Comparative effectiveness of omalizumab, mepolizumab, and dupilumab in asthma: A target trial emulation

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 151(5), P. 1269 - 1276

Published: Feb. 3, 2023

Multiple mAbs are currently approved for the treatment of asthma. However, there is limited evidence on their comparative effectiveness.

Language: Английский

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Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 19, 2024

The etiology of allergy is closely linked to type 2 inflammatory responses ultimately leading the production allergen-specific immunoglobulin E (IgE), a key driver many allergic conditions. At high level, initial allergen exposure disrupts epithelial integrity, triggering local inflammation via alarmins including IL-25, IL-33, and TSLP, which activate innate lymphoid cells as well other immune secrete cytokines IL-4, IL-5 IL-13, promoting Th2 cell development eosinophil recruitment. dependent B activation promotes IgE, stably binds basophils mast cells. Rapid degranulation these upon re-exposure leads symptoms. Recent advances in our understanding molecular cellular mechanisms underlying pathophysiology have significantly shaped therapeutic intervention strategies. In this review, we highlight targets within cascade with particular focus on past, current future treatment approaches using monoclonal antibodies. Specific targeting alarmins, IgE has shown varying degrees clinical benefit different indications asthma, chronic spontaneous urticaria, atopic dermatitis, rhinosinusitis nasal polyps, food allergies eosinophilic esophagitis. While multiple antibodies been approved for use, scientists are still working ways improve approaches. Here, provide context understand strategies their limitations, discussing both knowledge gaps promising directions enhancing efficacy disease management.

Language: Английский

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How I do it. Choosing the right biologic for the right patient with severe asthma

CHEST Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

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Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types

Journal of Asthma and Allergy, Journal Year: 2024, Volume and Issue: Volume 17, P. 219 - 236

Published: March 1, 2024

Abstract: Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% people with asthma have severe disease, associated higher risk hospitalizations, greater healthcare costs, poorer outcomes. Patients generally require high-dose inhaled corticosteroids additional controller medications achieve control; however, patients remain uncontrolled despite this intensive treatment. The treatment has improved understanding pathways phenotypes as well advent targeted biologic therapies. Tezepelumab, monoclonal antibody, blocks thymic stromal lymphopoietin, an epithelial cytokine that multifaceted effects on initiation persistence inflammation pathophysiology. Unlike other treatments, tezepelumab demonstrated efficacy across phenotypes, magnitude varying by phenotype. Here we describe anti-inflammatory most relevant asthma. Across clinical studies, reduced annualized exacerbation rates versus placebo 63– 71% in eosinophilic asthma, 58– 68% allergic 67– 34– 49% type 2-low 31– 41% oral corticosteroid-dependent Furthermore, all these reducing exacerbations requiring hospitalizations or emergency department visits placebo. In who commonly multiple drivers may modulate airway more extensively, available biologics block only specific downstream components cascade. Plain Language Summary: characterized immune response leading inflammation. People react different triggers develop types protein called lymphopoietin (TSLP) plays important role leads signs symptoms TSLP released lining triggers, driving chain reaction, narrowing tightening, increased inflammation, worsening symptoms, attack. Tezepelumab antibody (a protein) prevents from attaching its receptor, thereby blocking activity, symptoms. add-on medicine for aged 12 years older not controlled their current medicines. article, discuss how work example T2-low We also effective types, through reduction attacks improvement lung function, symptom control, quality life, fewer Keywords: exacerbations, eosinophilic, allergic, 2, corticosteroid-dependent, hyperresponsiveness

Language: Английский

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Integrative Roles of Pro‐Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: Feb. 24, 2025

ABSTRACT Asthma has become more appreciated for its heterogeneity with studies identifying type 2 and non‐type phenotypes/endotypes that ultimately lead to airflow obstruction, airway hyperresponsiveness, remodeling. The pro‐inflammatory environment in asthma influences smooth muscle (ASM) structure function. ASM a vast repertoire of inflammatory receptors that, upon activation, contribute prominent features asthma, notably immune cell recruitment hypercontractility, proliferation, migration, extracellular matrix protein deposition. These responses can be mediated by both (e.g., IL‐4, IL‐13, TSLP) TNFα, IFNγ, IL‐17A, TGFβ) cytokines, highlighting roles phenotypes/endotypes. In recent years, there been considerable advances understanding how cytokines promote dysfunction impair responsiveness therapy, corticosteroids long‐acting β2‐adrenergic receptor agonists (LABAs). Transcriptomic analyses on human cells tissues have expanded our knowledge this area but also raised new questions regarding role asthma. review, we discuss corticosteroids, LABAs affect function, particular focus changes gene expression transcriptional programs

Language: Английский

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Lung function trajectories in a cohort of patients with moderate‐to‐severe asthma on mepolizumab, omalizumab, or dupilumab

Allergy, Journal Year: 2024, Volume and Issue: 79(5), P. 1195 - 1207

Published: Jan. 2, 2024

Abstract Background Lung function is an independent predictor of mortality. We evaluated the lung trajectories a cohort patients with asthma receiving biologic therapy. Methods identified 229 monoclonal antibody‐naïve adult moderate‐to‐severe who initiated omalizumab, mepolizumab, or dupilumab between 2010 and 2022 in large healthcare system Boston, MA. Generalized additive mixed models were used to estimate during 156 weeks following initiation. Response was defined as improvement FEV 1 decrease ≤0.5% per year. The Kaplan–Meier estimator assess time no additional responders. All adjusted for age, sex, body mass index, smoking status, baseline exacerbation rate, blood eosinophil count. Results Eighty‐eight 76 65 dupilumab. Baseline count highest mepolizumab group (405 cells/mcL) lowest omalizumab (250 cells/mcL). Both FVC improved (FEV + 20 mL/year; +43 mL/year). For there initial first year followed by decline overall loss −44 mL/year −32 mL/year. dupilumab, both (+61 mL/year) (+74 over time. Fifty percent group, 58% 72% median responders 24 48 57 Conclusion In this clinical cohort, had beneficial effects on distinct post‐initiation trajectories.

Language: Английский

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Comparative Effectiveness of Mepolizumab, Benralizumab, and Dupilumab among Patients with Difficult-to-Control Asthma: A Multicenter Retrospective Propensity-matched Analysis

Annals of the American Thoracic Society, Journal Year: 2024, Volume and Issue: 21(6), P. 866 - 874

Published: Jan. 19, 2024

: Rationale The comparative effectiveness of biologics used as add-on therapy in the management difficult-to-control asthma is unclear. Objective To compare dupilumab, mepolizumab and benralizumab among patients with asthma. Methods Retrospective multicenter cohort study adult started on or from a electronic health record claims-based database between October 19, 2018 September 30, 2022. Propensity score matching was to minimize bias non-randomized treatment assignment; prespecified alpha level set at 0.017 account for three primary comparisons. exposure interest new initiation mepolizumab. outcome rate exacerbation year following biologic modeled using negative binomial approach. Results Among 893,668 who were prescribed an inhaled corticosteroid least 12 years old, (65% female, mean age 49), 3,943 1,902 benralizumab, 2,012 without alternative indication therapy. After matching, there 1,805 each group comparisons dupilumab 1,865 mepolizumab, 1,721 benralizumab. For all pairwise comparisons, covariates well balanced after (all standardized differences <0.1). Patients initiating had significantly lower exacerbations (1.07/year) compared (1.47/year) ratio 0.73 [95% confidence interval (CI) 0.63-0.85] also (1.04/year 1.45/year) 0.72 [0.62-0.84]. There no statistically significant difference (1.40/year) (1.41/year) 1.00 [CI 0.85-1.17]. Conclusions In newly initiated therapy, associated decreased

Language: Английский

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Tezepelumab: An Anti-Thymic Stromal Lymphopoietin Monoclonal Antibody for the Treatment of Asthma

Immunotherapy, Journal Year: 2023, Volume and Issue: 15(17), P. 1435 - 1447

Published: Sept. 19, 2023

Asthma is a common chronic respiratory disease in which epithelial cytokines and airway inflammation play critical pathophysiological roles. Thymic stromal lymphopoietin (TSLP), an cytokine, central the initiation persistence of asthma. Tezepelumab human immunoglobulin G2λ (IgG2λ) monoclonal antibody developed for treating moderate-to-severe asthma by specifically binding to TSLP preventing its receptor on inflammatory cells. In this narrative review, we describe results clinical trials that evaluated pharmacokinetics, pharmacodynamics, efficacy safety tezepelumab patients with We also introduce ongoing as well future investigating use other indications.Asthma long-term causes cells lung. One (proteins) involved called thymic (TSLP). This cytokine produced epithelium, layer covering tract lungs, where it activates new drug blocks activity lungs helps reduce symptoms, such coughing breathlessness. article, investigated how works, safety, people moderate or severe are now underway asthma, allergies diseases.

Language: Английский

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Potential drug targets for asthma identified through mendelian randomization analysis

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 13, 2025

Abstract Background The emergence of new molecular targeted drugs marks a breakthrough in asthma treatment, particularly for severe cases. Yet, options moderate-to-severe treatment remain limited, highlighting the urgent need novel therapeutic drug targets. In this study, we aimed to identify targets using Mendelian randomization method and large-scale genome-wide association data (GWAS). Methods We utilized GWAS from UK Biobank (comprising 56,167 patients 352,255 control subjects) FinnGen cohort (including 23,834 228,085 subjects). Genetic instruments 734 plasma proteins 154 cerebrospinal fluid were derived recently published GWAS. Bidirectional analysis, Steiger filtering, colocalization, phenotype scanning employed reverse causal inference detection, further substantiating results. A protein-protein interaction network was also constructed reveal potential associations between medications. Results Under Bonferroni significance conditions, analysis revealed relationships seven asthma. plasma, observed that an increase one standard deviation IL1R1[1.30 (95% CI 1.20–1.42)], IL7R[1.07 1.04–1.11)], ECM1[1.03 1.02–1.05)], CD200R1[1.18 1.09–1.27)] associated with increased risk asthma, while ADAM19 [0.87 0.82–0.92)] found be protective. brain, each 10-fold IL-6 sRa [1.29 1.15–1.45)] Layilin [0.61 0.51–0.73)] None exhibited relationship. Colocalization indicated ECM1 (coloc.abf-PPH4 = 0.953), 0.966), layilin 0.975) shared same genetic variation as Conclusion relationship exists genetically determined protein levels IL1R1, IL7R, ECM1, CD200R1, ADAM19, sRa, (LAYN) Moreover, identified may serve attractive especially (LAYN). However, research is required comprehensively understand roles these occurrence progression

Language: Английский

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Tezepelumab for asthma with current or previous smoking habit: Case series

Journal of Allergy and Clinical Immunology Global, Journal Year: 2025, Volume and Issue: 4(2), P. 100420 - 100420

Published: Jan. 18, 2025

Language: Английский

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