Dupilumab and tezepelumab in severe refractory asthma: new opportunities DOI Creative Commons
Beatrice Ragnoli, Jaymin B. Morjaria, Patrizia Pignatti

et al.

Therapeutic Advances in Chronic Disease, Journal Year: 2022, Volume and Issue: 13, P. 204062232210973 - 204062232210973

Published: Jan. 1, 2022

Bronchial asthma is a chronic inflammatory condition with increasing prevalence worldwide that may present as heterogeneous phenotypes defined by the T2-mediated pattern of airway inflammation T2-high and T2-low asthma. Severe refractory includes subset asthmatic patients who fail to control their disease despite maximal therapy represent group needing marked resource utilization hence be eligible add-on biological therapies. Among new biologics, we focused our attention on two monoclonal antibodies: dupilumab, exerting dual blockade cytokine (interleukin (IL)-4 IL-13) signaling; tezepelumab, acting at higher level preventing binding thymic stromal lymphopoietin (TSLP) its receptor, thus blocking TSLP, IL-25, IL-33 signaling, modulating T2 immune responses. With different mechanisms action, these biologics important options provide an enhanced personalized treatment regimen. Several clinical trials have been conducted testing efficacy safety dupilumab in severe showing improvements lung function, control, reducing exacerbations. Similar results were reported tezepelumab that, differently from acts irrespectively eosinophilic or non-eosinophilic phenotype. In this review, overview most highlights regarding characteristics mechanism action critical review principal (Phase II III) studies concluded those still progress.

Language: Английский

Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory response DOI Creative Commons
Marc Duchesne, Isobel Okoye, Paige Lacy

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 14, 2022

The exposure of the airway epithelium to external stimuli such as allergens, microbes, and air pollution triggers release alarmin cytokines IL-25, IL-33 thymic stromal lymphopoietin (TSLP). TSLP interact with their ligands, IL-17RA, IL1RL1 TSLPR respectively, expressed by hematopoietic non-hematopoietic cells including dendritic cells, ILC2 endothelial fibroblasts. Alarmins play key roles in driving type 2-high, a lesser extent 2-low responses, asthma. In addition, studies which each these three alarmins were targeted allergen-challenged mice showed decreased chronicity type-2 driven disease. Consequently, ascertaining mechanism activity upstream mediators has implications for understanding outcome therapies designed counteract alleviate downstream 2-high low effector responses. Furthermore, identifying factors shift balance between elicitation eosinophilic asthma low, neutrophilic-positive/negative is essential. support efforts, observations from NAVIGATOR trial imply that targeting patients tezepelumab results reduced exacerbations, improved lung function control this review, we will discuss mechanisms surrounding secretion IL-33, how influences allergic cascade. We also review detail alarmin-receptor/co-receptor interactions modulate inflammation. Current strategies target alarmins, efficacy inflammatory phenotype be discussed.

Language: Английский

Citations

55
Severe Asthma Remissions Induced by Biologics Targeting IL5/IL5r: Results from a Multicenter Real-Life Study DOI Open Access
Angelantonio Maglio, Carolina Vitale, Corrado Pelaia

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2455 - 2455

Published: Jan. 27, 2023

Add-on biological therapy has proven to be effective in many patients with severe eosinophilic asthma. In this observational multicenter retrospective study, we report the results obtained mepolizumab and benralizumab asthmatics treated for 12 months a real-life setting. these patients, peripheral eosinophil levels, pulmonary function trends, exacerbation rates, systemic corticosteroid use, symptom control were evaluated during observation period, understand which met all criteria order considered disease remission. The percentage of remittent was 30.12% mepolizumab-treated subgroup, while benralizumab-treated complete remission 40%, after months. study confirm efficacy anti-IL-5 biologic drugs treatment asthma

Language: Английский

Citations

37
Bullous pemphigoid: The role of type 2 inflammation in its pathogenesis and the prospect of targeted therapy DOI Creative Commons
Luyao Zhang, Zihua Chen, Lanting Wang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Bullous pemphigoid (BP) is an autoimmune disease that mainly occurs in the elderly, severely affecting their health and life quality. Traditional therapy for BP based on systemic use of corticosteroids, but long-term corticosteroids results a series side effects. Type 2 inflammation immune response largely mediated by group innate lymphoid cells, type T helper eosinophils, inflammatory cytokines, such as interleukin (IL)-4, IL-5 IL-13. Among patients with BP, levels immunoglobulin E eosinophils are significantly increased peripheral blood skin lesions, suggesting pathogenesis tightly related to inflammation. To date, various targeted drugs have been developed treat diseases. In this review, we summarize general process inflammation, its role potential therapeutic targets medications The content review may contribute development more effective fewer effects treatment BP.

Language: Английский

Citations

17
Switching Biological Therapies in Severe Asthma DOI Open Access
Giulia Scioscia, Santi Nolasco, Raffaele Campisi

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9563 - 9563

Published: May 31, 2023

Currently, three classes of monoclonal antibodies targeting type 2 inflammation pathways are available in Italy for the treatment severe asthma: anti-IgE (Omalizumab), anti-IL-5/anti-IL-5Rα (Mepolizumab and Benralizumab), anti-IL-4Rα (Dupilumab). Numerous randomized controlled trials (RCTs) real-life studies have been conducted to define their efficacy identify baseline patients’ characteristics potentially predictive favorable outcomes. Switching another antibody is recommended case a lack benefits. The aim this work review current knowledge on impact switching biological therapies asthma as well predictors response or failure. Almost all information about from previous comes setting. In studies, most frequent initial biologic was Omalizumab patients who were switched because suboptimal control with therapy more likely higher blood eosinophil count exacerbation rate despite OCS dependence. choice suitable may be guided by patient’s clinical history, biomarkers endotype (mainly eosinophils FeNO), comorbidities (especially nasal polyposis). Due overlapping eligibility, larger investigations characterizing profile benefiting different needed.

Language: Английский

Citations

17
Monoclonal Antibodies Targeting Alarmins: A New Perspective for Biological Therapies of Severe Asthma DOI Creative Commons
Corrado Pelaia, Giulia Pelaia, Federico Longhini

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(9), P. 1108 - 1108

Published: Aug. 29, 2021

Alarmins are innate cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), which mainly produced by airway epithelium exert a prominent role in asthma pathobiology. In particular, several environmental factors such as allergens, cigarette smoking, airborne pollutants, infectious agents trigger the release of alarmins, turn act upstream activators pro-inflammatory pathways underlying type 2 (T2-high) asthma. Indeed, alarmins directly activate group lymphoid cells (ILC2), eosinophils, basophils, mast also stimulate dendritic to drive commitment naïve T helper (Th) towards Th2 immunophenotype. Therefore, TSLP, IL-33, IL-25 represent suitable targets for add-on therapies severe Within this context, fully human anti-TSLP monoclonal antibody tezepelumab has been evaluated very promising randomized clinical trials. Tezepelumab other anti-alarmins thus likely become, near future, valuable therapeutic options biological treatment uncontrolled

Language: Английский

Citations

34
Comparative Efficacy and Safety of Tezepelumab and Other Biologics in Patients with Inadequately Controlled Asthma According to Thresholds of Type 2 Inflammatory Biomarkers: A Systematic Review and Network Meta-Analysis DOI Creative Commons
Koichi Andō, Y Fukuda, Akihiko Tanaka

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(5), P. 819 - 819

Published: Feb. 26, 2022

The anti-thymic stromal lymphopoietin antibody (tezepelumab) has therapeutical potential for inadequately controlled asthma. However, evidence comparing tezepelumab with other biologics is scarce. To address this issue, we performed a network meta-analysis to compare and rank the efficacy of five treatments (tezepelumab, dupilumab, benralizumab, mepolizumab, placebo) in overall participants subgroups stratified by thresholds type 2 inflammatory biomarkers, including peripheral blood eosinophil count (PBEC) fractional exhaled nitric oxide (FeNO). primary endpoints were annualized exacerbation rate (AER) any adverse events (AAEs). In ranking assessment using surface under cumulative curve (SUCRA) AER, ranked highest across (based on PBEC FeNO level thresholds). A significant difference was observed between dupilumab patient subgroup < 150, benralizumab ≥ 300 ≥150, respectively. There no incidence AAEs each pair treatment arms. These results provide basis development strategies asthma may guide basic, clinical, or translational research.

Language: Английский

Citations

27
Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study DOI Creative Commons
Jiamin Sun,

Shiyao Bai,

Jieyu Zhao

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

Background Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving variety cells and cellular components, that manifests clinically as recurrent episodes wheezing, shortness breath, with or without chest tightness cough, airway hyperresponsiveness, variable airflow limitation. The number people has reached 358 million worldwide causes huge economic loss. However, there subset patients who are not sensitive to existing drugs have many adverse effects. Therefore, it’s important find new for patients. Methods Publications related biologics in published from 2000 2022 were retrieved Web Science Core Collection. search strategies follows: topic: TS=(biologic* OR “biologic* product*” therap*” biotherapy* agent*” Benralizumab “MEDI-563” Fasenra “BIW-8405” Dupilumab SAR231893 “SAR-231893” Dupixent REGN668 “REGN-668” Mepolizumab Bosatria “SB-240563” SB240563 Nucala Omalizumab Xolair Reslizumab “SCH-55700” SCH55700 “CEP-38072” CEP38072 Cinqair “DCP-835” DCP835 Tezspire “tezepelumab-ekko” “AMG-157” tezspire “MEDI-9929” “MEDI-19929” MEDI9929 Itepekimab “REGN-3500”OR REGN3500 “SAR-440340”OR SAR440340 Tralokinumab “CAT-354” Anrukinzumab “IMA-638” Lebrikizumab “RO-5490255”OR “RG-3637”OR “TNX-650”OR “MILR1444A”OR “MILR-1444A”OR”PRO301444”OR “PRO-301444”OR Pitrakinra altrakincept “AMG-317”OR”AMG317” Etokimab Pascolizumab “IMA-026”OR Enokizumab “MEDI-528”OR “7F3COM-2H2” 7F3COM2H2 Brodalumab “KHK-4827” “KHK4827”OR “AMG-827”OR Siliq Ligelizumab “QGE-031” QGE031 Quilizumab Talizumab “TNX-901” TNX901 Infliximab Etanercept “PRS-060”) AND TS=asthma*. document type was set articles review language restriction English. Three different analysis tools including one online platform, VOS viewer1.6.18, CiteSpace V 6.1.R1 software used conduct this bibliometric study. Results This study included 1,267 English papers 244 journals 2,012 institutions 69 countries/regions. Omalizumab, benralizumab, mepolizumab, tezepelumab relation research hotspots field. Conclusion systematically uncovers holistic picture literature biologic treatment over past 20 years. We consulted scholars order understand key information field perspective bibliometrics, which we believe may greatly facilitate future

Language: Английский

Citations

15
Thymic Stromal Lymphopoietin (TSLP), Its Isoforms and the Interplay with the Epithelium in Allergy and Asthma DOI Open Access
Sylwia Smolińska, Darío Antolín‐Amérigo, Florin‐Dan Popescu

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(16), P. 12725 - 12725

Published: Aug. 12, 2023

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that has emerged as critical player in the development and progression of allergy asthma. It primarily produced by epithelial cells functions potent immune system activator. TSLP acts through interaction with its receptor complex, composed (TSLPR) interleukin-7 alpha chain (IL-7Rα), activating downstream complex signalling pathways. The major isoform, known long-form (lfTSLP), upregulated airway epithelium patients allergic diseases. More research warranted to explore precise mechanisms which short-form (sfTSLP) regulates responses. Understanding dynamic interplay between dysfunctional provides insights into underlying asthma pathogenesis. Targeting represents an important therapeutic strategy, it may upstream disrupt inflammatory cascade alleviate symptoms associated inflammation.

Language: Английский

Citations

15
Development of an inhaled anti-TSLP therapy for asthma DOI Creative Commons
Paul M. O’Byrne, Reynold A. Panettieri, Christian Taube

et al.

Pulmonary Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 78, P. 102184 - 102184

Published: Dec. 16, 2022

Language: Английский

Citations

21
Tezepelumab improved chronic rhinosinusitis with nasal polyps in a Patient with aspirin exacerbated respiratory disease DOI Creative Commons

Yuga Yamashita,

Kosuke Terada,

Yuka Kodama

et al.

Respiratory Medicine Case Reports, Journal Year: 2024, Volume and Issue: 50, P. 102041 - 102041

Published: Jan. 1, 2024

Patients with chronic rhinosinusitis nasal polyps (CRSwNP) and aspirin-exacerbated respiratory disease (AERD) have more severe sinus than those without AERD. CRSwNP associated type 2 inflammation AERD can be difficult to control standard medical therapy surgery.

Language: Английский

Citations

4