评估受试制剂盐酸奥扎莫德胶囊（规格：0.92 mg（按C23H24N4O3计））与参比制剂R1盐酸奥扎莫德胶囊（ZEPOSIA®，规格：EQ 0.92 mg Base）和R2盐酸奥扎莫德胶囊（Zeposia®，规格：0.92 mg ozanimod (as hydrochloride)）在健康成年参与者空腹状态下的单中心、开放、随机、单剂量、三周期、三序列、交叉药代动力学对比试验

主要研究目的：研究空腹状态下单次口服受试制剂盐酸奥扎莫德胶囊（规格：0.92 mg（按C23H24N4O3计），四川汇宇制药股份有限公司生产）与参比制剂R1盐酸奥扎莫德胶囊（ZEPOSIA®，规格：EQ 0.92 mg Base，Celgene Corporation生产）和R2盐酸奥扎莫德胶囊（Zeposia®，规格：0.92 mg ozanimod (as hydrochloride)，Celgene Distribution B.V.生产）在健康成年参与者体内的药代动力学参数。次要研究目的：评估受试制剂盐酸奥扎莫德胶囊（规格：0.92 mg（按C？？H？？N？O？计）和参比制剂R1盐酸奥扎莫德胶囊（ZEPOSIA®，规格：EQ 0.92 mg Base，Celgene Corporation生产）和R2盐酸奥扎莫德胶囊（Zeposia®，规格：0.92 mg ozanimod (as hydrochloride)，Celgene Distribution B.V.生产）在健康成年参与者中的安全性。

开始日期2026-06-24

申办/合作机构

四川汇宇制药股份有限公司

NCT07732907

/ RecruitingN/A

Risk of Progressive Multifocal Leukoencephalopathy Among Patients With Multiple Sclerosis Exposed to Zeposia

This study will evaluate the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by John Cunningham virus (JCV), among people with multiple sclerosis who have been treated with ozanimod. The study will collect and review reported cases of PML to describe patient characteristics and estimate how often PML occurs among people treated with ozanimod. Researchers will assess factors that may be associated with the occurrence of PML, such as age, duration of ozanimod exposure, prior immunosuppressant use, lymphopenia, and JCV antibody status .

开始日期2026-06-04

申办/合作机构

Bristol Myers Squibb Co.

NCT07271069

/ RecruitingN/A

Real-world Effectiveness of Ozanimod in Patients With Steroid-Dependent Ulcerative Colitis: A Chart Review Study

The purpose of this study is to evaluate the effectiveness and safety of ozanimod vs azathioprine for the treatment of ulcerative colitis (UC) in real-world clinical practice in Japan

开始日期2026-01-29

申办/合作机构

Bristol Myers Squibb Co.

100 项与盐酸奥扎莫德相关的临床结果

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100 项与盐酸奥扎莫德相关的转化医学

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100 项与盐酸奥扎莫德相关的专利（医药）

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381

项与盐酸奥扎莫德相关的文献（医药）

2026-08-01·NEUROPHARMACOLOGY

Ozanimod and other sphingosine-1-phosphate receptor 1 modulators normalize neuropathic injury-enhanced inhibition of central lateral amygdala neurons expressing corticotropin-releasing hormone

Article

作者: Hines, Regan C ; Sheets, Patrick L ; O'Sullivan-Duffy, Abigail E

A key brain structure in the processing of chronic pain is the central nucleus of the amygdala (CeA), which has justifiably been termed the "nociceptive amygdala." Prior work shows that a major subclass of neurons in the lateral region of the CeA (CeL) expressing corticotropin-releasing hormone (CRH; CeL^CRH + neurons) is sensitized in the acute, but not chronic, stage of neuropathic pain. However, the signal transduction regulation of synaptic activity in CeL^CRH + neurons remains poorly understood. The goal of this work was to elucidate the modulation of CeL^CRH + neuron synaptic activity by sphingosine-1-phosphate receptor 1 (S1PR₁) signaling in neuropathic pain. Here we performed whole-cell patch-clamp electrophysiological recordings in acute brain slices from male mice subjected to the spared nerve injury (SNI) model of neuropathic pain to measure how pharmacological modulation of S1PR₁ alters synaptic properties of CeL^CRH + neurons. In sham, but not SNI mouse, we found S1PR₁ agonism reduced the frequency of excitatory input onto CeL^CRH + neurons, while S1PR₁ antagonism had no effect on either surgical group. We also show SNI increased the frequency of inhibitory input onto CeL^CRH + neurons which was normalized by both an S1PR₁ agonist and antagonist, as well as the clinically relevant S1PR_1,5 agonist, Ozanimod. Together, our data suggest SNI alters excitatory and inhibitory inputs onto CeL^CRH + neurons, and each type of input is differentially modulated by S1PR₁ signaling, highlighting CeL^CRH + neurons as key nodes in neuropathic pain circuitry and identifying S1PR₁s as a potential target for the development of new analgesic pharmacotherapies.

2026-08-01·ANNALS OF PHARMACOTHERAPY

Effect of Sphingosine-1-Phosphate Receptor Modulators on Insulin Resistance: A Review

Review

作者: Caíña López, Sandra ; Rodríguez Regal, Ana ; Martínez Martínez, Luciano ; Bartolomé Figueroa, Andrea

Objective::

The objective is to review the potential impact of sphingosine-1-phosphate (S1P) receptor modulators on insulin resistance in patients with multiple sclerosis, including underlying mechanisms and clinical evidence.

Data sources::

A literature search was conducted in PubMed for publications from inception through November 2025. Additional sources, including therapeutic positioning reports and official product information (Summary of Product Characteristics), were also reviewed.

Study selection and data extraction::

Relevant English and Spanish language articles were extracted and evaluated.

Data synthesis::

Sphingosine-1-phosphate receptors (S1PR) regulate both immunological and metabolic functions, representing a key therapeutic target in multiple sclerosis. Agents such as fingolimod, siponimod, ozanimod and ponesimod bind to these receptors, thereby preventing lymphocyte migration into the central nervous system. Preclinical evidence suggests that S1P signaling participates in insulin receptor and Akt pathways, affecting glycogen synthesis, glucose uptake and β-cell survival. Clinical experience, including a case of a patient with type 1 diabetes and multiple sclerosis treated with ponesimod, indicates potential increases in insulin requirements and hyperglycemia, although formal human studies are lacking.

Relevance to patient care and clinical practice::

Clinicians should monitor glycemic control in patients with multiple sclerosis receiving S1PR modulators, especially those with pre-existing metabolic disorders. Awareness of potential insulin resistance may guide drug selection and metabolic management. Further prospective studies are warranted to clarify clinical implications.

Conclusions::

S1PR modulators are effective disease-modifying therapies in multiple sclerosis, but emerging evidence suggests a possible impact on insulin signaling and glucose metabolism. Vigilance in metabolic monitoring is recommended, particularly in patients with diabetes or other risk factors for insulin resistance.

2026-07-01·JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

Asian Pacific Association of Gastroenterology (APAGE) Clinical Practice Guidelines on the Use of Small Molecules and IL‐23 p19 Inhibitors in Ulcerative Colitis and Crohn's Disease

Review

作者: Lin, Huiyu ; Ooi, Choon Jin ; Ali, Raja Affendi Raja ; Matsuoka, Katsuyoshi ; Dang, Luan Minh ; Hokari, Ryota ; Ahuja, Vineet ; Philip, Mathew ; Wan Ibrahim, Nik Razima ; Weng, Meng‐Tzu ; Hilmi, Ida ; Tan, Malcolm ; Aniwan, Satimai ; Mustaffa, Nazri ; Ng, Siew‐Chien ; Wei, Shu‐Chen ; Pisespongsa, Pises ; Limsrivilai, Julajak ; Viet, Hang Dao ; Lim, Wee‐Chian ; Simadibrata, Marcellus ; Lee, Wei Jie Jonathan ; Ling, Khoon Lin ; Leong, Rupert W. ; Kobayashi, Taku ; Sollano, Jose ; Wu, Kai Chun ; Makharia, Govind ; Mak, Joyce Wing Yan ; Ran, Zhi Hua ; Ye, Byong Duk ; Leung, Wai‐Keung ; Leow, Alex Hwong‐Ruey ; Ong, Wan Chee

ABSTRACT:

Ulcerative colitis (UC) and Crohn's disease (CD) are increasingly prevalent in the Asia Pacific region, necessitating updated, region‐specific guidance on advanced therapies. Targeted small molecule agents, such as filgotinib, tofacitinib, upadacitinib, etrasimod, and ozanimod; and the IL‐23 p19 inhibitors (guselkumab, mirikizumab, risankizumab) are the newest advanced therapies in our armamentarium for the treatment of IBD. The aim of the Asia‐Pacific consensus statements is to provide context‐specific recommendations integrating real‐world evidence specific to our region. The Asian‐Pacific Association of Gastroenterology (APAGE) Committee on Inflammatory Bowel Disease, with the participation of Asian Education Network in Inflammatory Bowel Disease (AEN‐IBD), convened a forum of 34 IBD experts from 12 countries to develop consensus guidelines on the best practices on the use of these new advanced therapies using the modified Delphi method. IL‐23 p19 inhibitors have shown good efficacy in biologic‐naïve and experienced patients in both UC and CD, with clinical and endoscopic superiority over ustekinumab and an excellent safety profile. JAK inhibitors (tofacitinib and filgotinib) are efficacious in UC, and upadacitinib is efficacious in both UC and CD. They have a rapid time to response, and emerging data on acute severe UC appears promising. However, careful screening and monitoring is needed for known side effects, and prophylactic vaccination for herpes zoster should be considered. S1P modulators (ozanimod, etrasimod) are efficacious in UC with a favorable side effect profile.

387

项与盐酸奥扎莫德相关的新闻（医药）

2026-08-10

·淘气的小一

IBD治疗药物全景解析：从Th1/Th17通路到市场格局，13大化合物的江湖地位

—— 一文读懂UC/CD生物制剂与小分子药物的疗效、安全性、机制、指南与市场 2026年8月8日 IBD · 生物制剂 · 深度分析目录疗效横评：13个化合物的UC/CD数据全景安全性分级：从黑框警告到处方信息的深度解读机制密码：Th1/Th2/Th17/TL1A轴与信号上下游指南态度：疗效分桶与一线/后线定位市场版图：2025年IBD全球销售额与竞争格局综合评估：各靶点与化合物的江湖地位结语与关键要点速览一、疗效横评：13个化合物的UC/CD数据全景以下疗效数据来源于各药物在UC和CD注册临床试验中报告的安慰剂校正有效率（药物组缓解率减去安慰剂组缓解率），旨在消除不同试验安慰剂效应的差异。1.1 UC（溃疡性结肠炎）疗效数据药物靶点诱导-应答诱导-缓解维持-应答维持-缓解综合Upadacitinib JAK1 47.5% 25.5% 46% 39% ★★★★★ Tulisokibart* TL1A 42% 25.1% — — ★★★★☆ Infliximab TNF-α 33% 26% 24% 19% ★★★★ Guselkumab IL-23 34% 15% — 30% ★★★★ Tofacitinib JAK1/3 24% 11.5% 42% 30% ★★★★ Vedolizumab α4β7 22% 12% 33% 26% ★★★★ Etrasimod S1P — 15.6% — 26% ★★★☆ Risankizumab IL-23 29% 16% — 18% ★★★ Ustekinumab IL-12/23 27% 12% 26% 19% ★★★ Ozanimod S1P 22% 12% 19% 19% ★★★ Mirikizumab IL-23 22% 10% — 22% ★★★ Adalimumab TNF-α — 7.2% — 4.4% ★★ *Tulisokibart和RO7790121为II期数据，其余为III期。数据为药物组减去安慰剂组的差值。评估时间：诱导期8-14W，维持期40-52W。1.2 CD（克罗恩病）疗效数据药物靶点诱导-应答诱导-缓解维持-应答维持-缓解综合Guselkumab IL-23 39% 34% 38% 44% ★★★★★Upadacitinib JAK1 31.5% 20.5% 34% 40% ★★★★★ Risankizumab IL-23 23% 21% 30.5% 15.5% ★★★☆ Adalimumab TNF-α 18% 14% 25% 24% ★★★★ Ustekinumab IL-12/23 19.5% 17.5% 15% 17% ★★★ Infliximab TNF-α — — — 23% ★★★ Mirikizumab IL-23 — — 23% 17% ★★★ Vedolizumab α4β7 — 8% 13% 17% ★★★ CD核心发现：Guselkumab和Upadacitinib在CD中并列最强，不分伯仲。Guselkumab诱导缓解34%/维持缓解44%，且是唯一在GALAXI头对头试验中优于Ustekinumab的IL-23抑制剂。Upadacitinib维持缓解40%同样突出。但Upadacitinib对结肠型CD疗效显著，对回肠型CD不显著有效。二、安全性分级：从黑框警告到处方信息深度解读2.1 安全性黑框警告对比药物靶点黑框警告安全评级 Tofacitinib JAK1/3 严重感染+血栓栓塞+恶性肿瘤+全因死亡率↑⚠⚠⚠⚠ 最高 Upadacitinib JAK1 严重感染+血栓栓塞+恶性肿瘤+全因死亡率↑⚠⚠⚠⚠ 最高 Infliximab TNF-α 严重感染+恶性肿瘤（淋巴瘤、HSTCL）⚠⚠⚠ 高 Adalimumab TNF-α 严重感染+恶性肿瘤（淋巴瘤、HSTCL）⚠⚠⚠ 高 Ozanimod S1P 1/5 无（需监测心脏传导、黄斑水肿） ⚠ 低-中 Etrasimod S1P 1/4/5 无（需监测心脏传导、肝功能） ⚠ 低-中 Ustekinumab IL-12/23 p40 无 ⚠ 低-中 Guselkumab IL-23 p19 无✓ 低 Risankizumab IL-23 p19 无✓ 低 Mirikizumab IL-23 p19 无✓ 低Vedolizumabα4β7无（肠道选择性，安全性最优）✓✓✓✓ 最安全2.2 为什么Ustekinumab（IL-12/23）安全性弱于IL-23 p19抑制剂？这是一个关键的靶点选择性差异。Ustekinumab靶向IL-12和IL-23的共享p40亚基，因此同时阻断IL-12/Th1和IL-23/Th17两条通路。而Guselkumab/Risankizumab/Mirikizumab仅靶向IL-23的p19亚基，保留IL-12/Th1保护性免疫通路。① Ustekinumab处方信息中的独特警告（IL-23 p19抑制剂中没有的）安全性条目UstekinumabIL-23 p19抑制剂说明恶性肿瘤 (5.4)✗ 有✓ 无 Ustekinumab："STELARA® may increase risk of malignancy"PRES (5.6)✗ 有✓ 无后部可逆性脑病综合征非感染性肺炎 (5.9)✗ 有✓ 无间质性肺炎、嗜酸性粒细胞肺炎、隐源性机化性肺炎特定感染风险 (5.2)✗ 有✓ 无 IL-12遗传缺陷患者易感分枝杆菌、沙门氏菌、BCG② IL-23 p19抑制剂的独特关注点（Ustekinumab中没有强调的）安全性条目IL-23 p19抑制剂Ustekinumab说明肝毒性 (5.4)✗ IBD中需常规监测一般性提示 Guselkumab≥16周/Mirikizumab≥24周/Risankizumab报告过DILI伴皮疹安全性结论：IL-23 p19选择性抑制剂（Guselkumab、Risankizumab、Mirikizumab）的安全性优于Ustekinumab。原因：(1) 保留IL-12/Th1保护性免疫，无恶性肿瘤、PRES、非感染性肺炎警告；(2) 处方信息安全性条目仅5条 vs Ustekinumab 9条。IL-23 p19的肝毒性虽需监测，但可逆且可控。Vedolizumab仍是安全性标杆（肠道选择性，无系统性免疫抑制）。三、机制密码：Th1/Th2/Th17/TL1A轴与信号上下游3.1 免疫应答分化框架 CD4⁺ T细胞分化通路初始 CD4⁺ T细胞 ↙ ↓ ↘ Th1 亚群IL-12 驱动分化 Th2 亚群IL-4 驱动分化 Th17 亚群TGF-β + IL-6 驱动IL-23 维持存活 ↓ ↓ ↓ 效应因子IFN-γ · TNF-α 效应因子IL-4 · IL-5 · IL-13 效应因子IL-17A/F · IL-22 ↓ ↓ ↓ 细胞免疫细胞内病原体防御巨噬细胞活化体液免疫寄生虫防御过敏反应黏膜防御上皮屏障保护抗真菌/细菌 CD ≈ Th1 / Th17 混合型透壁性肉芽肿性炎症 UC ≈ Th2样 / Th17 混合型黏膜层连续性炎症3.2 TNF-α抑制剂为什么适合关节类疾病？ TNF-α是RA、AS、PsA等关节疾病的核心致病因子。在滑膜组织中驱动细胞增生、破骨细胞活化、软骨降解。局限：Adalimumab在UC中疗效偏弱（缓解仅7.2%）；系统性免疫抑制带来严重感染和恶性肿瘤风险。3.3 IL-23 vs IL-17：同一通路，截然不同的肠道命运 IL-23抑制剂皮肤 ✓ 银屑病、PsA有效肠道 ✓ CD、UC有效上游阻断，同时下调IL-17、IL-22、GM-CSF 保留IL-12/Th1保护性通路 IL-17抑制剂皮肤 ✓ 银屑病"神药"(Cosentyx 2025年销61亿美元) 肠道 ✗ CD中反而加重疾病 IL-17在肠道是"保护性"的：促进抗菌肽、维持紧密连接核心教训：Secukinumab在CD中不仅无效，反而加重疾病。IL-17在肠黏膜中发挥"保护性"作用。IL-23抑制剂设计更优：上游阻断多个效应通路，不影响IL-17的屏障保护功能。3.4 Ustekinumab vs IL-23 p19：为什么p19更安全？靶向范围对比：p40（广谱）vs p19（精准） Ustekinumab（抗 IL-12/23 p40 亚基）阻断范围：p40IL-12 + IL-23 双阻断 ↓ Th1 ↓+ Th17 ↓ ↓ 保护性免疫受损感染风险 ↑ 肿瘤风险 ↑ PRES非感染性肺炎恶性肿瘤警告 VS IL-23 p19 抑制剂（Guselkumab · Risankizumab · Mirikizumab）阻断范围：p19仅阻断 IL-23 ↓ Th1 保留 ✓+ Th17 ↓ ↓ 保护性免疫保留风险显著更低无 PRES无非感染性肺炎无恶性肿瘤警告 ✓ IL-23 p19 选择性抑制剂安全性显著优于 Ustekinumab —— 保留 IL-12 / Th1 保护性免疫，独有的肝毒性可控可逆3.5 JAK抑制剂：为什么关节、肠道、皮肤都适合？ Upadacitinib选择性抑制JAK1，可同时阻断Th1（IFN-γ）、Th2（IL-4/IL-13）、Th17相关炎症（IL-6信号），覆盖所有T细胞亚群——这就是其疗效最强的原因。安全代价：同时抑制抗病毒、造血、免疫监视等生理通路，黑框警告最重。3.6 S1P受体调节剂：为什么更适合UC？ S1P调节剂将淋巴细胞"困"在淋巴结中。UC炎症局限于黏膜层，阻断淋巴细胞归巢即可控制；CD是透壁性炎症，单纯阻断迁移可能不足。3.7 Vedolizumab为什么是最安全的？ Vedolizumab：肠道选择性"锁-钥"阻断机制核心逻辑：α4β7 整合素（钥匙）只在肠道淋巴细胞上 → MAdCAM-1（锁）只在肠道血管上 → Vedolizumab 堵住钥匙 = 仅肠道免疫被抑制 ▎钥匙与锁的分布：仅肠道一对一匹配 🔑 钥匙：α4β7 整合素表达位置肠道归巢淋巴细胞只在 → 肠道淋巴细胞表面受体决定它"回哪个家" ↔ 🔒 锁：MAdCAM-1 表达位置仅肠道黏膜血管内皮只在 → 肠道血管内皮"门禁"识别α4β7并放行 α4β7 钥匙→ MAdCAM-1 锁→ 肠道炎症 ↑ 正常生理：这把锁-钥配对让免疫细胞精准进入肠道巡逻，维持黏膜免疫稳态。IBD 中过度激活。 ▎Vedolizumab 介入：堵住钥匙，锁-钥失效 α4β7被占据 Vedolizumab人源化抗α4β7单抗 ⊘ 占据钥匙 ✕ MAdCAM-1无法结合→ 肠道炎症↓ ↓ ↓ ▎为什么肠道之外不受影响？不同的器官用不同的锁-钥 ✗ 肠道 α4β7 ↔ MAdCAM-1Vedolizumab 阻断 → 免疫受抑制 ✓ 大脑/关节/皮肤 α4β1 ↔ VCAM-1Vedolizumab 不结合 → 免疫正常运转 ✓ 肺/呼吸道 αEβ7 ↔ E-cadherinVedolizumab 不结合 → 免疫正常运转核心结论：α4β7 特异性拮抗 = 仅肠道免疫被抑制，不碰 α4β1/VCAM-1（大脑/关节/皮肤）和 αEβ7/E-cadherin（肺），因此严重感染和恶性肿瘤风险 ≈ 安慰剂水平，成为 IBD 安全性标杆。3.8 Th2型药物为什么不适合肠道？呼吸道黏膜需要"防尘口罩" Th2主导，嗜酸性粒细胞+IgE IL-4/IL-13是核心驱动肠道黏膜需要"海关+边防军" Th1/Th17主导，巨噬细胞+中性粒细胞面对100万亿共生细菌黏膜 ≠ 肠道黏膜——不同组织需求不同的免疫策略。3.9 TL1A抑制剂：为什么是下一个"王炸"？ TL1A（TNFSF15）通过功能性受体DR3和诱饵受体DcR3发挥效应，在IBD中扮演多维度核心角色：① 同时放大Th1、Th17和Th2应答与IL-12协同：放大Th1应答（IFN-γ↑）与IL-23协同：放大Th17应答（IL-17↑）独立放大Th2应答：驱动IL-4、IL-5、IL-13 还能激活2型固有淋巴细胞（ILC2）这意味着TL1A抑制剂可同时调控CD（Th1/Th17主导）和UC（Th2样/Th17混合型）。② 独一无二：同时调控炎症与纤维化 TL1A — 唯一同时调控炎症与纤维化的双通路靶点通路一：炎症放大（共刺激分子） TL1A+ IL-12 → Th1 ↑IFN-γ↑ TL1A+ IL-23 → Th17 ↑IL-17↑ TL1A独立 → Th2 ↑ + ILC2 ↑IL-4/5/13↑ CD (Th1/17)+ UC (Th2样/17)均被 TL1A 驱动通路二：纤维化调控（独立于炎症） TL1A 过表达基因工程模型 → 成纤维细胞活化胶原沉积肠壁增厚 → 肠道纤维化肠腔狭窄 ↓ 抗 TL1A 抗体已建立纤维化 → 组织学逆转 ✓恢复至炎症前水平临床关联：CD患者外周血TL1A水平 ↑ → 与小肠狭窄、肠狭窄程度正相关 | GWAS：TNFSF15多态性 → CD/UC易感性现有药物仅抗炎vs TL1A 抑制剂抗炎 + 抗纤维化双通路调控 ★ 所有现有IBD药物仅作用于炎症通路，TL1A是唯一同时阻断炎症放大 + 逆转纤维化的靶点。CD最大未满足需求——纤维化狭窄——首次有了机制层面的解决方案。 CD最大未满足需求是肠道纤维化导致的狭窄——现有所有药物均不能逆转纤维化。TL1A是唯一同时调控炎症和纤维化的靶点。③ 遗传学证据多项GWAS发现TNFSF15多态性与CD和UC易感性相关。④ 地位预测基于II期ARTEMIS-UC数据（诱导缓解25.1%，接近Upadacitinib），若III期延续：CD纤维化/狭窄型首选之一，UC中与JAK抑制剂争夺最强疗效且可能更安全。默沙东108亿+罗氏71亿重注。四、指南态度：疗效分桶与一线/后线定位 2024年AGA发布UC动态指南，2025年发布CD动态指南，核心创新是按疗效将药物分桶（efficacy buckets），并区分初治和经治患者。4.1 UC指南中的药物定位（AGA 2024）① 对所有中重度UC患者——是否使用推荐强度药物说明强推荐 Infliximab, Golimumab, Vedolizumab, Ustekinumab, Ozanimod, Etrasimod, Risankizumab, Guselkumab 证据中-高强推荐* Tofacitinib*, Upadacitinib* *FDA限TNF失败/不耐受条件性推荐 Adalimumab, Filgotinib*, Mirikizumab 证据中等② 对初治患者——疗效分桶疗效层级药物高效 Infliximab, Vedolizumab, Ozanimod, Etrasimod, Risankizumab, Guselkumab (Upadacitinib*限TNF失败后)中效 Golimumab, Ustekinumab, Tofacitinib*, Filgotinib*, Mirikizumab低效 Adalimumab③ 对TNF经治失败患者——疗效分桶疗效层级药物高效 Tofacitinib, Upadacitinib, Ustekinumab中效 Filgotinib, Mirikizumab, Risankizumab, Guselkumab低效 Adalimumab, Vedolizumab, Ozanimod, Etrasimod UC指南核心：JAK抑制剂虽在初治中列为高效，但FDA标签限制TNF失败后使用——实际非真正一线。Adalimumab在UC归为低效。Vedolizumab、Infliximab和IL-23 p19抑制剂是真正的一线高效选择。4.2 CD指南中的药物定位（AGA 2025）① 对所有中重度CD患者——是否使用推荐强度药物强推荐 Infliximab, Adalimumab, Ustekinumab, Risankizumab, Mirikizumab, Guselkumab强推荐* Upadacitinib* (*FDA限TNF失败后)条件性推荐 Certolizumab pegol, Vedolizumab② 对初治患者——疗效分桶疗效层级药物高效 Infliximab, Adalimumab, Vedolizumab, Ustekinumab, Risankizumab, Mirikizumab, Guselkumab低效 Certolizumab pegol, Upadacitinib (回肠型CD不显著有效)③ 对TNF经治失败患者——疗效分桶疗效层级药物高效 Adalimumab, Risankizumab, Guselkumab, Upadacitinib中效 Ustekinumab, Mirikizumab低效 Vedolizumab, Certolizumab pegol CD指南核心：(1) Vedolizumab在CD仅条件性推荐，TNF失败后归为低效。(2) Upadacitinib初治CD归低效（回肠型不显著），TNF失败后升级高效。(3) AGA仅1项强推荐，9项条件性推荐，6项知识空白。五、市场版图：近5年IBD全球销售额与竞争格局5.1 IBD适应症上市时间线 IBD 生物制剂 & 小分子药物上市时间线 1998Infliximab→CDIBD生物制剂时代开启 2005Infliximab→UC 2007Adalimumab→CD 2012Adalimumab→UC — TNF-α 抑制剂 14 年垄断期 — 2014Vedolizumab→UC + CD肠道选择性里程碑 2016Ustekinumab→CD 2018Tofacitinib→UC首个IBD口服小分子 2019Ustekinumab→UC — 小分子与新一代生物制剂爆发期 — 2021Ozanimod→UC 2022Upadacitinib→UC/Risankizumab→CD 2023Upadacitinib→CD/Mirikizumab→UC/Etrasimod→UC 2024Risankizumab→UC/Guselkumab→UC 2025Guselkumab→CD/Mirikizumab→CD 2025年：IBD 领域 5 大靶点、13+ 药物同台竞技，进入精准治疗时代5.2 2025年IBD全球销售额与趋势分析排名药物靶点2025年IBD销售额（估）趋势1Vedolizumab (Entyvio) α4β7~61亿美元↑ 稳健增长2Risankizumab (Skyrizi) IL-23~56亿美元↑↑ 快速放量3Ustekinumab (Stelara) IL-12/23~46亿美元↓↓ 类似药暴跌 4 Upadacitinib (Rinvoq) JAK1 ~22亿美元↑↑ 快速增长 5 Infliximab (Remicade+类似药) TNF-α ~18亿美元↓ 持续萎缩 6 Guselkumab (Tremfya) IL-23 ~12亿美元↑↑↑ 刚放量 7 Adalimumab (Humira+类似药) TNF-α ~10亿美元↓↓ 类似药冲击 8 Mirikizumab (Omvoh) IL-23 ~3亿美元↑ 爬坡中 9 Tofacitinib (Xeljanz) JAK1/3 ~1.5亿美元↓ 边缘化 10 Ozanimod (Zeposia) S1P ~1.4亿美元 — 11 Etrasimod (Velsipity) S1P ~1亿美元↑ 爬坡中注：Vedolizumab 100%来自IBD。Risankizumab IBD占比约32%（总销售175亿，UC+CD放量）。Ustekinumab IBD占比约75%（总额60.8亿，类似药冲击暴跌）。Infliximab含原研+生物类似药总市场。Adalimumab含原研+生物类似药。① 增长与下降的核心驱动因素 Vedolizumab（↑ 稳健增长）：作为唯一100%来自IBD的药物，增长动力来自安全性口碑驱动的处方前移+SC剂型渗透。2025年仍为IBD领域处方量第一品牌。 Risankizumab（↑↑ 快速放量）：2022年获批CD、2024年获批UC，双适应症驱动+银屑病基础患者转化。2025年总销售175亿美元（全适应症），IBD贡献~56亿，同比增长~27%。艾伯维指引2027年IBD将达75亿美元。 Ustekinumab（↓↓ 暴跌）：2023年IBD峰值~76亿美元，2024年专利到期后生物类似药大规模进入欧美市场，2025年总额骤降至60.8亿，IBD贡献~46亿。未来将持续萎缩。 Upadacitinib（↑↑ 快速增长）：UC+CD双适应症+口服便利性驱动。但FDA标签限制TNF失败后使用，增长天花板受安全标签制约。 Infliximab/Adalimumab（↓ 持续萎缩）：生物类似药竞争+新靶点药物替代。Infliximab原研仅17.7亿（类似药占68%市场份额），Adalimumab原研仅45.4亿（全适应症）。 Guselkumab（↑↑↑ 刚放量）：2024年9月获批UC、2025年3月获批CD，2025年总销售51.6亿（+40.5%），IBD贡献刚起步但增长潜力巨大。② Vedolizumab的SC剂型与口服给药潜力 Vedolizumab的增长很大程度上受益于皮下注射（SC）剂型的推出。根据武田2025年Q3财报，美国市场SC（Entyvio Pen）与IV的体量比约为90% IV : 10% SC，但SC患者数季度环比双位数增长，且已获得全美三大PBM的处方覆盖。2024年4月SC剂型获FDA批准用于CD维持治疗，进一步扩大了SC适用人群。 SC剂型对Vedolizumab销售额增长的重要性体现在：(1) 提高患者依从性——居家自注射免去了每8周一次的输液中心就诊；(2) 降低医疗机构负担——输液位资源有限，SC释放了产能瓶颈；(3) 延长产品生命周期——SC专利保护期晚于IV，可延缓生物类似药冲击（IV专利2030年左右到期，SC专利更长）。然而，SC仍需注射给药。口服给药在IBD领域的潜力值得关注——S1P受体调节剂（Ozanimod、Etrasimod）和JAK抑制剂（Upadacitinib、Tofacitinib）已实现口服给药，且Upadacitinib展现了最强疗效。未来口服α4β7小分子抑制剂（如Morphic的MORF-057，礼来32亿美元收购，吉利德的GS-1427）若能复制Vedolizumab的安全性优势同时实现口服给药，将对Vedolizumab的市场地位构成实质性挑战——这正是各大药企竞相布局的方向。③ 市场排序背后的应用场景与临床价值从2025年IBD销售额排序中，可以清晰地读出各靶点在不同应用场景中的临床价值定位：市场排序药物/靶点核心应用场景临床价值定位第1梯队(>50亿) Vedolizumab (α4β7)Risankizumab (IL-23)长期维持治疗（Vedolizumab安全性最优）初治一线+经治（Risankizumab疗效+安全兼顾） Vedolizumab = 维持期金标准Risankizumab = 新一代中坚力量第2梯队(20-50亿) Ustekinumab (IL-12/23)Upadacitinib (JAK1)正在退场（Ustekinumab类似药冲击）TNF失败后/口服偏好（Upadacitinib疗效最强但安全受限） Ustekinumab = 退位中的老一代龙头Upadacitinib = 疗效天花板，安全标签限使用第3梯队(10-20亿) Infliximab (TNF-α)Guselkumab (IL-23)CD穿透型/瘘管型/急性重症（Infliximab不可替代）CD初治一线（Guselkumab头对头胜Stelara） Infliximab = 经典基石，特定场景不可替代Guselkumab = CD最强新星，增长潜力巨大第4梯队(<10亿) Adalimumab, MirikizumabTofacitinib, Ozanimod, EtrasimodCD炎症型（Adalimumab）UC口服偏好（Ozanimod/Etrasimod）UC后线（Tofacitinib限TNF失败后）各有细分场景，但增长空间有限或受安全标签制约市场洞察：销售额排序直接反映了临床价值的层级——安全+疗效兼顾的药物（Vedolizumab、Risankizumab）占据第1梯队；疗效极强但安全受限的药物（Upadacitinib）受标签制约停留在第2梯队；特定场景不可替代的药物（Infliximab在CD穿透型）虽总量萎缩但维持刚需。未来，若TL1A抑制剂和口服α4β7抑制剂上市，这一格局将被重新改写。5.3 2025年IBD市场份额格局 2025年全球IBD市场规模约200亿美元（含原研+生物类似药）。靶点类别代表药物2025年IBD销售额（估）趋势IL-12/23 + IL-23 Stelara/Skyrizi/Tremfya/Omvoh ~115亿 Skyrizi接棒Stelaraα4β7整合素 Entyvio ~61亿 IBD销冠，稳增长TNF-α Remicade/Humira ~28亿持续萎缩JAK Rinvoq/Xeljanz ~24亿 Upadacitinib增长S1P Zeposia/Velsipity ~2.4亿渗透率低六、综合评估：各靶点与化合物的江湖地位6.1 综合评估矩阵药物UC疗效CD疗效安全性指南推荐2025市场综合定位 Infliximab ★★★★ ★★★⚠⚠⚠ UC一线/CD强推 ★★ 经典基石，CD穿透型不可替代 Adalimumab ★★ ★★★★⚠⚠⚠ UC低效/CD强推 ★ CD炎症型首选，UC偏弱 Vedolizumab ★★★★ ★★★✓✓✓✓ UC一线/CD条件性 ★★★★★ 安全性标杆+IBD销冠 Ustekinumab ★★★ ★★★ ⚠ 低-中 UC中效/CD强推 ★★★ 类似药冲击，市场退位 Guselkumab ★★★★ ★★★★★✓ 低 UC高效/CD高效 ★★ CD最强新星，GALAXI胜出 Risankizumab ★★★ ★★★★✓ 低 UC高效/CD高效 ★★★★★ IBD放量明星，增长引擎 Mirikizumab ★★★ ★★★✓ 低 UC中效/CD中效 ★ 礼来IBD处女作 Tofacitinib ★★★★ —⚠⚠⚠⚠ UC限TNF失败后 ★ 安全标签边缘化 Upadacitinib ★★★★★ ★★★★★⚠⚠⚠⚠ UC限TNF失败/CD低效初治 ★★★ 疗效之王，安全标签限使用 Ozanimod ★★★ — ⚠ 低-中 UC高效/CD未批 ★ UC口服选择 Etrasimod ★★★ — ⚠ 低-中 UC高效/CD未批 ★ UC口服后起之秀 Tulisokibart* ★★★★☆ — 待定待III期待定 TL1A领跑者，默沙东108亿6.2 靶点层面竞争格局① TNF-α抑制剂：黄昏将军开创IBD生物制剂时代，CD穿透型/瘘管型仍重要。但生物类似药冲击+安全性劣势，市场份额持续萎缩。② IL-23抑制剂：新时代主力军从Ustekinumab（p40）到p19选择性抑制剂，正成为IBD中坚力量。p19选择性抑制剂保留IL-12/Th1，安全性更优。Guselkumab在GALAXI头对头胜出。Skyrizi成为艾伯维继Humira后的核心增长引擎。③ 抗整合素：肠道靶向代表+IBD销冠 Vedolizumab是IBD领域销售额第一的药物（2025年~61亿美元，100%来自IBD）。肠道选择性+卓越长期安全性+SC剂型便利性。④ JAK抑制剂：疗效天花板，安全性地板 Upadacitinib展示IBD最强疗效。但FDA标签限制+黑框警告使临床使用受限。在CD中因回肠型不显著有效而初治归为低效，TNF失败后升级高效。⑤ TL1A抑制剂：下一个王炸唯一同时调控炎症与纤维化的靶点。广谱共刺激阻断（Th1+Th17+Th2），II期数据接近JAK水平。若III期延续，有望成为CD纤维化/狭窄型首选。七、结语与关键要点速览 IBD治疗正从"有什么用什么"向"精准选择"转变。Vedolizumab以肠道选择性成为安全性标杆和IBD销冠；IL-23 p19抑制剂兼顾疗效与安全（优于Ustekinumab），是新一代中坚；JAK抑制剂疗效最强但安全标签限使用；TL1A抑制剂同时靶向炎症与纤维化，有望带来下一个范式转变。关键要点速览 UC疗效最强：Upadacitinib（JAK1）诱导缓解25.5%、维持缓解39%，但FDA限TNF失败后使用。 CD疗效并列最强：Guselkumab（IL-23）和Upadacitinib（JAK1）不分伯仲。Guselkumab诱导34%/维持44%，GALAXI头对头优于Stelara。安全性排序：Vedolizumab（最优）> IL-23 p19抑制剂（低风险）> Ustekinumab（低-中，因阻断IL-12导致恶性肿瘤/PRES/非感染性肺炎警告）> S1P（低-中）> TNF-α（高）> JAK（最高）。 IL-23 p19优于Ustekinumab：p19选择性保留IL-12/Th1保护性免疫，无恶性肿瘤、PRES、非感染性肺炎警告（处方信息5条 vs Ustekinumab 9条）。IL-23 p19的肝毒性可监测可控。 UC一线高效：Infliximab、Vedolizumab、Ozanimod、Etrasimod、Risankizumab、Guselkumab。JAK限TNF失败后。Adalimumab在UC归为低效。 CD指南：初治高效=TNF-α+IL-23+Vedolizumab；Upadacitinib初治CD归低效（回肠型不显著），TNF失败后升级高效。Vedolizumab在CD仅条件性推荐。 IBD销冠：Vedolizumab（2025年~61亿，100% IBD，SC剂型驱动增长）。排序：Vedolizumab > Risankizumab（~56亿）> Ustekinumab（~46亿，类似药暴跌）。 TL1A：下一个王炸。同时调控炎症+纤维化，广谱共刺激阻断，II期疗效接近JAK。默沙东108亿+罗氏71亿重注。主要参考文献 FDA Prescribing Information: Infliximab, Adalimumab, Vedolizumab, Ustekinumab, Guselkumab, Risankizumab, Mirikizumab, Tofacitinib, Upadacitinib, Ozanimod, Etrasimod AGA Clinical Practice Guideline on Moderate-to-Severe UC (Gastroenterology, 2024;167(7):1307-1343) AGA Living Clinical Practice Guideline on Moderate-to-Severe CD (Gastroenterology, 2025;169(7):1397-1448) 中国溃疡性结肠炎诊治指南（2023年·西安） STRIDE-II共识 (2021) 各药物III期注册临床试验 Bamias G, et al. Targeting TL1A and DR3. Gut, 2024 Tulisokibart ARTEMIS-UC Phase 2 (NEJM) 各公司2021-2025年年报（艾伯维、强生、武田、辉瑞、礼来、BMS）

2026-08-06

·PRNewswire

cAMPfield Strengthens Leadership Team with Key Executive Appointments, Including Graham Heap, MD, PhD as President, R&D, to Advance Prifemilast into Global Phase 2 Development for Inflammatory Bowel Disease

Graham Heap, MD, PhD, formerly Vice President and Program Leader for Takeda's global TYK2 immunology franchise, appointed President, Research and Development Also appointed: Ezequiel Neimark, MD, Head of Clinical Development; Taylor Spector, PhD, Head of Medical Affairs; Scott Stirn, DSc, Head of CMC cAMPfield Therapeutics is advancing prifemilast, a once-daily oral PDE4 inhibitor, for the treatment of inflammatory bowel disease (IBD) into global Phase 2 trials in moderate-to-severe ulcerative colitis and Crohn's disease SAN DIEGO, Aug. 3, 2026 /PRNewswire/ -- cAMPfield Therapeutics, Inc. (cAMPfield), a clinical-stage biopharmaceutical company formed to develop well-tolerated and highly effective oral medicines for immune-mediated inflammatory diseases, today announced key executive appointments to its senior leadership team. Continue Reading Graham Heap Graham Heap, MD, PhD joins as President, Research and Development (R&D), with responsibility for leading all the Company's research and development activities. Ezequiel Neimark, MD joins as Head of Clinical Development and will lead clinical execution for the prifemilast program in ulcerative colitis (UC) and Crohn's disease (CD). Taylor Spector, PhD joins as Head of Medical Affairs and will lead medical strategy, evidence generation, scientific communications, and external engagement. Scott Stirn, DSc joins as Head of Chemistry, Manufacturing, and Controls (CMC) and will lead drug substance and drug product development, manufacturing scale-up, analytical development, and clinical supply of prifemilast. These appointments deepen cAMPfield's leadership bench as the company advances prifemilast, a potentially best-in-class once-daily oral PDE4 inhibitor, into global Phase 2 trials in moderate-to-severe UC and CD. "Building a world-class leadership team with a proven track record of developing therapies for immune-mediated diseases is critical to our success," said Bill Gerhart, Chief Executive Officer of cAMPfield. "Graham, Ezequiel, Taylor, and Scott each bring deep expertise in inflammatory disease drug development and share our passionate belief that patients with IBD need better oral treatment options. Their considerable experience and leadership will be instrumental as we advance prifemilast through global Phase 2 development and position cAMPfield as a leader in IBD." "The treatment landscape for IBD continues to evolve, yet many patients still do not achieve durable disease control with existing therapies," said Dr. Heap. "I've long believed the potential of the PDE4 pathway has been underappreciated in IBD. Prifemilast combines a differentiated mechanism with encouraging clinical data, and I believe it can become an important new oral treatment option for patients with IBD. I look forward to working with the team to advance its development and to help build a broader pipeline beyond it." In addition to these appointments, cAMPfield's leadership team includes other accomplished executives building the company's technical, operational, clinical, and regulatory foundation. Patricia Turney, MBA, Chief Technical Officer, leads technical operations and manufacturing, bringing prior experience from Acelyrin, Arcutis, and Amgen. John Kempen, MS, Senior Vice President of Clinical Development Operations, oversees clinical execution for the prifemilast program, drawing on prior experience from Gossamer Bio, Receptos/Celgene, Ardea Biosciences/AstraZeneca, Allergan, PPD, and ICON. Rita Shah, PharmD, Vice President of Regulatory Affairs, directs the company's global regulatory strategy, leveraging prior experience from Vertex Pharmaceuticals, MBX Biosciences, AstraZeneca, and Johnson & Johnson. Biographies Graham Heap, MD, PhD – President, R&D A physician-scientist with an academic foundation in IBD and extensive development experience across gastroenterology, dermatology and rheumatology, Dr. Heap brings broad leadership expertise advancing therapies for immune-mediated diseases. Most recently, he served as Vice President and Program Leader for Takeda's global TYK2 immunology franchise, leading a large global cross-functional organization responsible for the strategy and execution of a late-stage development portfolio spanning six immune-mediated disease indications. He led zasocitinib from program integration through Phase 2 and Phase 3 readouts, including head-to-head trials against multiple comparators, while expanding the portfolio into five additional indications in Phase 2 or Phase 3 development. Prior to Takeda, Dr. Heap advanced multiple immunology and UC development programs at AbbVie, including risankizumab and ravagalimab. He earned his MBBS from St. George's, University of London and his PhD from Barts and The London School of Medicine and Dentistry. Ezequiel Neimark, MD – Vice President, Head of Clinical Development During more than a decade at AbbVie, Dr. Neimark held senior development leadership roles across gastroenterology, dermatology, and rheumatology and contributed to multiple pivotal IBD programs with adalimumab and risankizumab. He most recently served as Head of Asset/Indication for Skyrizi®, Humira®, ABBV-547, and ABBV-423, and is a physician-scientist trained in gastroenterology and hepatology. Taylor Spector, PhD – Executive Director, Head of Medical Affairs Dr. Spector brings nearly 15 years of Medical Affairs experience across all stages of the product lifecycle advancing programs in immune-mediated inflammatory diseases. Most recently she served as Global Medical Lead for Takeda's TYK2 program in Dermatology. Previously, she held Medical Affairs and Commercial leadership roles at Sobi, Alexion Pharmaceuticals, Sage Therapeutics, Amarin, and AstraZeneca. Scott Stirn, DSc – Executive Director, Head of CMC Dr. Stirn brings over two decades of experience advancing the product development and manufacturing of small molecules, peptides, and biologics from discovery through clinical development. Most recently, as Director and Head of Early Phase Product Development at Neurocrine Biosciences, he served as a global program and CMC lead across multiple small-molecule, peptide, and gene therapy programs, and contributed to the CMC regulatory filings supporting approved therapies including Ingrezza® (valbenazine) and Crenessity® (crinecerfont). Earlier in his career, he led formulation and product development efforts at Pharmatek, Celgene, and Arena Pharmaceuticals, spanning oral and injectable programs—including the development of lorcaserin (Belviq®) and S1P receptor modulator assets. About Inflammatory Bowel Disease Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is a chronic immune-mediated inflammatory disease that affects more than 2.4 million people in the United States and remains an area of substantial unmet medical need. Despite significant advances in treatment, many patients fail to achieve durable remission or lose response over time, resulting in frequent treatment switching. While biologic therapies have transformed outcomes for many patients, there remains a need for additional effective, well-tolerated treatment options. Convenient oral therapies are an important part of the treatment landscape, yet currently approved oral agents for IBD are limited by tolerability, safety concerns and/or modest efficacy. About Prifemilast Prifemilast is an investigational, once-daily, PDE4B-selective inhibitor that has been studied in more than 700 participants to date, including more than 250 participants treated for up to 52 weeks. Prifemilast preferentially inhibits PDE4B, the isoform most closely associated with anti-inflammatory activity, while minimizing inhibition of PDE4D, an isoform associated with dose-limiting adverse effects. Across clinical studies, prifemilast has been well tolerated, with treatment discontinuation rates comparable to placebo, and with demonstrated efficacy thus far in Phase 3 clinical trials in plaque psoriasis. About cAMPfield Therapeutics cAMPfield Therapeutics is a clinical-stage biopharmaceutical company focused on developing well-tolerated and highly effective oral medicines for immune-mediated inflammatory diseases, including inflammatory bowel disease. cAMPfield was founded by Mountainfield Venture Partners in partnership with executives who played key roles in the development and/or commercialization of Entyvio®, Humira®, Otezla®, and Zeposia®. cAMPfield holds exclusive global development and commercialization rights to prifemilast outside Greater China through a license agreement with Newsoara Biopharma Co., Ltd. The company is headquartered in San Diego, California. For more information, visit . Media and Investor Contact Rayne Rodgers [email protected] cAMPfield Therapeutics All third-party product names, company names, and logos are trademarks™ or registered® trademarks of their respective holders. Use of them does not imply any affiliation with or endorsement by them. 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临床3期临床2期高管变更引进/卖出

2026-08-06

·消小募

用了“乌司奴”还是复发了？你不是一个人！溃结换药到底怎么选？

需要的朋友可以点击蓝字链接~病友交流群-临床招募资讯、入组申请！一、这种病，比你想象的更常见溃疡性结肠炎（UC）绝不是什么“罕见病”。《柳叶刀》2023年综述显示，全球约有500万人正在与它共处，北美和欧洲炎症性肠病（IBD）的患病率已稳定在0.5%–1.0%，其中溃疡性结肠炎约占IBD的40%–50%。而在中国，这个数字正在以惊人的速度攀升——2019年中国IBD患病人数约为40万（UC约占其中2/3），预计到2030年将突破100万。它被称为“绿色癌症”：不直接致命，却足够顽固，足够磨人。 2020年8月28日，日本时任首相安倍晋三因溃疡性结肠炎复发宣布辞职。这让我们不得不正视一个问题：如果连首相级别能用到的医疗资源都试过了还是会复发，普通患者还能怎么办？这就是溃疡性结肠炎最残酷的真相——它不是靠“找到一种有效药”就能一劳永逸解决的病。随着时间推移，药物可能一个个失效，这个过程在医学上叫“继发性失应答”。三、为什么生物制剂会“失效”？当现有通路都被堵住，还能从哪里突破？抗TNF、抗整合素、抗IL-12/23、JAK抑制剂——你有没有发现，这些药物虽然靶点不同，但有一个共同点：它们都瞄准的是“适应性免疫通路”（T细胞、B细胞、炎症因子）或者淋巴细胞迁移。但肠道里还有另一套炎症放大系统，长期被忽视了——肥大细胞。肥大细胞是肠道黏膜里的“哨兵”。在UC患者的炎症肠段中，它们大量聚集并持续脱颗粒，释放组胺、类胰蛋白酶等炎症介质。更关键的是，它们通过一个叫“MRGPRX2”的受体，形成了一个“炎症正反馈环路”：MRGPRX2被激活→肥大细胞脱颗粒→释放CPA3→ADM经CPA3切割后产生PAMP-12→PAMP-12再结合MRGPRX2→更多肥大细胞脱颗粒。这就好比一根火柴点燃了一堆干柴，干柴又点燃了更多火柴。《胃肠病学》（Gastroenterology）2021年发表的研究发现，携带MRGPRX2保护性等位基因Asn62Ser变异的人群，UC发病风险明显较低——因为这个变异让MRGPRX2的激活效率降低了。反过来证明，如果能用一种药物阻断MRGPRX2，理论上就能掐断这个恶性循环，让反复发作的炎症停下来。目前，一款针对MRGPRX2靶点的在研药物正在国内开展临床研究，入组条件为：既往使用过至少一种常规治疗（如5-ASA、激素或免疫调节剂）或生物制剂（抗TNF-α、抗α4β7整合素、抗IL-12/23抗体）回到最初那个问题——“已经用到顶级药了还是复发，是不是没救了？” 看完这篇文章你应该知道，不是没救了，而是需要换一个逻辑。继发性失应答不是治疗的终点，而是一个转折点——它告诉你，是时候重新评估疾病通路、药物浓度和换药策略了。 UC的治疗，正在从“有什么药用”进入“该怎么选”的精准时代。当适应性免疫的通路一个个被堵住，肥大细胞-MRGPRX2这条先天免疫通路或许正是下一个突破口。【免责声明】本文仅供医学科普参考，不构成诊疗建议。具体用药方案请遵医嘱，切勿自行调整。参考文献： [1] Lancet. Ulcerative colitis. *Lancet*. 2023;402(10401):571-584. doi:10.1016/S0140-6736(23)00966-2 [2] 钟捷，等。全球炎症性肠病的流行趋势分析及诊治现状。 *诊断学理论与实践*. 2025. doi:10.16150/j.1671-2870.2025.04.003 [3] 《人民日报》健康时报。日本首相安倍晋三因溃疡性结肠炎辞职，这病被称为“绿色癌症”. 2020-09-01. [4] 腾讯新闻。安倍辞职真相：溃疡性结肠炎折磨他50年，曾接受血液净化治疗。 2020-08-29. [5] 南方plus. 安倍晋三溃疡性结肠炎复发辞职，粪菌移植疗法曾传闻与其相关。 2020-08-27. [6] Savelkoul EHJ, et al. Systematic Review and Meta-analysis: Loss of Response and Need for Dose Escalation of Infliximab and Adalimumab in Ulcerative Colitis. *Inflamm Bowel Dis*. 2023;29(3):429-438. doi:10.1093/ibd/izac189 [7] Feuerstein JD, et al. AGA Clinical Practice Guidelines on the Management of Moderate to Severe Ulcerative Colitis. *Gastroenterology*. 2020;158(5):1450-1461. doi:10.1053/j.gastro.2020.01.006 [8] Danese S, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. *Lancet*. 2022;399(10341):2113-2128. doi:10.1016/S0140-6736(22)00566-6 [9] Friedberg S, et al. Upadacitinib is effective and safe in both ulcerative colitis and Crohn's disease: prospective real-world experience. *Clin Gastroenterol Hepatol*. 2023;21(7):1913-1923. doi:10.1016/j.cgh.2022.09.020 [10] 艾伯维中国。瑞福®（乌帕替尼缓释片）第四个适应症在华获批，用于治疗中重度活动性溃疡性结肠炎。 2023-02-20. [11] 中国国家药品监督管理局。艾曲莫德（Etrasimod）获批上市信息。 2026-02. [12] Chen E, et al. Inflamed ulcerative colitis regions associated to MRGPRX2-mediated mast cell degranulation and cell activation modules, defining a new therapeutic target. *Gastroenterology*.2021;160(5):1709-1724. doi:10.1053/j.gastro.2020.12.076 [13] Vande Casteele N, et al. Trough concentrations of infliximab guide dosing for patients with inflammatory bowel disease. *Gastroenterology*. 2015;148(7):1320-1329. doi:10.1053/j.gastro.2015.02.031 [14] Papamichael K, et al. Infliximab concentration-based dosing is superior to clinically based dosing during maintenance therapy in Crohn's disease: TAILORIX post hoc analysis. *Inflamm Bowel Dis*. 2020;26(6):845-851. doi:10.1093/ibd/izz191 [15] Vande Casteele N, et al. Aiming for therapeutic concentrations: TAXIT study results. *United European Gastroenterol J*. 2014;2(Suppl 1):Abstract OP023. [16] 中华医学会消化病学分会炎症性肠病学组。中国溃疡性结肠炎诊治指南（2023年·西安）。 *中华消化杂志*. 2024;44(2):73-99. [17] Rubin DT, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment. *J Crohns Colitis*. 2022;16(2):179-194. doi:10.1093/ecco-jcc/jjab178 [18] Sandborn WJ, et al. Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis. *N Engl J Med*. 2021;385(14):1280-1291. doi:10.1056/NEJMoa2033617 点击阅读原文了解更多

100 项与盐酸奥扎莫德相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10967	盐酸奥扎莫德	L04AA38	DB12612

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
溃疡性结肠炎	美国	Bristol Myers Squibb Co.	2021-05-27
复发性多发性硬化	澳大利亚	Celgene Pty Ltd.	2020-07-17
复发-缓解型多发性硬化	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-05-20
复发-缓解型多发性硬化	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-05-20
复发-缓解型多发性硬化	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-05-20
复发-缓解型多发性硬化	挪威	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性中度溃疡性结肠炎	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性中度溃疡性结肠炎	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性中度溃疡性结肠炎	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性中度溃疡性结肠炎	挪威	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性重度溃疡性结肠炎	欧盟	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性重度溃疡性结肠炎	冰岛	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性重度溃疡性结肠炎	列支敦士登	Bristol-Myers Squibb Pharma EEIG	2020-05-20
活动性重度溃疡性结肠炎	挪威	Bristol-Myers Squibb Pharma EEIG	2020-05-20
多发性硬化症	美国	Bristol Myers Squibb Co.	2020-03-25

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
克罗恩病	申请上市	中国	Bristol Myers Squibb Co.	2021-07-30
小儿克罗恩病	临床3期	美国	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	澳大利亚	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	比利时	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	加拿大	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	法国	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	德国	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	匈牙利	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	波兰	Bristol Myers Squibb Co.	2023-08-22
小儿克罗恩病	临床3期	西班牙	Bristol Myers Squibb Co.	2023-08-22

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


DDW2026	N/A	炎症性肠病	18,494	Vedolizumab	積憲壓獵鑰醖鑰艱鏇獵(蓋鏇齋遞淵簾鬱簾蓋廠) = 範壓艱憲鬱壓鹹顧構襯鏇壓夢簾憲鹹鬱齋鑰餘 (鬱膚觸觸築齋網淵顧範 )	积极	2026-05-02
				Ustekinumab	積憲壓獵鑰醖鑰艱鏇獵(窪積醖鏇窪繭蓋願艱襯) = 廠選觸糧夢築願憲簾製鏇衊膚鑰衊觸鏇廠餘鏇 (鑰膚鹹製積蓋衊鏇齋餘 )
NCT05369832 (CTgov)	临床4期	溃疡性结肠炎	139	Ozanimod (Cohort 1: Ozanimod Advanced Therapy Naïve)	憲顧醖憲觸簾遞憲齋鏇 = 齋艱壓蓋願鹽醖衊範繭鹽廠艱夢觸廠選糧網窪 (鏇築膚築選鬱積膚鑰觸, 醖鏇壓膚醖艱鬱積壓構 ~ 遞糧窪蓋淵齋範顧繭鹹) 更多	-	2026-02-10
				Ozanimod (Cohort 2: Ozanimod Advanced Therapy Exposed)	夢蓋淵齋遞蓋鏇鹽餘鬱 = 齋繭鹽簾壓憲壓憲衊繭艱淵鏇築夢襯製蓋膚餘 (淵遞選艱築繭衊壓糧衊, 範鹹餘鏇選築餘網廠窪 ~ 觸顧艱範範壓壓繭製衊) 更多
NCT04140305 (ENLIGHTEN, ACTRIMS2026)	临床3期	复发性多发性硬化	188	Ozanimod 0.92 mg	憲餘醖膚積壓構衊蓋積(製顧憲簾鹽遞構製淵淵) = 醖餘餘製網膚遞顧築艱鹽膚簾餘獵獵選顧鑰壓 (艱範鬱襯鬱範鏇糧遞夢 ) 更多	积极	2026-02-05
NCT04140305 (ENLIGHTEN, ACTRIMS2026)	临床3期	复发性多发性硬化 Neurofilament light chain (NfL)	157	Ozanimod 0.92 mg (early relapsing multiple sclerosis)	鹹壓廠鹹觸齋廠夢築夢(鏇衊觸淵範膚簾鏇艱夢) = 淵憲憲襯夢蓋壓築衊製窪網顧簾憲積窪製壓繭 (選獵願齋獵築鏇醖鹹範 ) 更多	积极	2026-02-05
ACTRIMS2026	N/A	复发性多发性硬化	85	Ozanimod	糧憲鏇艱蓋醖艱廠夢鑰(鹽積衊鏇遞廠鹹鏇獵衊) = 糧廠願構簾鑰積壓齋選齋範繭顧蓋壓觸憲夢鹹 (構糧鹽鑰鏇窪鏇鑰網醖 ) 更多	积极	2026-02-05
COAST (ACTRIMS2026)	N/A	多发性硬化症	23	Ozanimod	築淵範獵醖蓋醖獵願鬱(襯鏇鏇鹹觸範蓋鏇壓餘) = 憲廠夢襯鬱選艱網襯鑰觸淵窪築夢鹹選鹹餘壓 (淵鬱壓觸淵鹹願觸餘淵 ) 更多	积极	2026-02-05
NCT02531126 (True North \| True North and Open-Label Extension Analyses, CTgov)	临床3期	溃疡性结肠炎	877	Placebo (RPC01-3101 Placebo-Placebo)	鹹憲鹽餘構淵壓蓋製餘 = 製齋遞糧憲積鏇蓋廠壓構醖夢憲鑰鹹遞築築鏇 (製範鬱夢鑰廠夢糧鏇鬱, 鏇範選範製壓廠構襯餘 ~ 醖憲壓膚觸蓋鏇夢糧顧) 更多	-	2025-12-31
				Placebo+Ozanimod (RPC01-3101 Ozanimod-Placebo)	鹹憲鹽餘構淵壓蓋製餘 = 鹽醖築襯艱顧鑰鹽繭憲構醖夢憲鑰鹹遞築築鏇 (製範鬱夢鑰廠夢糧鏇鬱, 鏇顧鬱網壓積鬱鬱糧獵 ~ 蓋範糧憲壓襯選簾鹽齋) 更多
NCT03440372 (CTgov)	临床3期	克罗恩病	625	ozanimod (Treatment 1)	鏇窪窪夢網獵糧膚膚餘 = 夢襯艱範衊願艱鬱蓋繭窪窪鹹衊鏇願齋鹹夢窪 (積觸蓋夢醖鑰餘製齋蓋, 積範鏇築積襯衊蓋餘製 ~ 鏇築積糧鑰鏇鏇襯膚鹽) 更多	-	2025-11-04
				placebo+ozanimod (Treatment 2)	鏇窪窪夢網獵糧膚膚餘 = 襯艱獵淵觸憲餘醖製鹽窪窪鹹衊鏇願齋鹹夢窪 (積觸蓋夢醖鑰餘製齋蓋, 觸網膚醖膚簾艱觸製衊 ~ 鹹衊膚廠齋窪淵鑰壓觸) 更多
NCT02576717 (DAYBREAK, Pubmed \| Mult Scler)	临床3期	复发性多发性硬化	2,494	Ozanimod 0.92 mg/d	獵鬱範鹽糧窪鑰壓淵窪(願壓鹽窪廠蓋蓋鑰積齋) = 廠膚遞窪網繭壓壓範顧顧餘願範繭鹽夢醖築餘 (網選選製鏇範淵艱蓋餘, 0.082 ~ 0.117) 更多	积极	2025-11-01
NCT03464097 (CTgov)	临床3期	克罗恩病	550	Ozanimod (Ozanimod 0.92 mg / Ozanimod 0.92 mg)	襯醖積鬱簾鬱膚餘繭窪 = 膚蓋範淵艱餘壓壓淵襯醖壓廠鏇艱顧觸醖壓憲 (鏇窪衊選窪窪顧繭願鏇, 鹽齋鑰鑰衊艱夢窪簾簾 ~ 繭夢蓋選構願廠網鑰鏇) 更多	-	2025-10-09
				Ozanimod (Ozanimod 0.92 mg / Placebo)	襯醖積鬱簾鬱膚餘繭窪 = 餘壓選積選鹹觸鬱簾顧醖壓廠鏇艱顧觸醖壓憲 (鏇窪衊選窪窪顧繭願鏇, 醖構艱鏇醖鑰範遞選艱 ~ 憲齋窪淵醖網選鹽鏇夢) 更多