With a prevalence of 2-4% in western countries, Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) is of major concern regarding its substantial impact on the social and physical quality of life. So far, endoscopic sinus surgery remains the treatment of choice when the first line of medical treatment with corticosteroid has failed.
During the last 15 years, several studies have shown that CRSwNP is associated with a T helper 2 (T2) immune response leading to B cell release of IgE, mucosal recruitment of eosinophils from bone marrow via Interleukin (IL)-5, IL-4 and IL-13 mediated chemoattractant production.
New biologic agents capable of blocking T2 cytokines have been developed in the field of eosinophil-associated diseases, shifting the paradigm of treatment for patients with CRSwNP. In the near future, endotype profiling with accurate biomarkers will be mandatory to tailor the treatment of nasal polyposis with specific biologic therapies.
Herein the investigators propose a prospective study monitoring medical records of CRSwNP patients who undergo biologic treatments. The objectives are to assess treatment efficacy on quality of life, to report clinical and biological criteria for prescription and to measure tolerance and compliance.Patient-reported outcomes will be addressed according to their initial clinical profile (allergy, asthma, NSAID, gastroesophageal reflux disease, obstructive apnea, otologic disorder, smoke habit).

开始日期2024-09-02

申办/合作机构-

NCT06572267 / Recruiting临床2期IIT

Safety and Efficacy of Meplazumab in Patients With Coronary Artery Disease: a Single-center, Triple-blinded, Placebo-controlled, Exploratory, Phase 2, Pilot Trial

The development of coronary atherosclerosis is closely related to inflammation, and CD147 may play an important role in its process. The present study was designed to evaluate the effects of long-term administration of mepolizumab (humanized anti-CD147 antibody) on lipid deposition and inflammation in coronary atherosclerotic plaques in patients with high-risk coronary artery disease, and to preliminarily explore the efficacy, safety, and dosage of long-term administration of mepolizumab in this population.

开始日期2024-08-26

申办/合作机构

西京医院第四军医大学

CTIS2023-508069-34-01 / RecruitingIIT

Biomarkers for the prediction of individual CRSwNP patients' responses to mepolizumab

开始日期2024-08-12

申办/合作机构-

100 项与 IL-5 相关的临床结果

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100 项与 IL-5 相关的转化医学

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0 项与 IL-5 相关的专利（医药）

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17,874

项与 IL-5 相关的文献（医药）

2025-01-01·JOINT BONE SPINE

Update on targeted treatments for ANCA-associated vasculitis

Article

作者: Puéchal, Xavier

Targeted therapy has revolutionized the management of ANCA-associated vasculitis (AAV) over the last fifteen years. Rituximab, an approved induction and maintenance agent for severe AAV, is no less effective than cyclophosphamide as induction therapy and particularly useful in relapsing or refractory disease, or in women. In patients with relapsing AAV, granulomatosis with polyangiitis or PR3-ANCA, it is more effective than cyclophosphamide. Rituximab maintenance is superior to the conventional immunosuppressive drugs that it replaces. Low-dose preemptive rituximab infusions are recommended every 6months for 18months, followed by re-evaluation to decide whether 4 additional biannual infusions should be administered, balancing the probability of relapse and the risk of serious infections on rituximab. A growing body of experimental and clinical data shows that C5a pathway inhibition is a promising therapeutic option for AAV, which could reduce glucocorticoids needs. Avacopan is a first approved oral C5A receptor antagonist, used when there is a high risk that glucocorticoids will cause serious adverse events. In eosinophilic granulomatosis with polyangiitis, the importance of IL-5 for eosinophil activation and survival led to evaluation and approval of mepolizumab, a humanized monoclonal antibody directed against IL-5. Mepolizumab showed a steroid-sparing effect. Its effectiveness in active vasculitis remains uncertain and is currently being evaluated. Benralizumab targeting the IL-5 receptor was recently shown to be noninferior to mepolizumab. Rituximab has had disappointing results in non-severe active vasculitis and is being evaluated as maintenance therapy. Plasma exchange is not indicated as first-line treatment but remains recommended when creatinine levels exceed 300μmol/L.

2024-12-31·Gut microbes

Gut microbiota-palmitoleic acid-interleukin-5 axis orchestrates benzene-induced hematopoietic toxicity

Article

作者: Wang, Jingyu ; Gao, Ai ; Han, Lin ; Zhang, Wei ; Jing, Jiaru ; Zhang, Lei ; Kang, Huiwen ; Liu, Ziyan

Due to the annual increase in its production and consumption in occupational environments, the adverse blood outcomes caused by benzene are of concern. However, the mechanism of benzene-induced hematopoietic damage remains elusive. Here, we report that benzene exposure causes hematopoietic damage in a dose-dependent manner and is associated with disturbances in gut microbiota-long chain fatty acids (LCFAs)-inflammation axis. C57BL/6J mice exposed to benzene for 45 days were found to have a significant reduction in whole blood cells and the suppression of hematopoiesis, an increase in Bacteroides acidifaciens and a decrease in Lactobacillus murinus. Recipient mice transplanted with fecal microbiota from benzene-exposed mice showed potential for hematopoietic disruption, LCFAs, and interleukin-5 (IL-5) elevation. Abnormally elevated plasma LCFAs, especially palmitoleic acid (POA) exacerbated benzene-induced immune-inflammation and hematopoietic damage via carnitine palmitoyltransferase 2 (CPT2)-mediated disorder of fatty acid oxidation. Notably, oral administration of probiotics protects the mice against benzene-induced hematopoietic toxicity. In summary, our data reveal that the gut microbiota-POA-IL-5 axis is engaged in benzene-induced hematopoietic damage. Probiotics might be a promising candidate to prevent hematopoietic abnormalities from benzene exposure.

2024-12-31·RENAL FAILURE

Mesangial cell-derived CircRNAs in chronic glomerulonephritis: RNA sequencing and bioinformatics analysis

Article

作者: Fan, Ji Hui ; Li, Xiao Min

BACKGROUND:

Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis.

METHODS:

Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT.

RESULTS:

The expression of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells.

CONCLUSIONS:

Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.

348

项与 IL-5 相关的新闻（医药）

2024-09-19

·GBIHealth

国产首款！康诺亚IL-4Rα单抗康悦达开出首张处方

药械追踪 No.1 / 默沙东K药在美获批恶性胸膜间皮瘤新适应证默沙东（MSD；NYSE:MRK）近日宣布，旗下PD-1抑制剂可瑞达（帕博利珠单抗）新适应证申请已获得美国FDA批准，用于联合培美曲塞与铂类化疗一线治疗不可切除的晚期或转移性恶性胸膜间皮瘤（MPM）的成年患者。此次批准主要是基于II/III期研究KEYNOTE-483的积极数据。恶性间皮瘤是一种相对罕见的癌症，一般发生在胸部、腹部、心脏以及睾丸等部位内膜。据估计，2022年全球新诊断的恶性间皮瘤患者超过30000例，而死亡人数超过25000例。MPM发生在肺内层，是间皮瘤最常见的一种形式，占比约为75%。MPM往往进展迅速，患者的5年生存率仅为12.8%（美国）。 ->点击阅读原文，解锁完整双语新闻 No.2 / 国产首款！康诺亚IL-4Rα单抗康悦达开出首张处方 2024年9月18日，康诺亚宣布，旗下IL-4Rα抗体药物康悦达（司普奇拜单抗注射液）开出全国首张处方。司普奇拜单抗注射液是以IL-4Rα为靶点的单克隆抗体药物，也是首款国产获批的IL-4R抗体药物。司普奇拜单抗于2024年9月12日宣布获国家药品监督管理局批准上市，用于治疗外用药控制不佳或不适合外用药治疗的成人中重度特应性皮炎。司普奇拜单抗将在各地陆续进入临床应用，现已发货至全国多地，上海、广州、成都等多个城市多地也将同步开出当地首张处方。 ->点击阅读原文，解锁完整双语新闻 No.3 / 阿斯利康重磅疗法本瑞利珠单抗再获FDA批准，用于罕见病EGPA 阿斯利康（LON/NASDAQ：AZN）近日宣布，旗下靶向白细胞介素 5（IL-5）的单克隆抗体本瑞利珠单抗（benralizumab）在美国获批新适应证，可用于治疗罕见的嗜酸性肉芽肿性多血管炎（EGPA）。嗜酸性肉芽肿性多血管炎（EGPA）是一种可累及全身多个系统的、少见的自身免疫性疾病,主要表现为外周血及组织中嗜酸粒细胞增多、浸润及中小血管的坏死性肉芽肿性炎症。大约50%的EGPA患者也患有成人发病的严重嗜酸性哮喘（SEA）。2017年，本瑞利珠单抗被批准用于治疗SEA。 ->点击阅读原文，解锁完整双语新闻企业动态 No.1 / 欧加隆12亿美元收购Dermavant，囊获银屑病外用乳膏本维莫德欧加隆（NYSE:OGN）近日宣布，将全面收购Roivant（Nasdaq: ROIV）旗下专注于皮肤病学的公司Dermavant。经过此次收购，欧加隆将获得Dermavant的本维莫德乳膏（Tapinarof 1%），这是一种用于局部治疗斑块状银屑病的芳香烃受体（AhR）激动剂，目前其用于特应性皮炎（AD）的上市申请正在审评中。此次收购交易总价值高达12亿美元，包括1.75亿美元的预付款，获批AD适应证后支付7500万美元，9.5亿美元的商业里程碑付款，以及向Dermavant股东支付的净销售额特许权使用费。根据协议，欧加隆将获得本维莫德乳膏（Tapinarof 1%）的全球权利（不包括中国和日本）。 ->点击阅读原文，解锁完整双语新闻全球医疗情报领导者解锁隐藏在数据中的商业潜力关于 G B I ” 自从2002年成立以来，GBI始终以技术为驱动，为药企、器械及行业相关服务商提供贯穿生命周期的全球药品市场竞争数据、全球行业资讯、HCPs洞察、全国医疗器械数据等商业信息与洞察，助力企业在进行战略布局和决策时，脱颖而出。历经20余年的深耕细作GBI已成为95%以上跨国药企、国内头部药企、咨询与投资机构等医疗圈灯塔用户值得信赖的长期合作伙伴。联系我们投稿 | 发稿 | 媒体合作 ▶ zhangxinyue13@baidu.com 数据库 | 咨询服务 | 资讯追踪 ▶ 点击左下“阅读原文”完成表单填写点击阅读原文，解锁完整双语新闻

并购上市批准申请上市

2024-09-18

·药明康德

阿斯利康重磅疗法再获FDA批准，近六成患者症状缓解

▎药明康德内容团队编辑阿斯利康（AstraZeneca）今日宣布，其重磅抗体疗法Fasenra（benralizumab）已获得美国FDA的获批，用于治疗嗜酸性肉芽肿性多血管炎（EGPA）的成年患者。EGPA是一种免疫介导的罕见血管炎，可导致多器官损伤，未经治疗可能致命。新闻稿指出，这是FDA批准的第二款治疗EGPA的生物制品。 FDA的批准主要根据3期临床试验MANDARA的积极结果，结果已发表在《新英格兰医学杂志》上。该研究比较了Fasenra与IL-5单抗Nucala（mepolizumab）用于治疗复发或难治性EGPA患者中疗效和安全性。试验结果显示，接近60%的Fasenra治疗患者达到了疾病缓解（remission），与活性对照组相比达到非劣效性标准。此外，41%的Fasenra治疗患者完全停用了口服皮质类固醇（OCS），而在活性对照组中这一比例为26%（差异为16%；95% CI：1，31）。在MANDARA试验中，Fasenra的安全性和耐受性与已知的药物安全性一致。 Fasenra是一款与嗜酸性粒细胞表面表达的IL-5Rα相结合的单克隆抗体。通过与IL-5Rα相结合，它能够募集天然杀伤细胞，通过诱发嗜酸性粒细胞的细胞凋亡过程来迅速清除这些细胞。目前，它已在包括美国、日本、欧盟和中国在内的80多个国家和地区获批作为严重嗜酸性粒细胞哮喘（SEA）的附加维持治疗。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] FASENRA approved in the US for eosinophilic granulomatosis with polyangiitis. Retrieved September 18, 2024, from https://www.businesswire.com/news/home/20240918601834/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床结果临床3期

2024-09-18

·FiercePharma

AstraZeneca's Fasenra plays catch-up with GSK's Nucala, gaining FDA nod for rare autoimmune disease

AstraZeneca's Fasenra, which generated $1.6 billion in sales last year got a boost with an FDA approval to treat eosinophilic granulomatosis with polyangiitis (EGPA), a rare, immune-mediated vascular disorder. Since GSK’s Nucala and AstraZeneca’s Fasenra were approved two years apart to treat patients with severe asthma, the IL-5 inhibitors have engaged in a spirited market battle, with one key difference: While Nucala has added three indications since its original FDA nod in 2015, Fasenra has been shut out in its attempts to expand to new diseases.That changed on Tuesday however, as the FDA signed off on Fasenra for patients with eosinophilic granulomatosis with polyangiitis (EGPA), a rare, immune-mediated vascular disorder that can damage various organs and can be fatal if left untreated.Nucala is the only other drug approved in the indication. GSK gained that nod from the FDA in 2017. Fasenra won over the U.S. regulator by showing non-inferiority to Nucala in the phase 3 MANDARA study in 140 patients with relapsed or refractory EPGA.On establishing non-inferiority on the trial’s primary objective, Fasenra helped 59% of patients achieve remission at both weeks 36 and 48, compared with 57% for Nucala, according to Fasenra’s updated FDA label. Some other key metrics favored AZ’s medicine. For example, 41% of those who took Fasenra were able to eliminate steroids from their treatment regimen, compared to 26% of those on Nucala.“What’s key is that this was the first head-to-head study of biologics ever,” Donna Carstens, M.D., AZ’s senior medical director, respiratory, said in an interview. “In a clinical trial of this, albeit smaller magnitude but a disease state that’s rare and has an umbrella effect on severe eosinophilic asthma, it’s huge.” Another key difference in the study was the dosing. While patients on Fasenra received one 30-mg subcutaneous injection every four weeks, those on Nucala took three 100-mg injections once every four weeks.Carstens explained how drugs from the same treatment class can have such different dosing requirements.“Our mechanism of action is indeed different to that of [Nucala]. They block the cytokine, we actually eliminate the eosinophils,” Carstens said. “We know with a 30-mg dose from a pharmacodynamics standpoint, that we get very efficient reduction in eosinophil counts, which are the main inflammatory cell in this disease.”EGPA, which was formerly known as Churg-Strauss syndrome, affects roughly 118,000 people worldwide and can often be undetected.“Ninety-five percent of the cases present with severe asthma and sinus disease and nasal polyps. So, if you’re not looking beyond managing the asthma then you may miss this,” Carstens said. “The eosinophils are typically much higher than you would see in someone with severe eosinophilic asthma. So, it’s important to have that recognition that this is something else because of the potential significant multi-organ dysfunction and impact.” Fasenra was approved in 2017 but AZ came up short in its attempts to expand its label to chronic obstructive pulmonary disorder (COPD), rhinosinusitis and eosinophilic esophagitis, where it cleared the remission bar in a trial but failed to meet its other objective, which was to relieve swallowing issues called dysphagia.Meanwhile, in addition to its approvals to treat severe asthma and EGPA, Nucala gained nods from the FDA to treat hypereosinophilic syndrome (HES) in 2020 and rhinosinusitis in 2021.Fasenra still has held its own in the market, with sales (PDF) reaching $1.6 billion, which was an increase of 12% from 2022. Meanwhile, GSK reported sales (PDF) of Nucala at £1.655 ($2.2 billion) for 2023 which was an increase of 18% year over year.