To evaluate the efficacy of fontolizumab in subjects with active rheumatoid arthritis as determined by a 50% improvement of an American College of Rheumatology criteria (ACR50) response at Week 14 (Stage A of study).

开始日期2005-12-01

申办/合作机构

PDL BioPharma, Inc.

NCT00072943

/ Completed临床2期

A Phase II, Double-Blind, Placebo-Controlled Study to Determine the Safety and Efficacy of a Humanized Anti-Interferon-γ Monoclonal Antibody (HuZAF) Administered to Patients With Moderate to Severe Crohn's Disease

The purpose of the HARMONY study is to assess the safety and efficacy of an investigational drug called HuZAF, in patients with moderate to severe Crohn's disease (CD). HuZAF is a humanized anti-Interferon-gamma (anti-IFN-γ) monoclonal antibody, which binds and blocks IFN-γ, a protein in the immune system that is involved in inflammation. Antibodies are proteins normally produced by our immune system to help fight off foreign substances. Scientists have been able to make therapeutic humanized monoclonal antibodies, similar to the antibodies in our bodies, to target diseases.

开始日期2002-03-01

申办/合作机构

Abbott Biotherapeutics Corp.

100 项与芳妥珠单抗相关的临床结果

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100 项与芳妥珠单抗相关的转化医学

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100 项与芳妥珠单抗相关的专利（医药）

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项与芳妥珠单抗相关的文献（医药）

2025-12-05·Hematology-American Society of Hematology Education Program

Hemophagocytic lymphohistiocytosis: do we have a solution for TMI (too much inflammation)?

Review

作者: La Rosée, Paul ; Machowicz, Rafal

Abstract:

Hemophagocytic lymphohistiocytosis (HLH) and the related HLH-spectrum disorders macrophage activation syndrome, macrophage activation-like syndrome, and treatment-associated immune-effector-cell–associated HLH-like syndrome are extreme forms of too much inflammation (TMI). Adult patients with HLH associated with hematologic malignancies have a 70% to 80% mortality rate due to delayed diagnosis, prolonged immunosuppression with associated secondary infections, and disease recurrence. In recent years, educational efforts and epidemiological evolution have increased diagnostic awareness. This has been catalyzed by the COVID-19 pandemic, the first approved anti-interferon gamma antibody for primary relapsed/refractory HLH, advancements in the treatment of posttransplant graft-versus-host disease, and the broad availability of T-cell–engaging therapeutics. These truly challenging-to-diagnose entities under the cytokine storm umbrella confer TMI, causing multiorgan dysfunction and early death. Novel prognostic models, differential diagnosis with the help of advanced diagnostic algorithms, preemptive therapeutic interventions, and more individualized cytokine-directed treatment options have moved this previously neglected area in adult hematology to the forefront of the hematologist's daily practice.

2025-09-01·PHARMACOTHERAPY

Biological Therapy and Small Molecules for Adults With Crohn's Disease: Systematic Review and Network Meta‐Analysis

Review

作者: Gorski, Daniela ; Pontarolo, Roberto ; Tonin, Fernanda Stumpf ; Lazo, Raul Edison Luna ; de Souza, Dalton de Assis ; Borba, Helena Hiemisch Lobo

ABSTRACT:

First‐line therapeutic approaches for Crohn's disease include immunosuppressants, aminosalicylates, and corticosteroids. However, more than one‐third of patients are resistant to these treatments and require second‐line therapies. Our goal was to synthesize the evidence on the efficacy and safety of biologics and small molecules for inducing remission in patients with moderate‐to‐severe Crohn's disease. A systematic review was conducted by searching for randomized controlled trials on the target population in PubMed, Scopus, and Web of Science (March 2025). Data synthesis for the outcomes of remission, health‐related quality of life (HRQoL), and safety was performed using network meta‐analyses and surface under the cumulative rating curve (SUCRA) analyses. The results were presented as risk ratios with 95% credible intervals. We included 55 trials ( n = 16,113 patients) evaluating 26 biological drugs across 83 doses and six small molecules across 15 doses. Similar results were obtained in the sensitivity analyses conducted across different measurement time points. Alongside infliximab 5 mg/kg (SUCRA 98.6%), 10 mg/kg (92%), and 20 mg/kg intravenous (91.8%), the recently approved drugs guselkumab 1200 mg (83.2%), 600 mg (89.2%), and 200 mg intravenous (90.1%), as well as mirikizumab 600 mg (91.5%) and 1000 mg intravenous (82.4%) presented higher probabilities of disease remission and were associated with increased HRQoL. Drugs such as certolizumab, andecaliximab, fontolizumab, abatacept, and etanercept ranked low for remission (SUCRA < 40%) and presented high probabilities of serious adverse events (over 60%). Small molecules presented an intermediate profile. Inhibitors of interleukin‐23 appear to be promising alternatives for the treatment of moderate‐to‐severe Crohn's disease. Given their safety profile, some anti‐TNF drugs should be avoided in practice. Trial Registration: PROSPERO: CRD42024519150

2024-06-01·Rheumatology and therapy

Population Pharmacokinetics of the Anti-Interferon-Gamma Monoclonal Antibody Emapalumab: An Updated Analysis

Article

作者: Laveille, Christian ; Brossard, Patrick

INTRODUCTION:

Emapalumab is a fully human monoclonal antibody that targets free and receptor-bound interferon-gamma (IFNγ), neutralizing its biological activity. IFNγ levels differ by orders of magnitude between patients with primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS; a form of secondary HLH) in systemic juvenile idiopathic arthritis (sJIA). Therefore, this study aimed to develop a population pharmacokinetic model for emapalumab across a patient population with a wide range of total (free and emapalumab-bound) IFNγ levels using observations from patients with primary HLH or MAS in sJIA in clinical trials.

METHODS:

Pharmacokinetic data were pooled (n = 58; 2709 observations) from studies enrolling patients administered emapalumab for primary HLH or MAS in sJIA. Patients with primary HLH were administered emapalumab 1 mg/kg (potentially increasing to 3, 6, and up to 10 mg/kg based on clinical response) every 3 days. Patients with MAS in sJIA were administered emapalumab 6 mg/kg, followed by 3 mg/kg every 3 days until day 15 and twice weekly until day 28. An earlier population PK model was re-parameterized using this data.

RESULTS:

The final model for emapalumab comprised a 2-compartment model with first-order elimination. Emapalumab clearance remains constant when the total IFNγ concentration (free and emapalumab-bound) is < ~ 10,000 pg/ml but increases proportionally to total IFNγ concentration above this threshold. Emapalumab clearance was estimated to be 0.00218, 0.00308, 0.00623 and 0.01718 l/h at total serum IFNγ concentrations of 10³, 10⁴, 10⁵ and 10⁶ pg/ml, respectively, with corresponding terminal half-lives of 19.2, 13.8, 7.18 and 3.12 days for a 1-year-old patient weighing 10 kg with primary HLH. The median terminal half-life for emapalumab in patients with MAS in sJIA was estimated to be 24.0 (range, 6.13-32.4) days, which is similar to observations in healthy volunteers.

CONCLUSIONS:

Emapalumab pharmacokinetics in patients with primary HLH and MAS in sJIA were described by a two-compartment model with fixed allometric exponents and an age-related effect. Differences in total IFNγ levels between patients with primary HLH and MAS may affect emapalumab pharmacokinetics, suggesting that each indication may require different dosing to rapidly control hyperinflammation.

TRIAL REGISTRATION:

Clinicaltrials.gov identifiers: NCT01818492, NCT03311854 and NCT02069899.

项与芳妥珠单抗相关的新闻（医药）

2025-09-29

·闲谈 Immunology

10个自免致病细胞因子

自身免疫性疾病的核心病理机制是免疫系统过度激活，致病细胞因子作为免疫细胞间的 “信号分子”，会持续放大炎症反应、破坏自身组织。 Cytokines in pathogenesis of psoriasis，10.1093/intimm/dxv0631. 肿瘤坏死因子 -α（TNF-α）核心关联疾病类风湿关节炎（RA）、强直性脊柱炎（AS）、银屑病（PsO）、银屑病关节炎（PsA）、溃疡性结肠炎（UC）、克罗恩病（CD）致病机制促进巨噬细胞、中性粒细胞等炎症细胞向病变部位浸润；诱导滑膜细胞、成纤维细胞释放蛋白酶，破坏关节软骨和骨组织；激活血管内皮细胞，加重组织水肿和炎症。靶向治疗药物药物名称药物类别靶点特性主要适应症依那西普 TNF 受体融合蛋白竞争性结合 TNF-α/β RA、AS、PsO、PsA 阿达木单抗抗 TNF-α 单克隆抗体（全人源）直接中和 TNF-α 活性 RA、AS、PsO、PsA、UC、CD 英夫利西单抗抗 TNF-α 单克隆抗体（嵌合）直接中和 TNF-α 活性 RA、AS、PsO、PsA、UC、CD 戈利木单抗抗 TNF-α 单克隆抗体（全人源）直接中和 TNF-α 活性 RA、AS、PsA、UC2. 白细胞介素 - 6（IL-6）核心关联疾病 RA、AS、系统性红斑狼疮（SLE）、巨细胞动脉炎（GCA）、Castleman 病致病机制调控 “急性期反应”（如 C 反应蛋白升高、血沉加快）；促进 B 细胞活化分化为浆细胞，产生自身抗体（如抗环瓜氨酸肽抗体）；刺激 T 细胞增殖，加重关节滑膜炎症和血管炎。靶向治疗药物药物名称药物类别靶点特性主要适应症托珠单抗抗 IL-6 受体单克隆抗体（人源化）阻断 IL-6 与受体结合 RA、GCA、SLE（合并肾炎 / 血小板减少）司妥昔单抗抗 IL-6 单克隆抗体（人源化）直接中和 IL-6 活性多中心 Castleman 病、RA（难治性）3. 白细胞介素 - 1（IL-1，含 IL-1α/IL-1β）核心关联疾病痛风性关节炎（急性发作）、幼年特发性关节炎（JIA）、成人 Still 病、强直性脊柱炎致病机制启动早期炎症反应，诱导发热、疼痛和组织损伤；促进滑膜细胞释放前列腺素 E2（PGE2），加重关节疼痛和肿胀；参与痛风石形成（IL-1β 激活中性粒细胞吞噬尿酸盐结晶）。靶向治疗药物药物名称药物类别靶点特性主要适应症阿那白滞素 IL-1 受体拮抗剂（重组人源）阻断 IL-1 与受体结合 RA（对 TNF 拮抗剂无效者）、JIA 卡那单抗抗 IL-1β 单克隆抗体（全人源）直接中和 IL-1β 活性急性痛风性关节炎、成人 Still 病利纳西普 IL-1 受体融合蛋白竞争性结合 IL-1α/β 家族性寒冷型自身炎症综合征4. 白细胞介素 - 17A（IL-17A）核心关联疾病银屑病（PsO）、银屑病关节炎（PsA）、强直性脊柱炎（AS）、化脓性汗腺炎致病机制招募中性粒细胞至皮肤 / 关节病灶，诱导角质形成细胞过度增殖（银屑病皮损）；促进滑膜细胞释放 IL-6、TNF-α，放大关节炎症；参与肌腱端炎（AS 特征性病变）的发生。靶向治疗药物药物名称药物类别靶点特性主要适应症司库奇尤单抗抗 IL-17A 单克隆抗体（全人源）直接中和 IL-17A 活性 PsO、PsA、AS 依奇珠单抗抗 IL-17A 单克隆抗体（人源化）直接中和 IL-17A 活性 PsO、PsA、AS 布罗利尤单抗抗 IL-17 受体 A 单克隆抗体（全人源）阻断 IL-17A/F 与受体结合 PsO、PsA5. 白细胞介素 - 23（IL-23）核心关联疾病银屑病（PsO）、银屑病关节炎（PsA）、克罗恩病（CD）、溃疡性结肠炎（UC）致病机制维持 Th17 细胞（分泌 IL-17 的关键 T 细胞）的存活和功能，间接促进 IL-17 释放；诱导肠道固有层免疫细胞活化，加重肠道黏膜炎症（IBD）；参与银屑病皮损中角质形成细胞的异常增殖。靶向治疗药物药物名称药物类别靶点特性主要适应症古塞奇尤单抗抗 IL-23 p19 单克隆抗体（全人源）阻断 IL-23 活性（不影响 IL-12） PsO、PsA、CD 乌司奴单抗抗 IL-12/23 p40 单克隆抗体（全人源）同时阻断 IL-12 和 IL-23 PsO、PsA、CD、UC Risankizumab 抗 IL-23 p19 单克隆抗体（全人源）阻断 IL-23 活性 PsO、PsA、CD、UC6. 转化生长因子 -β（TGF-β）核心关联疾病系统性硬化症（SSc）、类风湿关节炎（RA，晚期纤维化）、特发性肺纤维化（IPF，自身免疫相关）致病机制过度激活成纤维细胞，促进胶原蛋白合成，导致皮肤 / 肺脏纤维化（SSc 特征）；调控免疫细胞分化，失衡时加重自身免疫反应和组织修复异常。靶向治疗药物药物名称药物类别靶点特性主要适应症 Fresolimumab 抗 TGF-β 单克隆抗体（全人源）直接中和 TGF-β1/2/3 活性系统性硬化症（临床阶段）、IPF Galunisertib TGF-β 受体 I 激酶抑制剂阻断 TGF-β 信号通路肝癌（合并自身免疫相关纤维化，临床阶段）7. 白细胞介素 - 36（IL-36，含 IL-36α/β/γ）核心关联疾病泛发性脓疱型银屑病（GPP）、斑块型银屑病（PsO）、掌跖脓疱病致病机制激活角质形成细胞和巨噬细胞，释放促炎因子（如 IL-8），诱发脓疱形成；放大皮肤局部炎症反应，加重银屑病皮损。靶向治疗药物药物名称药物类别靶点特性主要适应症 Spesolimab 抗 IL-36 受体单克隆抗体（全人源）阻断 IL-36 与受体结合泛发性脓疱型银屑病（GPP）、PsO8. 白细胞介素 - 21（IL-21）核心关联疾病系统性红斑狼疮（SLE）、类风湿关节炎（RA）、干燥综合征（pSS）致病机制促进 B 细胞活化、分化为浆细胞，产生抗核抗体（ANA）、抗双链 DNA 抗体（dsDNA）等自身抗体（SLE 核心病理）；激活 Tfh 细胞（滤泡辅助 T 细胞），加重体液免疫紊乱。靶向治疗药物药物名称药物类别靶点特性主要适应症 Blisibimod IL-21 受体融合蛋白竞争性结合 IL-21 SLE（临床阶段，针对肾炎）、RA Mimfilia（Anifrolumab）抗 I 型干扰素受体抗体（全人源）间接抑制 IL-21 下游信号（SLE 中 I 型干扰素与 IL-21 协同作用） SLE（获批）9. 干扰素 -γ（IFN-γ）核心关联疾病多发性硬化症（MS）、系统性红斑狼疮（SLE）、结节病致病机制激活巨噬细胞，释放促炎因子（如 TNF-α、IL-1），加重中枢神经系统炎症（MS 脱髓鞘病变）；调控 T 细胞分化为 Th1 细胞，失衡时诱发自身免疫攻击。靶向治疗药物药物名称药物类别靶点特性主要适应症 Fontolizumab 抗 IFN-γ 单克隆抗体（人源化）直接中和 IFN-γ 活性结节病（临床阶段）、MS（临床阶段） Natalizumab 抗 α4 整合素抗体间接抑制 IFN-γ 介导的 T 细胞迁移 MS、CD（减少炎症细胞浸润）10. 趋化因子 CCL2（MCP-1，单核细胞趋化蛋白 - 1）核心关联疾病类风湿关节炎（RA）、系统性硬化症（SSc）、糖尿病肾病（自身免疫相关）致病机制特异性招募单核细胞、巨噬细胞至关节滑膜或肾脏，分化为破骨细胞（RA 骨破坏）或促进纤维化（SSc / 肾病）；加重局部炎症细胞聚集，放大组织损伤。靶向治疗药物药物名称药物类别靶点特性主要适应症 Carmustine CCL2 受体（CCR2）拮抗剂阻断 CCL2-CCR2 信号通路 RA（临床阶段）、糖尿病肾病（临床阶段） BMS-813160 CCR2 拮抗剂阻断单核细胞迁移 RA（临床阶段）参考资料 Yuping Lai and Chen Dong，Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases，International Immunology, Vol. 28, No. 4, pp. 181–188 doi:10.1093/intimm/dxv063 Type I Interferons in Autoimmunity，J Invest Dermatol. 2022 Mar;142(3 Pt B):793-803. doi: 10.1016/j.jid.2021.11.031. Grebenciucova E and VanHaerents S (2023) Interleukin 6: at the interface of human health and disease. Front. Immunol. 14:1255533. doi: 10.3389/fimmu.2023.1255533

免疫疗法

100 项与芳妥珠单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D04242	芳妥珠单抗	-	DB05111

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
类风湿关节炎	临床2期	美国	PDL BioPharma, Inc.	2005-12-01
结肠炎	临床2期	美国	Abbott Biotherapeutics Corp.	2002-03-01
结肠炎	临床2期	加拿大	Abbott Biotherapeutics Corp.	2002-03-01
克罗恩病	临床2期	美国	Abbott Biotherapeutics Corp.	2002-03-01
克罗恩病	临床2期	加拿大	Abbott Biotherapeutics Corp.	2002-03-01
银屑病	临床2期	-	Biogen (Denmark) A/S	-
银屑病	临床2期	-	PDL BioPharma, Inc.	-