Search

Globally, a small proportion (5–12%) of asthma patients are estimated to have severe disease. However, severe asthma accounts for disproportionately high healthcare resource utilization. The Global Initiative for Asthma (GINA) management committee recommends treating patients with asthma with inhaled corticosteroids plus long-acting β2-agonists and, when needed, adding a long-acting muscarinic receptor antagonist or biologic agent. Five biologics, targeting different effectors in the type 2 inflammatory pathway, are approved for asthma treatment. However, biologics have not been compared against each other or add-on inhaled therapies in head-to-head clinical trials. As a result, their positioning versus that of current and anticipated small-molecule strategies is largely unknown. Furthermore, with the emergence of biomarkers for predicting response to biologics, a more personalized treatment approach—currently lacking with inhaled therapies—may be possible. To gain perspective, we reviewed recent advances in asthma pathophysiology, phenotypes, and biomarkers; the place of biologics in the management and personalized treatment of severe asthma; and the future of biologics and small-molecule drugs. We propose an algorithm for the stepwise treatment of severe asthma based on recommendations in the GINA strategy document that accounts for the broad range of phenotypes targeted by inhaled therapies and the specificity of biologics. In the future, both biologics and small molecules will continue to play key roles in the individualized treatment of severe asthma. However, as targeted therapies, their application will continue to be focused on patients with certain phenotypes who meet the specific criteria for use as identified in pivotal clinical trials. [ABSTRACT FROM AUTHOR]

Background: Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.Methods: This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George's Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline.Results: Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44-68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27-0.59 points, and improved St George's Respiratory Questionnaire total score by 5.0-11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1-286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup.Conclusions: Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity.Trial Registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318. [ABSTRACT FROM AUTHOR]

This article, published in the journal Allergy, discusses a study that explores the existence of different subtypes of asthma based on immune signaling pathways. The study recruited 200 asthmatic patients and measured levels of certain cytokines in their sputum. The results revealed two distinct pathways of immune signaling, each associated with different patterns of cytokine expression. One pathway was linked to more severe disease and frequent hospitalizations. The study suggests that understanding these subtypes could lead to more targeted treatments for asthma. However, further research is needed to confirm these findings. The article also includes a table with various data points related to asthma patients, providing valuable information for research purposes. [Extracted from the article]

Background: Previous research has shown greater efficacy of dupilumab in patients with uncontrolled asthma and type 2 inflammation. We analyzed dupilumab's efficacy in patients from the TRAVERSE study with or without evidence of allergic asthma and type 2 inflammation per current GINA guidelines (≥150 eosinophils/μL or FeNO ≥20 ppb). Methods: All patients aged ≥12 years who rolled over from the placebo‐controlled QUEST study (NCT02414854) to TRAVERSE (NCT02134028) received add‐on dupilumab 300 mg every 2 weeks for up to 96 weeks. We assessed annualized severe asthma exacerbation rates (AERs) and changes from parent‐study baseline (PSBL) in pre‐bronchodilator FEV1 and 5‐item asthma control questionnaire (ACQ‐5) score in patients with moderate‐to‐severe type 2 asthma with and without evidence of allergic asthma at PSBL. Results: In TRAVERSE, dupilumab consistently reduced AER across all subgroups. By Week 96, dupilumab increased pre‐bronchodilator FEV1 from PSBL by 0.35–0.41 L in patients receiving placebo during QUEST (placebo/dupilumab) and 0.34–0.44 L in those receiving dupilumab during QUEST (dupilumab/dupilumab) with an allergic phenotype at baseline. In patients without evidence of allergic asthma, pre‐bronchodilator FEV1 improved by 0.38–0.41 L and 0.33–0.37 L, respectively. By Week 48, ACQ‐5 scores decreased from PSBL by 1.63–1.69 (placebo/dupilumab) and 1.74–1.81 (dupilumab/dupilumab) points across subgroups with allergic asthma, and 1.75–1.83 (placebo/dupilumab) and 1.78–1.86 (dupilumab/dupilumab) in those without. Conclusions: Long‐term treatment with dupilumab reduced exacerbation rates and improved lung function and asthma control in patients with asthma with type 2 inflammation as per current GINA guidance and irrespective of evidence of allergic asthma. [ABSTRACT FROM AUTHOR]