Delgocitinib

脂溢性皮炎是一种常见的慢性、复发性炎症性皮肤病，其发病机制复杂，涉及马拉色菌定植、皮肤屏障功能障碍、皮脂分泌异常以及免疫炎症反应等多个环节。因此，有效的药物治疗需要多管齐下，综合干预。 01 诱发因素与治疗目标 脂溢性皮炎的发病及加重受多种风险因素影响，具体见下图。 图 1 与脂溢性皮炎相关的主要因素[1] 脂溢性皮炎的治疗主要针对三个目标：控制炎症、减少马拉色菌载量和恢复皮肤屏障功能。鉴于该病的慢性复发性病程，治疗应根据受累部位、疾病严重程度和患者个体特征进行个体化制定。 02 传统治疗药物 1 外用药物 外用药物是脂溢性皮炎的基础治疗手段，根据作用机制可分为以下类别[2,3]： （1）抗真菌药 外用抗真菌药直接针对病因之一——马拉色菌过度增殖，是一线治疗药物。包括酮康唑（2% 洗发水/乳膏）、环吡酮胺（1.5% 洗发水/ 1% 乳膏）、硫化硒（2.5% 洗发水）等； 酮康唑：广谱抗真菌，能有效抑制马拉色菌，并具有一定抗炎作用。 环吡酮胺：除抗真菌外，还能抗炎并穿透角质层。 硫化硒：具有抑制真菌生长、减少皮脂分泌和轻微角质剥脱作用。 （2）糖皮质激素 短期用于急性加重期，如丙酸氯倍他索（0.05% 洗剂）、地奈德（0.05% 凝胶），避免长期使用导致皮肤萎缩； （3）钙调神经磷酸酶抑制剂（TCI） 代表药物为吡美莫司（1% 乳膏）、他克莫司（0.03%～0.1% 软膏）。对于面部、眼周等敏感薄嫩部位，或需长期间歇性维持治疗的患者，TCI 可替代外用糖皮质激素，避免其皮肤萎缩、毛细血管扩张等副作用。 其最常见不良反应为初期使用时的短暂烧灼感或刺激感，通常可耐受，且长期安全性数据良好。 （4）角质溶解剂 以水杨酸（3%～6% 溶液）为代表，适用于鳞屑厚重的病例，可与抗真菌药交替使用以提升疗效。 表 1 脂溢性皮炎的局部治疗（按解剖部位分类）[4] 2 口服药物 当局部治疗效果不佳或皮损广泛时，可考虑系统治疗，常用药物包括[5,6]： 口服异维 A 酸：低剂量使用（如隔日 10 mg），通过显著抑制皮脂腺活性、调节角质形成细胞分化及发挥抗炎作用，对伴有严重油性皮脂溢的难治性患者尤其有效。需注意其致畸等副作用。 口服抗真菌药：如伊曲康唑或氟康唑，可短期用于控制急性、广泛发作。因其潜在肝毒性等风险，不作为常规一线选择。 03 新型治疗药物 尽管传统疗法有效，但部分患者仍面临疗效不足、频繁复发或药物耐受等问题。近年来，随着对疾病免疫机制理解的深入，一系列新兴疗法为临床治疗提供了新方向。 1 磷酸二酯酶4抑制剂（PDE4 抑制剂） 磷酸二酯酶 4 抑制剂通过抑制 PDE4 酶活性，提升细胞内环磷酸腺苷（cAMP）水平，进而抑制 IL-2、IL-17、肿瘤坏死因子 -α（TNF-α）等促炎细胞因子的释放，发挥抗炎作用[7]。 0.3%罗氟司特泡沫剂或乳膏：该药物最初获批用于斑块状银屑病的治疗，近年来在脂溢性皮炎领域展现出良好应用前景，也是 FDA 第一个获批用于脂溢性皮炎的外用 PDE4 抑制剂，在临床试验中显示出良好的疗效和安全性[7,8]。 美国一项随机、双盲、安慰剂对照 Ⅲ 期临床试验使用 0.3% 罗氟司特泡沫剂治疗 304 例头皮脂溢性皮炎患者 8 周后，总有效率达 79.5%，安全性和耐受性良好，不良事件的发生率较低，且有效率远高于使用不含罗氟司特的泡沫剂对照组（153 例，58.0%）[9,10]。 该药用法为每天使用一次，可在身体的任何部位使用，包括面部和头皮等暴露部位。其刺激性比较低，具有良好的耐受性。 2%克立硼罗软膏：也是一种 PDE4 抑制剂，已在国内被批准用于轻度至中度特应性皮炎患者的治疗。该药可能对面部脂溢性皮炎或敏感皮肤有益[11]。但目前相关临床经验仅限于个案报告。 阿普米司特：一种新型的口服 PDE-4 抑制剂，在国内被批准用于适合光疗或全身治疗的中重度斑块状银屑病患者的治疗。目前病例报告显示对于反应不佳的难治性、孤立型病例有效[12]。但缺乏大规模临床数据支持。 2 生物制剂 生物制剂尚未获批用于脂溢性皮炎的治疗，仅用于特殊情况。 IL-17/IL-23抑制剂：在合并银屑病而接受 IL-17 抑制剂（如司库奇尤单抗）或 IL-23 抑制剂（如古塞奇尤单抗）治疗的患者中，临床观察发现脂溢性皮炎也随之改善，支持 Th17 通路在特定患者亚群中的潜在作用[13]。 乌司奴单抗：一项小型病例系列描述了乌司奴单抗的超说明书使用，6 名患者中有 5 名在 3～5 剂治疗后达到完全临床缓解[14]。目前，相关证据仍为个案报告。 3 JAK抑制剂 JAK-STAT 通路是多种炎症因子信号传导的共同通道。JAK 抑制剂可阻断多个炎症通路。外用及系统性 JAK 抑制剂为脂溢性皮炎的治疗提供了新的方向[15]。 ■5%芦可替尼乳膏 该药为一种小分子 JAK1/2 抑制剂，目前已获批用于治疗特应性皮炎和白癜风。虽然该药尚未正式获批用于脂溢性皮炎，但基于其药理特性，尤其适用于面部脂溢性皮炎，可视为慢性或难治性面部脂溢性皮炎的一种有前景的治疗选择。 有病例报告记录了 1.5% 外用芦可替尼成功治疗与玫瑰痤疮相关的脂溢性皮炎，说明 JAK 抑制剂在混合性或难治性炎症性皮肤病中有潜在作用[16]。然而，目前相关证据仍局限于个案报道。 ■德戈替尼 一种在日本获批使用的外用 JAK 抑制剂，适用于治疗慢性手部湿疹和特应性皮炎[17,18]。其广泛的免疫调节活性与良好的安全性特征，也显示出在治疗面部脂溢性皮炎方面的潜力[19]。 ■口服JAK抑制剂 口服 JAK 抑制剂（如乌帕替尼、阿布昔替尼、巴瑞替尼）已成为特应性皮炎的有效全身性治疗选择，对于同时合并特应性皮炎与脂溢性皮炎临床特征的患者也显示出疗效[20]。这类药物通过广泛抑制多种炎症细胞因子（IL-4、IL-13、IL-31、IL-22 和 IFN-γ），有助于快速控制炎症反应，尤其在难治性面部及头皮部位表现显著[21]。 4 微生物调节 近年来研究表明，皮肤微生物群稳态失衡是脂溢性皮炎发生与持续的重要机制之一。因此，治疗思路正从单纯抑制「有害菌」（如马拉色菌）扩展至促进「有益菌」定植、恢复皮肤微生态平衡的新方向。 益生菌：近期研究显示，外用特定益生菌（如卷曲乳杆菌、副干酪乳杆菌等）有助于减轻脂溢性皮炎的临床症状，并促进更健康的皮肤微生物组成[22]。 后生元与益生元：后生元（益生菌经加工处理后的代谢产物及菌体）和益生元（促进有益微生物生长的底物）有助于支持皮肤微生态的长期恢复[23]。 5 皮肤屏障修复治疗 皮肤屏障功能修复是脂溢性皮炎治疗的一个新方向，尤其适用于面部受累及病情反复的患者。 目前直接针对脂溢性皮炎的屏障修复证据仍然有限，但借鉴特应性皮炎的研究成果，使用含神经酰胺、胆固醇、亚油酸及烟酰胺等成分的润肤剂，被认为有助于恢复表皮完整性并减轻炎症[24]。 6 物理及化学疗法 表 2 物理及化学疗法[25] 特别说明 | 本文仅供医疗卫生等专业人士阅读 参考文献 [1]Navarro Triviño FJ, Velasco Amador JP, Rivera Ruiz I. Seborrheic Dermatitis Revisited: Pathophysiology, Diagnosis, and Emerging Therapies-A Narrative Review. Biomedicines. 2025 Oct 9;13(10):2458. doi: 10.3390/biomedicines13102458. PMID: 41153741; PMCID: PMC12562114. [2] Okokon, E.O.; Verbeek, J.H.; Ruotsalainen, J.H.; Ojo, O.A.; Bakhoya, V.N. Topical Antifungals for Seborrhoeic Dermatitis. In Cochrane Database of Systematic Reviews; Okokon, E.O., Ed.; John Wiley & Sons, Ltd.: Chichester, UK, 2015. [3] Cook, B.A.; Warshaw, E.M. Role of Topical Calcineurin Inhibitors in the Treatment of Seborrheic Dermatitis. Am. J. Clin. Dermatol. 2009, 10, 103–118. [4]Clark, G.W.; Pope, S.M.; Jaboori, K.A. Diagnosis and Treatment of Seborrheic Dermatitis. Am Fam Physician 2015, 91, 185–190 [5] de Souza Leão Kamamoto, C.; Sanudo, A.; Hassun, K.M.; Bagatin, E. Low-Dose Oral Isotretinoin for Moderate to Severe Seborrhea and Seborrheic Dermatitis: A Randomized Comparative Trial. Int. J. Dermatol. 2017, 56, 80–85. [6]Cömert, A.; Bekiroglu, N.; Gürbüz, O.; Ergun, T. Efficacy of Oral Fluconazole in the Treatment of Seborrheic Dermatitis. Am. J. Clin. Dermatol. 2007, 8, 235–238. [CrossRef] [PubMed] [7]Wang, J.; Ho, M.; Bunick, C.G. Chemical, Biochemical, and Structural Similarities and Differences of Dermatological CAMP Phosphodiesterase-IV Inhibitors. J. Investig. Dermatol. 2025, 145, 1471–1488.e1. [8] Blauvelt, A.; Draelos, Z.D.; Stein Gold, L.; Alonso-Llamazares, J.; Bhatia, N.; DuBois, J.; Forman, S.B.; Gooderham, M.; Green, L.; Guenthner, S.T.; et al. Roflumilast Foam 0.3% for Adolescent and Adult Patients with Seborrheic Dermatitis: A Randomized, Double-Blinded, Vehicle-Controlled, Phase 3 Trial. J. Am. Acad. Dermatol. 2024, 90, 986–993.  [9]Dhillon, J.; Mahajan, A.; Xie, J.; Tchack, M.; Rao, B.K. Roflumilast and the Changing Landscape of Seborrheic Dermatitis Treatment.Ann. Pharmacother. 2025. Epub ahead of print.  [10]Menta, N.; Vidal, S.I.; Friedman, A. Need for Speed: Topical Roflumilast for Rapid Control of Seborrheic Dermatitis Flares. J. Drugs Dermatol. 2025, 24, 634–635.  [11]Peña, S.M.; Oak, A.S.W.; Smith, A.M.; Mayo, T.T.; Elewski, B.E. Topical Crisaborole Is an Efficacious Steroid-sparing Agent for Treating Mild-to-moderate Seborrhoeic Dermatitis. J. Eur. Acad. Dermatol. Venereol. 2020, 34, e809–e812 [12]Cohen, S.R.; Gordon, S.C.; Lam, A.H.; Rosmarin, D. Recalcitrant Seborrheic Dermatitis Successfully Treated with Apremilast. J. Cutan. Med. Surg. 2020, 24, 90–91. [13]Mital, R.; Gray, A.; Minta, A.; Almhana, F.; Amin, S.; Hydol-Smith, J.; Mallela, T.; Kaffenberger, B.H. Novel and Off-Label Biologic Use in the Management of Hidradenitis Suppurativa, Pyoderma Gangrenosum, Lichen Planus, and Seborrheic Dermatitis: A Narrative Review. Dermatol. Ther. (Heidelb.) 2023, 13, 77–94. [14]Ghalili, S.; David, E.; Ungar, B.; Tan, K.; Lang, C.C.V.; Meariman, M.; Andrews, E.; Guttman-Yassky, E. IL-12/23-Targeting in Seborrheic Dermatitis Patients Leads to Long-Lasting Response. Arch. Dermatol. Res. 2023, 315, 2937–2940. [15]Dogra, S.; Sharma, A.; Mehta, H.; Sarkar, R. Emerging Role of Topical Janus Kinase Inhibitors in Dermatological Disorders: A Review. Clin. Exp. Dermatol. 2023, 48, 1102–1112.  [16]Pope, E.; Kowalski, E.; Tausk, F. Topical Ruxolitinib in the Treatment of Refractory Facial Seborrheic Dermatitis. JAAD Case Rep. 2022, 24, 59–60 [17]Thaçi D, Gooderham M, Lovato P, et al. Systemic exposure and bioavailability of delgocitinib cream in adults with moderate to severe Chronic Hand Eczema. J Eur Acad Dermatol Venereol. 2025;39(9):1612–1621 [18]Gooderham M, Molin S, Bissonnette R, et al. Long-term safety and efficacy of delgocitinib cream for up to 52 weeks in adults with Chronic Hand Eczema: Results of the phase 3 open-label extension DELTA 3 trial following the DELTA 1 and 2 trials. J Am Acad Dermatol. 2025;93(1):95–103 [19]Abe, M.; Igarashi, A.; Kitajima, H.; Toyama, H.; Kabashima, K.; Saeki, H. Treatment Satisfaction, Efficacy, and Safety of Delgocitinib Ointment for Atopic Dermatitis-Induced Rash on the Face and Neck: Efficacy at Reducing Local Side Effects of Topical Steroid and Tacrolimus Ointment. J. Dermatol. 2025, 52, 1232–1242  [20]He, Q.; Xie, X.; Chen, Q.; Li, W.; Song, Z.; Wang, X.; Ma, X.; Zeng, J.; Guo, J. Janus Kinase Inhibitors in Atopic Dermatitis: An Umbrella Review of Meta-Analyses. Front. Immunol. 2024, 15, 1342810.  [21]Davis, D.M.R.; Drucker, A.M.; Alikhan, A.; Bercovitch, L.; Cohen, D.E.; Darr, J.M.; Eichenfield, L.F.; Frazer-Green, L.; Paller, A.S.; Schwarzenberger, K.; et al. Guidelines of Care for the Management of Atopic Dermatitis in Adults with Phototherapy and Systemic Therapies. J. Am. Acad. Dermatol. 2024, 90, e43–e56.  [22]Paulino, L.C. New Perspectives on Dandruff and Seborrheic Dermatitis: Lessons We Learned from Bacterial and Fungal Skin Microbiota. Eur. J. Dermatol. 2017, 27, 4–7. [23]Truglio, M.; Sivori, F.; Cavallo, I.; Abril, E.; Licursi, V.; Fabrizio, G.; Cardinali, G.; Pignatti, M.; Toma, L.; Valensise, F.; et al. Modulating the Skin Mycobiome-Bacteriome and Treating Seborrheic Dermatitis with a Probiotic-Enriched Oily Suspension. Sci. Rep. 2024, 14, 2722 [24]Rajkumar, J.; Chandan, N.; Lio, P.; Shi, V. The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair. Skin Pharmacol. Physiol. 2023, 36, 174–185.  [25]王迪，张瑞珺，康玉英. 脂溢性皮炎的发病机制及治疗研究进展[J]．中华皮肤科杂志，2025, 58(1)：89-92.  投稿：wudan1@dxy.cn 题图来源：参考文献

Leo Pharma’s CEO Christophe Bourdon wants to be “the first to spot unmet needs” in medical dermatology, he said on the sidelines of the J.P. Morgan Healthcare Conference. Danish dermatology specialist Leo Pharma and its CEO Christophe Bourdon came to San Francisco to attend the J.P. Morgan Healthcare Conference for a specific reason.“I know the power of addressing unmet needs and rare diseases and how to do this,” the CEO told Fierce Pharma in a Monday interview. “That’s why we’re here at J.P. Morgan. I’m looking to add other assets in the field of rare disease.”Since taking up the helm at Leo back in 2022, Bourdon has already made waves on the dealmaking front. Last summer, Leo linked up with Boehringer Ingelheim in a deal centered on the German drugmaker's generalized pustular psoriasis drug Spevigo, worth 90 million euros ($105 million). Through that deal, BI entrusted Leo to handle further development and commercialization of a treatment for one of the few dermatology diseases that can be fatal. Leo also took on some 40 Boehringer staffers with the deal, Bourdon noted.Boehringer, which Bourdon credits with “having the vision” to pursue a rare dermatology disease, “realized it’s a great asset, but they don’t have the platform that we have,” he explained in the interview.Leo’s “unique platform” in dermatology is now a point of pride for the century-old company, which boasts “60 years of specialist expertise” in the field, according to a recent press release. Today, the drugmaker serves 100 million patients in 70 countries, but to put it simply, “every dermatologist in the world knows Leo,” the exec said.Bourdon took over at Leo in 2022 after serving in leadership roles at drugmakers including Amgen and Alexion. At the time, Leo was a struggling company in need of cost-cutting after years of taking on new debt. Now, after a strategic transformation under Bourdon’s leadership, Leo’s 8% to 10% revenue growth guidance for 2025 is a far cry from the -1% year-over-year change the drugmaker reported back in 2021. The sales turnaround came even as Leo's cost-cutting measures shrank the Danish company’s headcount from 6,000 to 4,000 in recent years.Bourdon saw, and still sees, in Leo a chance to address the 1,000 skin diseases with no approved therapies. Those untapped disease areas, he said, are difficult to diagnose as it can “take time to get in front of the right physician to have the right diagnoses.” Even if diagnosed, receiving the right level of care isn’t guaranteed. For example, only 15% to 20% of patients with moderate-to-severe atopic dermatitis are on biologics, while the remaining patients are on corticosteroids, he said. Of course, Leo isn’t the only company making moves in the medical dermatology field. Incyte, for one, was the first to market a JAK inhibitor cream in its Opzelura, although Leo’s own topical JAK Anzupgo is the only medicine of its kind that doesn’t hold a black-boxed warning, Bourdon points out. Nonetheless, more innovation only serves to drive more awareness, the CEO explained.Although he welcomes competition in the space, “I want to stay ahead of that race,” Bourdon said.“I want to be the first to spot unmet needs,” he added. “I want to be the first one to spot which mechanism could make a difference and change the standard of care for patients.”And then, the CEO says, “I want to partner up.”Partnership strategy At 2025’s iteration of the conference, Leo opened with a $1.7 billion deal with Gilead Sciences. Gilead took interest in Leo’s preclinical research programs focused on STAT6, a transcription factor used for inflammatory disease-related IL-4 and IL-13 cytokine signaling. It was “one of the largest preclinical deals ever,” Bourdon said Monday. Now, the CEO says he's hungry for “more deals” and “more partnerships.”The Spevigo deal, for one, was a new endeavor for Leo as it was “one of the first times” the company entered the field of rare diseases in medical dermatology. But Bourdon, armed with his Alexion background, is looking to expand on the initial foray. One way to widen Leo's reach in the space is by leveraging the company’s dermatologist network and development platform to advance new assets initiated by other companies, the exec said.“There are so many companies with bright ideas, but they don’t have the platform,” Bourdon emphasized.The CEO figures that that’s where Leo can step in to lead the way through approval and commercialization. To that end, the company is “getting a lot of people knocking on our door” for potential partnerships, he said.“People realized the company has completely transformed itself,” he said. “We had a bold vision three years ago, and we have delivered on it.”