Tildrakizumab-ASMN

-01- 导读 1989年，Th1和Th2细胞的二分法奠定了T细胞研究的基石。然而，2005年，董晨教授与Casey Weaver团队在《自然·免疫学》上的突破性研究，揭示了第三类T细胞亚群——Th17细胞，其以分泌IL-17为标志，彻底改写了免疫学教科书。这一发现源于对自身免疫性疾病机制的追问：为何阻断Th1/Th2通路后，炎症仍持续存在？   Th17细胞的命名源于其核心产物IL-17，而后续研究进一步明确了其分化路径：IL-6、TGF-β和IL-23等因子协同调控，驱动RORγt转录因子的表达，最终形成具有独特功能的Th17细胞。这一发现不仅解释了传统理论无法覆盖的炎症机制，更为药物研发开辟了新方向。   -02- IL-17的生物学作用：双刃剑的免疫调控 IL-17家族包括六个成员（IL-17A至IL-17F），它们通过IL-17受体（IL-17 Ra至IL-17 Re）介导其生物学功能。Th17细胞通过分泌IL-17A/F、IL-21、IL-22等细胞因子，构建了复杂的免疫网络。 1. 促炎与免疫防御 激活炎症反应：IL-17通过结合受体IL-17RA/RC，激活NF-κB、MAPK等信号通路，诱导上皮细胞、成纤维细胞等分泌IL-6、TNF-α、趋化因子（如CXCL1、CXCL8），招募中性粒细胞、单核细胞至感染或损伤部位，清除胞外病原体（如细菌、真菌）。 抗微生物屏障：促进上皮细胞分泌抗菌肽（β-防御素、S100蛋白等），增强皮肤、黏膜等物理屏障功能，抵御念珠菌、金黄色葡萄球菌等侵袭。 2. 组织修复与稳态维持 促进上皮再生：通过诱导角质形成细胞增殖和伤口愈合相关因子（如IL-22），加速皮肤、肠道等组织损伤修复。 维持肠道稳态：与IL-22协同调节肠道杯状细胞分泌黏液，保护肠道屏障完整性，防止病原体入侵。 3. 免疫调节与病理损伤 协同其他炎症因子：与TNF-α、IL-1β等协同放大炎症级联反应，在自身免疫病（银屑病、类风湿关节炎）中驱动慢性组织破坏。 介导骨代谢失衡：刺激破骨细胞分化和骨吸收，导致类风湿关节炎的骨侵蚀和银屑病关节炎的关节破坏。 动态可塑性：Th17细胞在慢性炎症中可转化为促炎的Th1样细胞，或分化为调节性Th17（分泌IL-10），影响疾病进展或缓解。 4. 肿瘤微环境调控 双重作用：在部分肿瘤中，IL-17促进血管生成（通过VEGF）和免疫抑制性微环境形成；但在特定情况下（如结肠癌），IL-17也可能增强抗肿瘤免疫应答。  -03- IL-17在自身免疫疾病中的作用 炎症性皮肤和关节疾病 IL-17在银屑病、银屑病关节炎和强直性脊柱炎的病理学中具有公认的作用。IL-17Ra或其启动子中增强IL-17应答的SNP已被确定为银屑病和强直性脊柱炎的风险因素。在银屑病皮肤病变的真皮中发现TH17细胞，并在识别CD1a呈递的自身脂质抗原后介导小鼠和人类的皮肤炎症。此外，银屑病关节炎患者的滑液中发现具有组织驻留表型的产生IL-17的CD8+T细胞。 一系列靶向IL-23/IL-17途径的治疗已经在临床上得到广泛应用。临床试验表明，靶向IL-12p40（ustekinumab）、IL-17A（secukinumab和ixekizumab）、IL-17A和IL-17F（bimekizumab）、IL-17RA（brodalumab）和IL-23（guselkumab, tildrakizumab和risankizumab）对中重度银屑病的治疗有效。靶向IL-23/IL-17途径的疗法对银屑病关节炎和强直性脊柱炎也有效。 MS和EAE 关于TH17细胞和IL-17在自身免疫疾病中的致病作用的许多初步发现是在多发性硬化症（MS）的EAE小鼠模型中获得的。最近的研究提供了令人信服的证据，证明IL-17是EAE中的关键致病细胞因子，也是MS中的主要药物靶点。 在EAE模型中，由IL-23和IL-1β或IL-18驱动的TH17细胞是介导病理学的关键T细胞群。在EAE早期，共表达αβ和γδTCR的T细胞被招募到中枢神经系统，这些高度活化的T细胞通过提供IL-17而充当炎症反应的初始触发器。 然而，也有人认为IL-17在EAE中不起主要作用。因为，在EAE的复发-缓解模型中，当在疾病诱导时或复发前给予抗IL-17单克隆抗体时，其治疗可减轻疾病，但在疾病高峰时却几乎没有效果。但是，这并不排斥IL-17可以作为MS的重要药物靶点，阻断IL-17通路可能抑制TH17细胞和γδT17细胞的诱导或再激活，这可能是预防MS患者复发的有效方法。 炎症性肠病 活动性溃疡性结肠炎或克罗恩病患者的血清和炎症粘膜中IL-17的表达显著增加。此外，GWAS研究表明，IL23R基因中的非同义SNP与克罗恩病相关。对结肠炎小鼠模型的研究表明，由TH17细胞和/或ILC产生的IL-17在慢性肠道炎症中起着关键作用。 这些研究导致了IL-17和IL-23靶向治疗炎症性肠病（IBD）的临床试验，ustekinumab已被批准用于治疗克罗恩病。然而，在IBD患者中使用secukinumab或brodalumab的临床试验导致了念珠菌感染增强和肠道炎症增加。虽然IL-17和TH17细胞可以引起炎症，从而损害肠道粘膜，但IL-17与IL-22在限制肠道真菌和细菌感染方面也起到保护作用。 其他自身免疫和炎症性疾病 对实验性自身免疫性葡萄膜炎小鼠模型的研究表明，IL-17在病理学中起着关键作用，然而在非感染性葡萄膜炎患者中使用secukinumab的临床试验未达到主要疗效终点。 此外，Th17细胞在I型糖尿病中也具有致病作用，Th17细胞在1型糖尿病患者的血液中扩增，IL-17增强人类胰岛细胞的炎症反应。用抗IL-17单克隆抗体或重组IL-25（抑制Th17细胞）治疗可减轻疾病。抗IL-12p40和抗IL-17单克隆抗体的临床试验正在1型糖尿病病人中进行。 此外，有证据表明IL-17在其他自身免疫性疾病中也发挥作用，如系统性红斑狼疮。 -04- IL-17靶向药物的开发现状 截至2025年，全球已获批的IL-17靶向药物主要包括以下五类： 司库奇尤单抗（Secukinumab）（诺华）：首个获批的IL-17A单抗（2015年），2020年销售额突破40亿美元，覆盖银屑病、银屑病关节炎（PsA）、强直性脊柱炎（AS）及化脓性汗腺炎（HS）。 依奇珠单抗（Ixekizumab）（礼来）：2016年获批，优势在于高亲和力结合IL-17A，对难治性银屑病皮损清除率（PASI 100）达44%。 布罗达单抗（Brodalumab）（安进/阿斯利康）：靶向IL-17RA受体，阻断IL-17A/F/C/E信号，2017年获批用于银屑病，对重度患者PASI 75应答率达83%。 比美吉珠单抗（Bimekizumab）（优时比）：同时中和IL-17A和IL-17F，2022年获批，临床数据显示其对银屑病的PASI 90应答率高达91%。 Netakimab（俄罗斯Biocad）：针对IL-17A，在中东欧市场占据一定份额。 国内方面，在研IL-17管线已逾50个，竞争十分激烈。目前就开发进度来看，恒瑞和智翔稳居第一梯队。2020年5月，创响生物以首付款和里程碑付款总计2.25亿美元的价格获得Izokibep在大中华区、韩国等国家和地区的独家开发和商业化权利，以及在日本以外的亚太地区进行临床开发的权利。 -05- 结语：解码免疫，点亮希望产生IL-17的T细胞和先天免疫细胞在对真菌、细菌以及病毒和寄生虫的免疫中起着关键的保护作用，但也可以介导破坏性的感染相关免疫病理学，或者通过遗传和环境因素的影响，导致自身免疫或其他慢性炎症疾病的发展。 目前，针对IL-17/IL-17R途径的治疗药物都是单克隆抗体。一些表现出明显的副作用，包括用secukinumab或Brodalumab治疗IBD患者时肠道炎症加重，用Brodalumab治疗的银屑病患者有自杀念头，以及念珠菌或上呼吸道感染加重。 由于IL-17在保护性免疫和破坏性炎症中的双重作用，另一种更具针对性的方法可能是利用宿主的天然免疫调节机制，选择性抑制IL-17对自身抗原或特定病变组织的反应。选择性诱导Treg细胞或用体外扩增的Treg细胞进行细胞治疗已经在动物模型中得到了证明，尽管尚未在人类临床试验中取得重大成功，但它们可能为治疗人类自身免疫性疾病提供了安全有效的方法。 参考文献：1.IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol.2022 Jul 5 : 1–17. 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！ 公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

The arrival of biosimilars like Celltrion's STEQEYMA and Biocon's YESINTEK is shaking up the psoriatic arthritis market, challenging blockbuster biologics with cost-effective alternatives. As competition intensifies, these biosimilars are reshaping treatment choices and driving a shift in the market landscape. LAS VEGAS, March 12, 2025 /PRNewswire/ -- Psoriatic arthritis (PsA) is a chronic inflammatory condition that affects approximately 112 per 100,000 adults worldwide. It is more prevalent in Europe and North America than in Asia and South America. In patients with psoriasis, the prevalence of psoriatic arthritis can range from 6% to 34% in Western populations. Despite its impact, many individuals with psoriatic arthritis remain undiagnosed or receive inadequate treatment, highlighting the need for increased awareness and access to specialized care. As per DelveInsight analysis, among the 7MM, the United States accounted for the highest number of prevalent cases of psoriatic arthritis in 2023, and these cases are expected to increase by the end of 2034 due to several key factors such as an increase in awareness and diagnosis, as well as the rapid prevalence of PsA. Psoriatic arthritis, occurring in approximately 20% of individuals with psoriasis, is a chronic inflammatory arthritis intricately linked to psoriatic arthritis. This aggressive condition is characterized by potential significant morbidity and compromised quality of life. Treatment approaches for psoriatic arthritis encompass a variety of strategies aimed at managing symptoms, slowing disease progression, and improving the overall quality of life. These approaches typically involve a combination of pharmacological therapies, lifestyle modifications, and, in severe cases, surgical interventions. Psoriatic arthritis treatment is highly individualized based on disease severity, response to therapy, and patient preferences, with multidisciplinary care from rheumatologists, dermatologists, and physical therapists playing a key role. Pharmacological treatment for psoriatic arthritis primarily targets inflammation and pain relief. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, are often the first line of defense, helping to reduce pain and inflammation. Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, sulfasalazine, and leflunomide are commonly prescribed to prevent joint damage and suppress the inflammatory process. For individuals with mild-to-moderate psoriatic arthritis, oral small molecules (OSMs) like OTEZLA (apremilast) offer a convenient, non-injectable option by modulating inflammatory pathways. Biologic agents have revolutionized the treatment landscape for psoriatic arthritis. These medications specifically inhibit key molecules in the inflammatory cascade. TNF inhibitors like HUMIRA (adalimumab), ENBREL (etanercept), and REMICADE (infliximab) are frontline biologics that target tumor necrosis factor, a crucial driver of inflammation. Patients who do not respond to TNF inhibitors may benefit from IL-17 inhibitors like COSENTYX (secukinumab) and TALTZ (ixekizumab) or IL-12/23 inhibitors such as STELARA (ustekinumab). Learn more about the FDA-approved psoriatic arthritis drugs @ Drugs for Psoriatic Arthritis Treatment SKYRIZI (risankizumab), developed by AbbVie, is a humanized IgG1 monoclonal antibody that acts as an interleukin-23 (IL-23) antagonist. It can be used on its own or in conjunction with non-biologic DMARDs. In June 2022, the FDA approved SKYRIZI as the first and only targeted IL-23 inhibitor for adults with active psoriatic arthritis. Another biologic, TREMFYA (guselkumab by Janssen), was approved by the FDA in July 2020 as the first monoclonal antibody that selectively binds to the p19 subunit of IL-23, further expanding treatment options for psoriatic arthritis patients. BIMZELX (bimekizumab), developed by UCB Biopharma, is a humanized monoclonal antibody that targets IL-17A and IL-17F. It received European Commission approval in June 2023 for adults with active psoriatic arthritis and axial spondyloarthritis. On September 23, 2024, the FDA approved BIMZELX for treating adults with active psoriatic arthritis, non-radiographic axial spondyloarthritis (nr-axSpA) with objective inflammation, and active ankylosing spondylitis. In Phase III studies, BIMZELX showed meaningful responses in patients with inadequate TNF inhibitor responses and those new to biologics, indicating its potential as an important treatment option for psoriatic arthritis. In cases where joint damage becomes severe and unresponsive to medical therapies, surgical interventions like joint replacement surgery may be necessary to restore function and alleviate pain. Lifestyle changes, such as regular exercise, joint protection techniques, and weight management, are also critical in managing psoriatic arthritis, as excess weight can worsen symptoms and increase disease severity. The treatment landscape for psoriatic arthritis continues to evolve, offering hope to patients with more targeted therapies and improved outcomes. As companies like UCB Biopharma, AbbVie, and Janssen advance their biologic portfolios, the future looks promising for psoriatic arthritis management. The competition in the biosimilar market is intensifying as companies introduce cost-effective alternatives to blockbuster biologics. In December 2024, Celltrion announced FDA approval for STEQEYMA (ustekinumab-stba), a biosimilar to STELARA, for subcutaneous injection or intravenous infusion in adult and pediatric patients with plaque psoriasis and psoriatic arthritis, as well as adult patients with Crohn's disease and ulcerative colitis. Simultaneously, Biocon Biologics Ltd. is strengthening its position with positive Phase III results for YESINTEK, its biosimilar to ustekinumab, in adult patients with moderate to severe chronic plaque psoriasis. The pivotal randomized, double-blind, parallel-group study demonstrated comparable efficacy and safety to the reference biologic, STELARA, and the findings are being presented at the 2025 American Academy of Dermatology (AAD) Annual Meeting in Orlando, Florida. With the approval of STEQEYMA and the promising clinical outcomes for YESINTEK, these biosimilars are poised to challenge STELARA by offering cost-effective alternatives in key immunology indications. As pricing pressures and healthcare sustainability concerns drive the demand for biosimilars, these developments mark a significant shift in the treatment landscape, providing greater accessibility and affordability for patients while increasing competition in the immunology market. To know more about psoriatic arthritis treatment options, visit @ New Treatment for Psoriatic Arthritis The psoriatic arthritis market is buzzing with numerous companies advancing treatments to cater to the growing patient base. Several therapies are expected to enter the market during the forecast period, providing new hope for patients. Some of these potential therapies include ACELYRIN Inc.'s Izokibep, Novartis Pharmaceuticals' Secukinumab, UCB Biopharma SRL's Bimekizumab, and Bristol-Myers Squibb's Deucravacitinib. Additionally, AbbVie's Upadacitinib and Risankizumab, as well as Eli Lilly and Company's Ixekizumab, are also part of the promising pipeline. Other noteworthy therapies include Sun Pharma's ILUMYA/ILUMETRI, Bristol-Myers Squibb's SOTYKTU, and Affibody's Izokibep in collaboration with Acelyrin and Inmagene. With these advancements, the psoriatic arthritis treatment landscape is set for a major shift, offering patients more tailored and effective options. The companies involved in developing biosimilars include Alvotech, Teva, Biocon Biologics, Celltrion, Fresenius Kabi, and others. Discover which therapies are expected to grab major psoriatic arthritis market share @ Psoriatic Arthritis Market Report ILUMYA/ILUMETRI by Sun Pharma is an interleukin-23 (IL-23) inhibitor classified as a humanized, anti-IL-23p19 monoclonal antibody. It works by blocking inflammatory proteins (cytokines and chemokines) in the body. By inhibiting the effects of IL-23, ILUMYA helps control the release of other inflammatory proteins, including IL-17 and TNF-α. This mechanism reduces inflammation, decreases the number of inflammatory cells in psoriatic lesions, helps prevent plaque formation, and resolves tissue damage. The drug is currently undergoing evaluation in Phase III clinical development, actively recruiting subjects with active psoriatic arthritis who have prior exposure to anti-TNF agents, as well as those who are anti-TNF naïve. SOTYKTU, developed by Bristol-Myers Squibb, is the first and only novel oral selective tyrosine kinase 2 (TYK2) inhibitor being studied across multiple immune-mediated diseases. Deucravacitinib binds to the regulatory domain of the TYK2 enzyme, inhibiting its activation. This selective inhibition reduces the release of proinflammatory cytokines and chemokines, helping to control the inflammation associated with psoriatic arthritis and alleviating its signs and symptoms. Currently, the drug is being investigated for the treatment of psoriatic arthritis in a Phase III clinical trial. Izokibep, developed by Affibody in partnership with Acelyrin and Inmagene, is a unique antibody mimetic and a novel bispecific agent that potentially targets both subunits of the IL-17A homo-dimer and serum albumin. Affibody has entered into a partnership agreement with Acelyrin for the development and commercialization of izokibep and has completed a Phase II trial. As part of this agreement, Acelyrin obtained worldwide rights to izokibep, excluding selected Asian countries, where rights have been granted to Inmagene Biopharmaceuticals. In March 2024, Acelyrin announced the release of positive top-line results from the Phase IIb/III trial, indicating that izokibep was well-tolerated with a favorable safety profile. This drug is currently in Phase III clinical trial. Discover more about drugs for psoriatic arthritis in development @ Psoriatic Arthritis Clinical Trials The anticipated launch of these emerging therapies for psoriatic arthritis is poised to transform the market landscape in the coming years. As these cutting-edge treatments continue to mature and gain regulatory approval, they are expected to reshape the psoriatic arthritis market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the psoriatic arthritis market size was USD 9 billion in 2021 and is expected to grow significantly in the coming years. This growth can be attributed to the introduction of upcoming therapies and the rising prevalence of the condition. The anticipated launch of these therapies is also expected to attract new entrants to the psoriatic arthritis market, resulting in increased competition and innovation. DelveInsight's latest published market report titled " Psoriatic Arthritis Market Insight, Epidemiology, and Market Forecast – 2034" will help you discover which market leader is set to capture the largest market share. The report provides comprehensive insights into country-specific treatment guidelines, patient pool analysis, and epidemiology forecasts to help understand key opportunities and assess the market's underlying potential. The psoriatic arthritis market report offers epidemiological analysis for the study period 2020–2034 in the 7MM, segmented into: Total Prevalent Cases of Psoriatic Arthritis Total Diagnosed Prevalent Cases of Psoriatic Arthritis Gender-specific Diagnosed Prevalent Cases of Psoriatic Arthritis Severity-specific Diagnosed Prevalent Cases of Psoriatic Arthritis The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM Psoriatic Arthritis market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this psoriatic arthritis market report to assess the epidemiology forecasts, understand patient journeys, gain insights into KOLs' opinions about upcoming treatment paradigms, and identify the factors contributing to changes in the psoriatic arthritis market. Additionally, stay informed about the mitigating factors that can enhance your market position in the psoriatic arthritis therapeutic space. Related Reports Psoriatic Arthritis Pipeline Psoriatic Arthritis Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key schizophrenia companies, including Affibody, Kymera, Selection Therapeutics GmbH, Jiangsu HengRui Medicine Co., Ltd., Nimbus Lakshmi, Inc., Hansoh BioMedical R&D Company, Bio-Thera Solutions, ACELYRIN Inc., among others. Psoriatic Arthritis Epidemiology Forecast Psoriatic Arthritis Epidemiology Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, and Psoriatic Arthritis epidemiology trends. 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About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED