Tezepelumab in severe asthma: a profile of its use DOI Creative Commons

Yahiya Y. Syed

Drugs & Therapy Perspectives, Journal Year: 2023, Volume and Issue: 39(12), P. 393 - 403

Published: Dec. 1, 2023

Tezepelumab (tezepelumab-ekko; TEZSPIRE®), a first-in-class monoclonal antibody targeting thymic stromal lymphopoietin, represents novel, effective and generally well tolerated treatment option for patients with severe asthma across wide range of phenotypes. In randomized, double-blind, phase 2 (PATHWAY) 3 (NAVIGATOR) trials, subcutaneous tezepelumab demonstrated significant reduction in annualized exacerbation rate among uncontrolled asthma. The efficacy was seen broad different endotypes phenotypes, including eosinophilic noneosinophilic asthma, allergic type-2 low sustained over up to 104 weeks. is tolerated, the most common adverse reactions being pharyngitis, arthralgia back pain. Asthma complex condition caused by chain inflammatory events airway. Thymic lymphopoietin (TSLP) one proteins that sits at top initiates downstream actions. TEZSPIRE®) blocks action TSLP, thus exerting broad-spectrum anti-asthmatic activity. Administered subcutaneously once every 4 weeks, significantly reduces high as which typically unresponsive biologics. years. tolerated. novel subgroups, regardless their phenotypes or biomarkers levels.

Language: Английский

Co-Expression Analysis of Airway Epithelial Transcriptome in Asthma Patients with Eosinophilic vs. Non-Eosinophilic Airway Infiltration DOI Open Access
Paweł Koźlik,

Sylwia Buregwa-Czuma,

Izabela Zawlik

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3789 - 3789

Published: Feb. 14, 2023

Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic feature frequent in severe asthma, bronchial epithelial transcriptome, functional structural measures of compared gene expression, spirometry, cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), blood bronchoalveolar lavage (BAL) cytokines n = 40 moderate (EA) non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA showed similar extent remodeling as NEA but had an increased expression genes involved immune response (e.g., KIR3DS1), reactive oxygen species generation (GYS2, ATPIF1), cell activation proliferation (ANK3), cargo transporting (RAB4B, CPLX2), tissue (FBLN1, SOX14, GSN), lower integrity GJB1) histone acetylation (SIN3A). Genes co-expressed were antiviral responses ATP1B1), migration (EPS8L1, STOML3), adhesion (RAPH1), epithelial-mesenchymal transition (ASB3), hyperreactivity (FBN3, RECK), several linked genome- MRPL14, ASB3) or epigenome-wide association studies (CLC, GPI, SSCRB4, STRN4). Signaling pathways inferred from co-expression pattern associated with TGF-β/Smad2/3, E2F/Rb, Wnt/β-catenin).

Language: Английский

Citations

2
抗TSLP薬 DOI
Mizuho Nagao

Nihon Shoni Arerugi Gakkaishi The Japanese Journal of Pediatric Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 38(2), P. 225 - 232

Published: June 19, 2024

Thymic stromal lymphopoietin(TSLP)は,上皮細胞由来のサイトカインであり,自然免疫および獲得免疫の経路を介して2型炎症の誘導に重要な役割を果たす.テゼペルマブは,TSLPがTSLP受容体に結合するのを阻害するヒトIgG2モノクローナル抗体であり,喘息の新しい生物学的製剤である.テゼペルマブの喘息における有効性と作用機序を評価するために,PATHWAY,NAVIGATOR,NOZOMI,UPSTREAM,CASCADE,SOURCE,DESTINATIONなどといったいくつかの臨床試験が実施されている.これらの結果は,テゼペルマブが幅広いターゲットの生物学的製剤であり,表現型に関係なく吸入ステロイド(ICS)ではコントロール困難な喘息患者に有効であることが期待されているが,テゼペルマブの作用機序や非2型表現型の患者における有効性,経口ステロイド依存性喘息への影響などはまだ不明であり,さらなる研究が必要である.小児の喘息治療における生物学的製剤の選択はまだ確立されておらず,患者の病態に応じた適切な治療法の選択ができるよう検討が必要である.

Citations

0
Positioning tezepelumab for patients with severe asthma: from evidence to unmet needs DOI Creative Commons
Carlo Lombardi, Marcello Cottini,

Annamaria Bosi

et al.

Journal of International Medical Research, Journal Year: 2024, Volume and Issue: 52(11)

Published: Nov. 1, 2024

Several endotypes of severe asthma with predominantly type 2 inflammation can be distinguished by the immune pathways driving inflammatory processes. However, in absence inflammation, is less clearly defined and generally associated poor responses to conventional anti-asthmatic therapies. Studies have shown that disruption epithelial barrier triggers increases permeability. A key aspect this process cells release alarmin cytokines, including interleukin (IL)-25, IL-33, thymic stromal lymphopoietin (TSLP), response allergens infections. Among these TSLP has been identified as a potential therapeutic target for asthma, leading development new biologic, tezepelumab (TZP). By blocking TSLP, TZP may produce wide-ranging effects. Based on positive clinical trial results, appears offer promising, safe, effective treatment approach. This narrative review examines evidence treating TZP, analyses findings, provides clinicians practical insights into identifying patients who respond best novel biologic therapy.

Language: Английский

Citations

0
Tezepelumab (Tezspire) DOI Open Access

CADTH

Canadian Journal of Health Technologies, Journal Year: 2023, Volume and Issue: 3(2)

Published: Feb. 6, 2023

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well patient clinician perspectives, a drug or class. The inform non-binding recommendations that help guide decisions Canada's federal, provincial, territorial governments, with exception Quebec. This review assesses Tezepelumab (Tezspire), 210 mg, 110 mg/mL solution for subcutaneous injection. Indication (proposed): indicated an add-on maintenance treatment in adults adolescents 12 years older severe asthma.

Language: Английский

Citations

0
Tezepelumab in severe asthma: a profile of its use DOI Creative Commons

Yahiya Y. Syed

Drugs & Therapy Perspectives, Journal Year: 2023, Volume and Issue: 39(12), P. 393 - 403

Published: Dec. 1, 2023

Tezepelumab (tezepelumab-ekko; TEZSPIRE®), a first-in-class monoclonal antibody targeting thymic stromal lymphopoietin, represents novel, effective and generally well tolerated treatment option for patients with severe asthma across wide range of phenotypes. In randomized, double-blind, phase 2 (PATHWAY) 3 (NAVIGATOR) trials, subcutaneous tezepelumab demonstrated significant reduction in annualized exacerbation rate among uncontrolled asthma. The efficacy was seen broad different endotypes phenotypes, including eosinophilic noneosinophilic asthma, allergic type-2 low sustained over up to 104 weeks. is tolerated, the most common adverse reactions being pharyngitis, arthralgia back pain. Asthma complex condition caused by chain inflammatory events airway. Thymic lymphopoietin (TSLP) one proteins that sits at top initiates downstream actions. TEZSPIRE®) blocks action TSLP, thus exerting broad-spectrum anti-asthmatic activity. Administered subcutaneously once every 4 weeks, significantly reduces high as which typically unresponsive biologics. years. tolerated. novel subgroups, regardless their phenotypes or biomarkers levels.

Language: Английский

Citations

0