Biologics in severe asthma: a state-of-the-art review

European Respiratory Review, Journal Year: 2025, Volume and Issue: 34(175), P. 240088 - 240088

Published: Jan. 1, 2025

Asthma is considered severe if it remains uncontrolled despite optimal conventional therapy, characterised by poor symptom control, frequent exacerbations and increased exposure to systemic corticosteroids. This has a significant impact on morbidity, mortality healthcare resource utilisation. Recent advances in the understanding of asthma heterogeneity immunopathogenesis have helped delineate precise disease pathways. The discovery these pivotal pathways led development highly effective biologic therapies. Currently available biologics target immunoglobulin E, interleukin (IL)-5/IL-5Rα, IL-4Rα thymic stromal lymphopoietin. Identification specific phenotypes, utilising easily measurable biomarkers, paved way towards personalised precision management. Biologic therapies play role reducing exacerbations, hospitalisations need for maintenance steroids, while also improving quality life patients with asthma. evidence their clinical efficacy comes from randomised controlled trials (RCTs), extension studies, metanalyses real-world data. review synthesises findings early, RCTs subsequent studies following approval safety data completed variety settings, provide practical perspectives application enhance generalisability.

Language: Английский

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Asthma Biologics Across the T2 Spectrum of Inflammation in Severe Asthma: Biomarkers and Mechanism of Action

Journal of Asthma and Allergy, Journal Year: 2025, Volume and Issue: Volume 18, P. 33 - 57

Published: Jan. 1, 2025

Airway inflammation, a hallmark feature of asthma, drives many canonical features the disease, including airflow limitation, mucus plugging, airway remodeling, and hyperresponsiveness. The T2 inflammatory paradigm is firmly established as dominant mechanism asthma pathogenesis, largely due to success inhaled corticosteroids biologic therapies targeting components pathway, IL-4, IL-5, IL-13, thymic stromal lymphopoietin (TSLP). However, up 30% patients may lack signatures meaningful inflammation (ie, low). In T2-low patients, be masked anti-inflammatory treatments or highly variable depending on exposure common triggers such allergens, respiratory infections, smoke pollution. epithelium epithelial cytokines (TSLP, IL-33) are increasingly recognized upstream drivers pathways modulators various effector cells, mast eosinophils, neutrophils, which impact pathological manifestations smooth muscle hypertrophy, hypercontractility, Approved biologics for severe target several distinct mechanisms action, leading differential effects spectrum biomarkers, treatment efficacy (reducing exacerbations, improving lung function, diminishing symptoms). approved anti-asthma primarily immune pathways, with little evidence suggesting benefit non-T2 asthma-associated mediators. Indeed, negative results challenge current assumptions about etiology raise doubts viability popular alternative T17. Novel data have emerged from use treat mediators furthered our understanding pathogenic that drive asthma. This review discusses contribute quantitatively outlines available summarizes challenges clinical trials address

Language: Английский

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Advances in Biologic Therapies for Allergic Diseases: Current Trends, Emerging Agents, and Future Perspectives

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(4), P. 1079 - 1079

Published: Feb. 8, 2025

Biologic therapies have revolutionized the treatment of severe allergic diseases, including asthma, atopic dermatitis (AD), chronic spontaneous urticaria (CSU), rhinosinusitis with nasal polyps (CRSwNP), eosinophilic gastrointestinal diseases (EGIDs), and rhinitis (AR). These molecularly targeted agents provide significant benefits for patients unresponsive to conventional treatments by addressing underlying immune mechanisms, particularly type 2 inflammation driven cytokines such as IL-4, IL-5, IL-13. Recent advancements include biologics targeting alarmins like thymic stromal lymphopoietin (TSLP) IL-33, which may address both non-type inflammation, broadening their therapeutic scope. Despite effectiveness, remain expensive, posing socioeconomic challenges, there are concerns regarding long-term safety inter-individual variability in responses. Promising innovations bispecific antibodies ultra-long-acting under investigation, alongside digital health tools remote biomarker monitoring AI-driven decision support systems, aim enhance personalized care. However, disparities access, underserved populations, underscore need policy reforms affordable biosimilars. This review synthesizes recent findings emerging trends, highlighting evolving role transforming disease management offering insights into future research directions.

Language: Английский

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Eosinophil-Driven vs. Eosinophil-Associated Severe Asthma: Practical Implications for Target Treatment

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1729 - 1729

Published: Feb. 18, 2025

Severe asthma (SA) is a chronic inflammatory condition affecting approximately 10% of asthmatic patients, and eosinophils are considered key pathogenetic actors in significant number patients. Biological therapies have been demonstrated to improve control by decreasing exacerbation rates reducing the use oral corticosteroids. In this context, phenotyping endotyping patients with SA essential for selecting most effective therapeutic approach. For purpose, biomarkers such as IgE, absolute blood eosinophil count, fractional exhaled nitric oxide (FeNO) crucial defining patient's profile. Their integration provides framework classifying into T2-high, T2-mild, or T2-low categories, guiding personalized treatment strategies. By incorporating multiple unified model, it possible better stratify optimize biologic therapy selection, paving way improved outcomes management. This review aims evaluate role particular attention impact eosinophilic inflammation combinatory on decision-making processes selection biological therapies.

Language: Английский

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Clinical remission in severe asthma: lights and shadows on an ambitious goal

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2024, Volume and Issue: 24(4), P. 230 - 236

Published: April 30, 2024

Purpose of review The aim this study was Describe the latest evidence related to concept clinical remission in patients with severe asthma, focusing on lights and shadows concept. Recent findings idea asthma brings about a significant shift way is treated managed. Although there has yet be unanimous agreement among various scientific societies precise definition, can extremely useful advancing treatment disease. Summary Asthma common respiratory condition that affects more than 300 million people globally. It variable symptoms severity levels, 10% experiencing asthma. While have been advancements treatment, poses challenges. approaches focused achieving remission, which goes beyond symptom control address underlying inflammation biological processes. Clinical criteria include absence symptoms, reduced medication usage, normalized inflammatory markers. Various biologic therapies show promise, some remission. However, remission's definition varies globally, hindering standardization valid comparison. Standardizing refining predictive factors are crucial for effective management. Overall, offers hope improved long-term outcomes patients.

Language: Английский

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Effectiveness and Safety of Tezepelumab in a Diverse Population of US Patients with Severe Asthma: Initial Results of the PASSAGE Study

Advances in Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Clinical trials for severe uncontrolled asthma (SUA) often underrepresent or exclude key patient populations. The phase 4 PASSAGE study assesses the effectiveness and safety of tezepelumab in a diverse, real-world US population patients with SUA. is an ongoing, multicenter, single-arm, open-label (≥ 12 years) enrolled participants across phenotypes, based on blood eosinophil counts (BECs) (≥/< 300 cells/µL) perennial aeroallergen sensitization, underrepresented subgroups (Black/African Americans, adolescents, comorbid mild to moderate chronic obstructive pulmonary disease (COPD) smokers [≥ 10 pack-years]). Participants receive 210 mg subcutaneously every weeks 52 weeks. This interim analysis assessed annualized exacerbation rates (AAERs) 12-month baseline period (before starting tezepelumab) treatment period, changes from week 24 pre-bronchodilator (BD) forced expiratory volume 1 second (FEV1), Asthma Control Questionnaire-6 (ACQ-6) score health-related quality life (HRQoL) outcomes. Of 208 this analysis, 41% had BEC ≥ cells/µL, 56% confirmed allergy, 17% were Black/African American, 5% 13% COPD, 23% smokers. AAER decreased by 76% (95% CI (confidence interval): 69, 81) period; comparable reductions observed phenotypes subgroups. least squares mean change pre-BD FEV1 was 0.11 L CI: 0.06, 0.17) overall 0.19 0.12, 0.25) among ≤ 80% predicted. Clinically meaningful improvements ACQ-6 HRQoL No new signals identified. SUA treated demonstrates substantial AAERs subgroups, clinically lung function, control HRQoL. ClinicalTrials.gov identifier, NCT05329194.

Language: Английский

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Thymic Stromal Lymphopoietin (TSLP): Evidence in Respiratory Epithelial-driven Diseases Including Chronic Rhinosinusitis with Nasal Polyps

Current Allergy and Asthma Reports, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 5, 2024

Language: Английский

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Biologics in T2 Severe Asthma: Unveiling Different Effectiveness by Real-World Indirect Comparison

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(16), P. 4750 - 4750

Published: Aug. 13, 2024

Background: Indirect comparison among biologics in severe asthma (SA) is a challenging but desirable goal for clinicians real life. The aim of the study to define characteristics biologic-treated T2-driven-SA population and evaluate effectiveness biologic treatments real-world setting by variation intra/inter-biologic parameters an up 4-year follow-up. Methods: Demographic, clinical, functional, biological were evaluated retrospectively 104 patients recruited until July 2022 at baseline (T0) over maximum 4 years (T4) therapy (omalizumab/OmaG = 41, from T0 T4, mepolizumab/MepoG 26, benralizumab/BenraG 18, T2, dupilumab/DupiG 19, T1). Variations using means paired Delta assessed. Results: At baseline, had high prevalence T2-driven comorbidities, low control test (ACT mean 17.65 ± 4.41), impaired pulmonary function (FEV1 65 18 %pred), frequent exacerbations/year (AEs 3.5 3), OCS dependence (60%). DupiG lower T2 biomarkers/comorbidities AEs, worse FEV1 (57 19 %pred) compared other (p < 0.05). All improved ACT, FEV1%, FVC%, AEs rate, use. FEV1% MepoG BenraG minimal clinically important difference was sustained OmaG MepoG. A significant RV reduction (T1), normalization (T2) airflow limitation found. We observed through inter-biologic pair delta nocturnal awakenings vs. OmaG/MepoG, neutrophils BenraG/DupiG OmaG. Conclusions: unveils clinical functional improvements that may mark different effectiveness. These results highlight preference single another with regard specific treatable traits.

Language: Английский

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Analysis of lipid uptake, storage, and fatty acid oxidation by group 2 innate lymphoid cells

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 21, 2024

Group 2 Innate Lymphoid Cells (ILC2) are critical drivers of both innate and adaptive type immune responses, known to orchestrate processes involved in tissue restoration wound healing. In addition, ILC2 have been implicated chronic inflammatory barrier disorders immunopathologies such as allergic rhinitis asthma. the context allergen-driven airway inflammation recently shown influence local systemic metabolism, well being rich lipid-storing organelles called lipid droplets. However, mechanisms anabolism catabolism remain largely unknown impact these metabolic regulating phenotypes effector functions has not extensively characterized. shaped by their status, determining requirements is understanding role responses associated pathophysiology. We detail here a novel experimental method implementing flow cytometry for large scale analysis fatty acid uptake, storage neutral lipids, oxidation primary murine with complementary morphological using confocal microscopy. By combining microscopy, we can identify characterize phenotype ILC2. Linking metabolism pathways assessment pharmaceutical strategies regulate immunopathologies.

Language: Английский

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Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 9, 2024

Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA IL-17RB subunits, resulting the release Th2 cytokines IL-4, IL-5, IL-9 IL-13 drive an inflammatory response. Therefore, blockage via SM17, novel humanized monoclonal antibody, offers attractive therapeutic target for Th2-mediated diseases, such asthma.

Language: Английский

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