结果。Vtama 最初由 Dermavant 公司开发用于治疗银屑病和特应性皮炎。2024 年 10 月，Organon 完成对 Dermavant 的收购，包括 Vtama 及其在研管线药物。收购协议包含 1.75 亿美元首付款、Vtama 获美国特应性皮炎适应症批准时 7500 万美元监管里程碑付款，以及最高可达 9.5 亿美元的潜在商业里程碑付款，其中包含需支付给 Dermavant 母公司 Roivant 的销售分成。

“Of these [novel topicals: Zoryve, Opzelura, Vtama], tapinarof gets me the most excited. […] It’s got great efficacy data, great safety data, and it has an incredible story about being derived from a bacterium that’s synergistic with a nematode that infects insects. Its mechanism of action is a conserved anti-inflammatory mechanism that crosses from insects to humans. It seems like it would be very safe and the efficacy looks good.” – US dermatology key opinion leader
“在这些[新型外用药物：Zoryve、Opzelura、Vtama]中，塔匹纳罗夫最让我感到兴奋。[…]它拥有出色的疗效数据、优异的安全性数据，并且其源自一种与感染昆虫的线虫共生细菌的故事令人惊叹。它的作用机制是一种从昆虫到人类都保守的抗炎机制。看起来它会非常安全，而且疗效表现良好。”——美国皮肤病学关键意见领袖

Despite increasing competition, Dupixent will remain dominant
尽管竞争加剧，Dupixent 仍将保持主导地位

Approved in 2017, Dupixent is regarded as safe with a known side effect of conjunctivitis that is considered tolerable. Most patients treated are effectively managed with Dupixent and, as a long-term treatment, this biologic is expected to maintain a top position in the treatment of moderate-to-severe AD patients, despite the entry of several new competitors. Additionally, Sanofi has been heralded by groups like the Institute for Clinical and Economic Review (ICER) for reasonably pricing this antibody that blocks both the IL-4 and IL-13 pathways by targeting a shared receptor. Newer drugs that target the IL-13 pathway more specifically, Ebglyss and Adbry, have not demonstrated superiority and retain the conjunctivitis side effect.
2017 年获批的 Dupixent 被认为安全性良好，其已知的结膜炎副作用尚可耐受。大多数接受该药物治疗的患者都能获得有效控制，作为长期治疗方案，这款生物制剂预计将持续占据中重度特应性皮炎患者治疗的主导地位，尽管面临多个新竞争产品的入市。此外，赛诺菲因对该抗体药物（通过靶向共享受体同时阻断 IL-4 和 IL-13 通路）的合理定价，获得了临床与经济评价研究所(ICER)等组织的赞誉。而更特异性靶向 IL-13 通路的新药 Ebglyss 和 Adbry 既未显示出疗效优势，也保留了结膜炎的副作用。

Systemic JAK inhibitors have received mixed reviews but are being met with increasing excitement
系统性 JAK 抑制剂评价褒贬不一，但正引发越来越高的关注热情

Though dermatologists remain mixed on the prospects of JAK inhibitors, this class is increasingly generating excitement because of the heterogeneity of AD and the ability of JAK inhibitors to target several key cytokines in the disease. Among the various oral candidates, AbbVie’s Rinvoq has quite impressive results. Oral JAK inhibitors are regarded with growing eagerness but also with caution by dermatologists for the treatment of AD since cardiovascular safety concerns need to be considered. Some physicians are keen to add these efficacious novel treatment options to their armamentarium, while others will hold off due to the safety concerns, thus slowing the uptake of this class.
尽管皮肤科医生对 JAK 抑制剂的前景仍存分歧，但由于特应性皮炎（AD）的异质性及 JAK 抑制剂能靶向该疾病中多种关键细胞因子的特性，这类药物正日益引发业界热情。在众多口服候选药物中，艾伯维的 Rinvoq 已展现出相当亮眼的疗效数据。皮肤科医生对口服 JAK 抑制剂治疗 AD 既抱有日益增长的期待，也保持审慎态度，因为需要考虑心血管安全性问题。部分医生迫切希望将这类高效新型疗法纳入治疗武器库，而另一些医生则会因安全性顾虑暂缓使用，这延缓了该类药物在临床的普及速度。

Excitement mounts for non-steroidal topical treatment alternatives
非甾体外用治疗替代方案正引发高涨期待

JAK1/2 inhibitor Opzelura also shows favorable data, though use of this topical formulation will be limited to patients with less body surface area involvement. Further data on systemic absorption may also be important for physicians to decide on the use of Opzelura, particularly in pediatric patients, though this drug may be an initial option to introduce and familiarize dermatologists with this class of drugs. Arcutis’s topical PDE4 inhibitor Zoryve and Dermavant’s aryl hydrocarbon modulator Vtama have also generated excitement as being potentially more efficacious than Eucrisa with less burning.
JAK1/2 抑制剂 Opzelura 也展现出积极数据，不过这种外用制剂的使用将限于体表受累面积较小的患者。关于系统吸收的进一步数据对医生决定是否使用 Opzelura 可能也很重要，尤其是儿科患者，尽管该药物或可作为皮肤科医生初步接触并熟悉此类药物的首选。Arcutis 的外用 PDE4 抑制剂 Zoryve 和 Dermavant 的芳烃受体调节剂 Vtama 同样引发关注，因其可能比 Eucrisa 疗效更佳且灼烧感更轻微。

This is a snapshot of quotes from KOLs interviewed by our analysts. To view complete interviews, access KOL Insights.
以下是我们分析师采访的关键意见领袖(KOL)的言论摘要。如需查看完整访谈，请访问 KOL 见解栏目。

The atopic dermatitis landscape is rapidly changing, with many more options for more severe patients, though unmet needs remain
特应性皮炎领域正在快速变化，虽然仍有未满足的需求，但重症患者现在有了更多治疗选择

“I think AD is sort of undergoing a revolution at the moment and for a long time we haven’t had any new therapies but suddenly there’s lots of them, either have come into clinical practice or are imminently about to come into clinical practice. So I think that the more severe population is now getting some options. I think that, however, it is a very heterogeneous disease and actually, when we look at the data of the drugs that are coming through, they don’t work for everybody. Some of the JAK kinase inhibitors are more impressive than perhaps biologics, but the JAK kinase inhibitors come with potential safety issues. So the severe population has a lot more options, either now or imminently. Some of the options are good, but there will remain 50% who are still not particularly well treated. Then I would argue that because in health economics-driven places like the UK, because many of the drugs are coming with stipulations of who can have them based on severity and so, it means that people with anything less than that severity can’t necessarily access those treatments and I think that remains hugely problematic because there’s still a massive burden of disease for which there’s no new therapies and people are still going to topical corticosteroids.” – UK dermatology key opinion leader
"我认为 AD（特应性皮炎）目前正在经历一场变革。很长一段时间里我们都没有新疗法问世，但突然间涌现出大量新药，有些已进入临床实践，有些即将投入临床应用。因此我认为重症患者现在确实获得了一些治疗选择。不过这种疾病具有高度异质性，当我们分析这些新药的数据时会发现，它们并非对所有人都有效。某些 JAK 激酶抑制剂的效果可能比生物制剂更显著，但 JAK 激酶抑制剂存在潜在的安全性问题。所以重症患者现在或即将拥有更多选择，其中部分方案效果良好，但仍有 50%的患者无法获得特别理想的治疗效果。" 那么我认为，在英国这类以卫生经济学为主导的地区，由于许多药物都附带了基于病情严重程度的使用限制条款，这意味着病情未达相应严重程度的患者未必能获得这些治疗。我认为这仍然存在极大问题，因为仍有大量疾病负担尚无新疗法应对，患者最终仍不得不依赖局部皮质类固醇。”——英国皮肤病学关键意见领袖

Dermatologists welcome JAK inhibitors as later-line options
皮肤科医生将 JAK 抑制剂视为后线治疗选择

“I think [I will use oral JAK inhibitors] in two ways. Number one, we’ve got folks that are needle averse, they just don’t want to inject and they really want to be on an oral medicine. So I think that population, obviously we would look to the JAKs because there’s really not anything else that is oral. And number two, depending on what else is out there – I mean right now we’re stuck. We really only have Dupixent and depending on what else is out there, you know it could be second or even third line depending on what happens to the IL-13s, but it could be a second- or third-line agent for someone that either there’s an AE with dupi or is just not optimally responding to Dupixent. So I don’t see the JAKs being first line, but I do think it would be nice to have a second- or third-line agent.” – US dermatology key opinion leader
“我认为[我会从两个方面使用口服 JAK 抑制剂]。首先，有些患者对针头存在抵触心理，他们就是不愿接受注射治疗，强烈希望采用口服药物。对于这类人群，显然我们会考虑 JAK 抑制剂，因为确实没有其他口服替代方案。其次，根据现有治疗选择——目前我们确实面临局限。实际上我们只有达必妥可选，而根据其他可用疗法的情况，结合 IL-13 抑制剂的疗效表现，JAK 抑制剂可能作为二线甚至三线用药。特别是对于使用达必妥出现不良反应或疗效欠佳的患者。因此我不认为 JAK 抑制剂会是一线选择，但确实需要这样的二线或三线治疗备选方案。”——美国皮肤病学领域关键意见领袖

“I’ll use IL-13s for Dupixent failures. I’ll use it before Rinvoq, I would use it before JAK inhibitors for Dupixent failure patients.” – US dermatology key opinion leader
“对于达必妥治疗失败的患者，我会优先选用 IL-13 抑制剂。在考虑使用瑞福乐或 JAK 抑制剂之前，我会先尝试 IL-13 抑制剂。”——美国皮肤病学领域关键意见领袖

“Baricitinib in particular is the least efficacious of the three [oral JAK inhibitors]. I mean that’s clear. Upa and abro are similar, I mean you’re looking at EASI-75 in the 60s, EASI-90 probably in the high 20s or 30s, something along those lines, so they’re similar. I mean obviously more experience with upa because it’s been around longer, but I think they’re going to be similar drugs at the end of the day.” – US dermatology key opinion leader
"巴瑞替尼显然是三种[口服 JAK 抑制剂]中疗效最差的。这一点很明确。乌帕替尼和阿布昔替尼效果相近，EASI-75 缓解率都在 60%左右，EASI-90 大概在 25%-30%区间，所以两者旗鼓相当。当然乌帕替尼临床应用经验更丰富，毕竟上市时间更久，但归根结底这两种药物会非常相似。" ——美国皮肤病学领域关键意见领袖

“Some JAKs work quickly but you know dupi works pretty quickly too. I mean I think the rate of onset is somewhat underrated with dupi. I mean I routinely hear people tell me that after their first shot they feel less itchy and they just feel like they’re turning the corner. You’re right, the early-onset data is much more robust with JAKs, probably for the same reason it has so many side effects, it’s much less targeted I would say than an IL-13. But yes, I think that’s true. But if somebody’s really miserable, we have other ways to control that to get them under control short-term, right? So it’s not like I need that JAK because I have nothing else that works in the short term.” – US dermatology key opinion leader
"某些 JAK 抑制剂起效确实快，但度普利尤单抗见效也不慢。其实我觉得度普利尤的起效速度被低估了。经常有患者告诉我，打完第一针就感觉瘙痒减轻，病情开始好转。你说得对，JAK 抑制剂的早期疗效数据确实更显著——这可能和它副作用较多的原因相同，相比 IL-13 抑制剂，它的靶向性要差得多。不过对于急性重症患者，我们完全有其他短期控制病情的方案，对吧？所以并非没有 JAK 抑制剂就束手无策。" ——美国皮肤病学领域关键意见领袖

“JAK inhibitors were supposed to have launched probably middle of [2021], but the FDA, of course, found that relative to TNFs in Xeljanz they had a much higher rate of MACE events and so the FDA kind of said, ‘let’s pump the breaks a little bit, we’re going to look at this a little bit more’. And in many ways, if a TNF already has a black box warning and they’re saying, ‘oh, this has a higher rate of these events,’ relative to something that already has a black box, I mean in some sense it’s almost like they’re saying it’s a double black box, right? So the safety is definitely a major concern here. The public data, based on a lot of those, at least for atopic derm, looks overwhelmingly positive from the efficacy side. We know it is highly effective, or at least most of them are. Some, of course, work better than others. You know, taking effect as soon as day two, drastic reductions in itch and having the nicety of being once-a-day sort of oral dosing. And those are all major positives.” – US dermatology key opinion leader
“JAK 抑制剂原本预计在 2021 年年中上市，但食品药品监督管理局发现，与 Xeljanz 中的 TNF 抑制剂相比，其 MACE 事件发生率要高得多，因此监管部门的态度是‘我们需要暂缓批准，进一步评估安全性’。从某种意义上说，当某种 TNF 抑制剂已带有黑框警告时，若监管机构指出新药的不良事件发生率更高，这几乎等同于双重黑框警告了。因此安全性无疑是首要考量。从公开数据来看，至少对特应性皮炎而言，这类药物的疗效数据非常积极——我们知道它们大多疗效显著，当然不同产品之间存在差异。比如用药两天即可起效，瘙痒症状大幅减轻，且具有每日一次口服给药的便利性。这些都是重大优势。”——美国皮肤病学领域关键意见领袖

“I think in the US the FDA are being a lot more cautious with the JAKs, it’s fair to say, and the change in label of Xeljanz of course and update generally to the JAK class. Then, of course, they’ve applied that label even to topical JAKs whereas I think in Europe it’s probably been a bit more relaxed, but nonetheless I think that there is clear evidence that if you feel a lower dose [of baricitinib] would work, and particularly in more elderly or vulnerable people, you wouldn’t be going to the higher dose. So I think the higher dose will get used in Europe, particularly for baricitinib because unfortunately it’s not a particularly effective drug. So at the low dose you really get very little in the way of positive impact on the skin disease.” – UK dermatology key opinion leader
"我认为在美国，食品药品监督管理局对 JAK 抑制剂类药物确实持更为谨慎的态度，公平地说，这体现在 Xeljanz 标签变更以及整个 JAK 类药物说明的更新上。当然，他们甚至将这一标签要求延伸到了外用 JAK 抑制剂，而欧洲的监管可能相对宽松些。不过我认为有明确证据表明，如果较低剂量[巴瑞替尼]就能起效，尤其是对年长或体弱患者，就没必要使用高剂量。因此我认为欧洲会继续使用高剂量，特别是巴瑞替尼，因为遗憾的是它并非特别有效的药物。在低剂量下，该药对皮肤疾病的积极影响微乎其微。"——英国皮肤病学领域关键意见领袖

“I think upadacitinib has probably and arguably the best data, but obviously upadacitinib and abrocitinib both at high dose have been trialed head-to-head against dupilumab and been shown to be superior at early time points. In the abrocitinib study it looked like dupilumab probably caught up by week 26, so the distinction – you know, I think most people would say it’s worth waiting that extra bit of time, given the safety of dupilumab.” – UK dermatology key opinion leader
“我认为乌帕替尼可能拥有最具说服力的数据，但显然高剂量的乌帕替尼和阿布昔替尼都曾与度普利尤单抗进行过头对头试验，并显示出在早期时间点的优势。在阿布昔替尼研究中，度普利尤单抗似乎在第 26 周时追平了疗效——要知道，考虑到度普利尤单抗的安全性，多数人会认为值得多等待这段时间。”——英国皮肤病学关键意见领袖

IL-13 antagonists look promising, but are unlikely to unseat Dupixent as the first-choice biologic
IL-13 拮抗剂前景可观，但不太可能取代度普利尤单抗作为首选生物制剂的地位

“I mean there’s nothing wrong with the [IL-]13s. I’m not sure there’s such a huge delta with them. I mean if you look at tralokinumab, the data’s OK. Lebrikizumab the same. I mean I don’t think it’s significantly different than what’s out there right now. Tralokinumab looks like it takes a little longer to work than the dupi arguably. Some of the week 16 data was not as good as the dupi. I mean in later time points the data is stronger, but I think dupi, again, is going to be first line over the 13s would be my guess.” – US dermatology key opinion leader
“IL-13 类药物本身没有问题，但我不认为它们存在巨大差异。以曲罗芦单抗为例，数据尚可；乐瑞珠单抗情况类似。它们与现有药物并无显著不同。曲罗芦单抗的起效时间可能比度普利尤单抗稍长，部分第 16 周数据也不及后者。虽然后期数据更强，但我认为度普利尤单抗仍将是一线选择。”——美国皮肤病学关键意见领袖

“The interleukin-13s, so tralokinumab, lebrikizumab are direct blockers of interleukin-13, which is different than Dupixent which blocks the interleukin-4 receptor blocker and then you sort of get downstream interleukin-13 blockade. They appear to have almost the same sort of side-effect profile as Dupixent. They seem to be about as effective, so I’m not really certain what the major upside’s going to be, it’s just a little bit of a mechanistic shift. But it appears safe, I certainly don’t think that they’re going to be able to unseat Sanofi/Regeneron’s sort of access right now.” – US dermatology key opinion leader
"白细胞介素-13 抑制剂如 tralokinumab 和 lebrikizumab 是直接阻断白细胞介素-13 的药物，这与 Dupixent（度普利尤单抗）通过阻断白细胞介素-4 受体从而间接抑制白细胞介素-13 的作用机制不同。这类药物似乎与 Dupixent 具有几乎相同的副作用特征，疗效也相近，因此我不太确定它们的主要优势何在，只能说在作用机制上略有差异。但安全性似乎良好，不过我认为它们目前还无法撼动赛诺菲/再生元在市场上的主导地位。"——美国皮肤病学关键意见领袖

“Tralokinumab, the data for tralokinumab is not as good as for dupilumab and it’s a drug if you respond you seem to carry on responding, but not that many people respond. The actual efficacy of it is relatively low so that’s a big problem.” – UK dermatology key opinion leader
"Tralokinumab 的临床数据表现不如 dupilumab（度普利尤单抗）。该药物的特点是如果患者产生应答，似乎能持续响应，但实际应答率并不高。其真实疗效相对较低，这是个显著问题。"——英国皮肤病学关键意见领袖

“I think lebrikizumab’s a completely different thing. I mean lebrikizumab, we wait to see the full read out of the Phase III program but the Phase II data that is in the public domain is impressive for lebrikizumab, so lebrikizumab seems to be much more on a par with dupilumab, if not marginally better in terms of EASI-50, EASI-75, and EASI-90 responses, and certainly considerably better than tralokinumab.” – UK dermatology key opinion leader
"我认为 lebrikizumab 完全是另一回事。我的意思是，虽然我们还在等待 lebrikizumab 三期项目的完整数据出炉，但已公开的二期数据显示其疗效令人印象深刻。就 EASI-50、EASI-75 和 EASI-90 应答率而言，lebrikizumab 似乎与 dupilumab 不相上下，甚至可能略胜一筹，而且明显优于 tralokinumab。"——英国皮肤病学关键意见领袖

More treatment options  更多治疗选择

There has been a huge unmet need for better treatment, particularly for long-term disease control. Current treatments such as cyclosporin, methotrexate, and azathioprine are not specific and have safety concerns. Recently, more specific treatments are becoming available for AD.
长期以来，人们对更佳治疗手段存在巨大未满足需求，尤其是针对疾病的长期控制。现有疗法如环孢素、甲氨蝶呤和硫唑嘌呤等缺乏特异性且存在安全隐患。近期，针对特应性皮炎的特异性治疗正逐渐问世。

Topical non-steroidals that are more potent
更强效的局部非甾体药物

There is a need for further non-steroidal topical therapies that are more potent. Therapies like tacrolimus, Elidel, and crisaborole can be helpful, but do not have topical corticosteroid-like efficacy. Additionally, the ideal topical drug would have higher efficacy and not involve significant burning or safety concerns. Topical JAK inhibitors are seeking to fill this gap.
市场亟需疗效更强的局部非甾体疗法。他克莫司、吡美莫司和克立硼罗等药物虽有效，但无法达到局部皮质类固醇的疗效水平。理想的局部用药应兼具更高疗效，且不会引发显著灼烧感或安全隐患。局部 JAK 抑制剂正试图填补这一空白。

Safe and effective oral therapy
安全有效的口服疗法

The need for safe and effective oral therapy options remains unmet in systemic treatments . Cyclosporin and methotrexate are moderately effective and moderately safe, but there is certainly room for safer and more effective drugs with increased EASI-90 scores and without the side effects seen with systemic JAK inhibitors, notably cardiovascular safety concerns.
在全身性治疗中，对安全有效口服疗法的需求仍未得到满足。环孢素和甲氨蝶呤虽具中等疗效与安全性，但仍有提升空间——需要能提高 EASI-90 评分、且避免全身性 JAK 抑制剂副作用（尤其是心血管安全隐患）的更安全高效药物。

Effective treatment for younger patients
针对年轻患者的有效治疗

With so many pediatric patients with AD, additional treatments are needed to safely and effectively manage the disease in this population.
鉴于众多特应性皮炎儿科患者的存在，亟需更多能安全有效控制该群体疾病的新疗法。

Predictive markers of treatment success
预测治疗成功的标志物

The measurement of treatment success in clinical trial settings is not useful in actual practice. With the potential launches of several new options, dermatologists will want better tools to guide treatment decisions as well as situations meriting combination therapy and sequential treatment regimens.
在临床试验环境中衡量治疗成功与否在实际应用中价值有限。随着多种新疗法可能即将上市，皮肤科医生将需要更好的工具来指导治疗决策，以及判断何时适合采用联合疗法和序贯治疗方案。