Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial.

Background: Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, which has shown increased expression in patients with chronic obstructive pulmonary disease (COPD) compared with healthy individuals. We aimed to assess the efficacy and safety of tezepelumab in patients with moderate to very severe COPD despite receiving triple inhaled therapy.

Methods: COURSE was a double-blind, randomised, placebo-controlled, phase 2a trial across 90 sites in ten countries in Asia, Europe, and North America.

Efficacy of tezepelumab in patients with severe asthma and persistent airflow obstruction.

Background: Persistent airflow obstruction (PAO) in patients with asthma can be difficult to treat. Tezepelumab blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. This analysis evaluated the efficacy of tezepelumab in patients with severe, uncontrolled asthma and PAO.

Predicting Asthma Exacerbations Using Machine Learning Models.

Introduction: Although clinical, functional, and biomarker data predict asthma exacerbations, newer approaches providing high accuracy of prognosis are needed for real-world decision-making in asthma. Machine learning (ML) leverages mathematical and statistical methods to detect patterns for future disease events across large datasets from electronic health records (EHR). This study conducted training and fine-tuning of ML algorithms for the real-world prediction of asthma exacerbations in patients with physician-diagnosed asthma.

Machine Learning Approaches to Predict Asthma Exacerbations: A Narrative Review.

The implementation of artificial intelligence (AI) and machine learning (ML) techniques in healthcare has garnered significant attention in recent years, especially as a result of their potential to revolutionize personalized medicine. Despite advances in the treatment and management of asthma, a significant proportion of patients continue to suffer acute exacerbations, irrespective of disease severity and therapeutic regimen. The situation is further complicated by the constellation of factors that influence disease activity in a patient with asthma, such as medical history, biomarker phenotype, pulmonary function, level of healthcare access, treatment compliance, comorbidities, personal habits, and environmental conditions.

Efficacy of Tezepelumab in Severe, Uncontrolled Asthma: Pooled Analysis of the PATHWAY and NAVIGATOR Clinical Trials.

Tezepelumab reduced exacerbations in patients with severe, uncontrolled asthma across a range of baseline blood eosinophil counts and fractional exhaled nitric oxide levels, and irrespective of allergy status, in the phase 2b PATHWAY (Study to Evaluate the Efficacy and Safety of MEDI9929 [AMG 157] in Adult Subjects With Inadequately Controlled, Severe Asthma; NCT02054130) and phase 3 NAVIGATOR (Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma; NCT03347279) trials. To examine the efficacy and safety of tezepelumab in additional clinically relevant subgroups using pooled data from PATHWAY and NAVIGATOR. PATHWAY and NAVIGATOR were randomized, double-blind, placebo-controlled trials with similar designs.

Toward a Predict and Prevent Approach in Obstructive Airway Diseases.

Asthma and chronic obstructive pulmonary disease are currently diagnosed and treated after the demonstration of variable airflow limitation and symptoms. Under this framework, undiagnosed and unchecked airway inflammation is associated with recurrent acute attacks, airway remodeling, airflow limitation, adverse effects of corticosteroids, and impaired quality of life, ultimately leading to the collection of side effects termed "people remodeling." This one-size-fits-all damage control approach aims to control symptoms and treat exacerbations rather than modify the underlying disease process.

Targeting TSLP in Asthma.

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine implicated in the initiation and persistence of inflammatory pathways in asthma. Released in response to a range of epithelial insults (eg, allergens, viruses, bacteria, pollutants, and smoke), TSLP initiates multiple downstream innate and adaptive immune responses involved in asthma inflammation. Inhibition of TSLP is postulated to represent a novel approach to treating the diverse phenotypes and endotypes of asthma.

Real-world impact of mepolizumab in patients with life-threatening asthma: US insurance claims database analysis.

Purpose: Patients with life-threatening asthma typically experience recurrent exacerbations, are dependent on oral corticosteroids (OCSs), and have considerable asthma-related health care costs. Data on the impact of mepolizumab on exacerbations and OCS use in patients with life-threatening asthma in real-world clinical practice are limited. This study assessed the impact of mepolizumab on exacerbation rates and OCS use in patients with life-threatening asthma in a real-word setting.

A real-world study of inhaled corticosteroid use in patients with severe eosinophilic asthma treated with mepolizumab.

Background: Mepolizumab is a humanized anti-interleukin-5, monoclonal antibody approved for the treatment of patients with severe eosinophilic asthma (SEA). There is limited evidence that mepolizumab can reduce inhaled corticosteroid (ICS) use in these patients.

Objective: To investigate changes in ICS use and clinical outcomes in patients with SEA who initiated mepolizumab treatment.

Factors leading to discontinuation of biologic therapy in patients with severe asthma.

Objective: To assess patient- and physician-reported reasons for discontinuing biologic therapy among patients with severe asthma from a real-world US cohort.

Methods: This retrospective analysis surveyed US physicians and their patients with severe asthma who were receiving/had previously received biologic therapy between August and December 2019. Physicians managing ≥3 patients with asthma per month completed surveys on disease management, demographics, exacerbation history, and biologic adherence for eligible patients.

Real-world effectiveness of mepolizumab in patients with severe asthma and associated comorbidities.

Background: Patients with severe asthma frequently have associated comorbidities, which can compound existing symptoms, complicating asthma management.

Objective: To describe the real-world effectiveness of mepolizumab in patients with severe asthma stratified by common overlapping comorbidities.

Methods: This was a retrospective analysis of patients with asthma from the MarketScan Commercial and Medicare Supplemental Database initiating mepolizumab treatment (index date).

Real-world evidence: Patient views on asthma in respiratory specialist clinics in America.

Background: Approximately 30% to 50% of patients with moderate/severe asthma have inadequately controlled disease despite adherence to inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) therapy. Data on prevalence and burden of uncontrolled asthma in specialty settings are lacking.

Objective: To evaluate the prevalence and burden of uncontrolled asthma in respiratory specialist clinics in the United States.

Phase 2, randomised placebo-controlled trial to evaluate the efficacy and safety of an anti-GM-CSF antibody (KB003) in patients with inadequately controlled asthma.

Objectives: We wished to evaluate the effects of an antigranulocyte-macrophage colony-stimulating factor monoclonal antibody (KB003) on forced expiratory volume in 1 s (FEV1), asthma control and asthma exacerbations in adult asthmatics inadequately controlled by long-acting bronchodilators and inhaled/oral corticosteroids.

Settings: 47 ambulatory asthma care centres globally.

Primary Outcome Measures: Change in FEV1 at week 24.

The impact of exacerbation frequency on mortality following acute exacerbations of COPD: a registry-based cohort study.

Objective: To examine the association between exacerbation frequency and mortality following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Design: Cohort study using medical databases.

Setting: Northern Denmark.

A randomized trial of benralizumab, an antiinterleukin 5 receptor α monoclonal antibody, after acute asthma.

Background: Patients with frequent asthma exacerbations resulting in emergency department (ED) visits are at increased risk for future exacerbations. We examined the ability of 1 dose of benralizumab, an investigational antiinterleukin 5 receptor α monoclonal antibody, to reduce recurrence after acute asthma exacerbations.

Methods: In this randomized, double-blind, placebo-controlled study, eligible subjects presented to the ED with an asthma exacerbation, had partial response to treatment, and greater than or equal to 1 additional exacerbation within the previous year.

Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study.

Background: Persistent eosinophilic airway inflammation in asthma increases the risk of exacerbations. In a phase 2b dose-ranging study, we aimed to assess the efficacy and safety of benralizumab, an anti-interleukin 5 receptor α monoclonal antibody that depletes blood and airway eosinophils, in adults with uncontrolled eosinophilic asthma.

Methods: We did a randomised, controlled, double-blind, dose-ranging phase 2b study.

Effects of benralizumab on airway eosinophils in asthmatic patients with sputum eosinophilia.

Background: Many asthmatic patients exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding IL-5 receptor α, inducing apoptosis through antibody-dependent cell-mediated cytotoxicity.

Objectives: We sought to evaluate the safety of benralizumab in adults with eosinophilic asthma and its effects on eosinophil counts in airway mucosal/submucosal biopsy specimens, sputum, bone marrow, and peripheral blood.

Hospitalization with acute exacerbation of chronic obstructive pulmonary disease and associated health resource utilization: a population-based Danish cohort study.

Objective: Health resource utilization (HRU) and outcomes associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are not well described. Therefore, a population-based cohort study was conducted to characterize patients hospitalized with AECOPD with regard to HRU, mortality, recurrence, and predictors of readmission with AECOPD.

Methods: Using Danish healthcare databases, this study identified COPD patients with at least one AECOPD hospitalization between 2005-2009 in Northern Denmark.