Genome-wide association study identifies five loci associated with lung function

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and co…

Response to mepolizumab treatment is sustained across 4-weekly dosing periods

Background Mepolizumab (100 mg delivered s.c. every 4 weeks) is indicated for add-on maintenance treatment for patients with severe eosinophilic asthma. Mepolizumab has been shown to reduce exacerbations and the requirement for daily oral corticosteroids, and improve asthma control and symptoms. However, data on the durability of the response to mepolizumab during dosing periods are limited. The aim of this study was to investigate the efficacy profile in patients with severe eosinophilic asthma over the 4-weekly dosing period for various fixed mepolizumab doses. Methods This was a post hoc analysis of data from the phase IIb/III DREAM study. Patients ≥12 years of age with severe eosinophil…

WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial

BACKGROUND: Some patients with severe asthma have recurrent asthma exacerbations associated with eosinophilic airway inflammation. Early studies suggest that inhibition of eosinophilic airway inflammation with mepolizumab-a monoclonal antibody against interleukin 5-is associated with a reduced risk of exacerbations. We aimed to establish efficacy, safety, and patient characteristics associated with the response to mepolizumab. METHODS: We undertook a multicentre, double-blind, placebo-controlled trial at 81 centres in 13 countries between Nov 9, 2009, and Dec 5, 2011. Eligible patients were aged 12-74 years, had a history of recurrent severe asthma exacerbations, and had signs of eosinophil…

Effective Management of Severe Asthma with Biologic Medications in Adult Patients: A Literature Review and International Expert Opinion

International audience; Severe asthma often remains uncontrolled despite effective treatments and evidence-based guidelines. A group of global experts in asthma and biologic medications from nine countries considered the most relevant clinical variables to manage severe asthma in adult patients and guide treatment choice. The resulting recommendations address the investigation of biomarker levels (blood eosinophil count along with fractional concentration of exhaled nitric oxide [FeNO]), clinical features (oral corticosteroid [OCS] dependency, specific comorbid disease entities associated with severe type 2 asthma), and safety considerations. Current evidence suggests that biomarkers, inclu…

Mepolizumab for eosinophilic chronic obstructive pulmonary disease

BACKGROUNDPatients with chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype may benefit from treatment with mepolizumab, a monoclonal antibody directed against interleukin-5.METHODSWe performed two phase 3, randomized, placebo-controlled, double-blind, parallel-group trials comparing mepolizumab (100 mg in METREX, 100 or 300 mg in METREO) with placebo, given as a subcutaneous injection every 4 weeks for 52 weeks in patients with COPD who had a history of moderate or severe exacerbations while taking inhaled glucocorticoid-based triple maintenance therapy. In METREX, unselected patients in the modified intention-to-treat population with an eosinophilic phenotype were …

Late Breaking Abstract - Dose-ranging study of mepolizumab in eosinophilic COPD

Background: Patients with eosinophilic COPD & frequent exacerbations may benefit from mepolizumab (MEP) treatment. Objective: Assess efficacy & safety of 2 MEP doses vs placebo (PBO) in COPD with blood eosinophils ≥150 cells/µL [screening] or ≥300 cells/µL [prior yr], history of ≥2 moderate/≥1 severe exacerbations & ICS+≥2 bronchodilator maintenance therapies (ICS+MT). Methods: Phase III, randomised, PBO-controlled, double-blind, parallel-group trial (METREO); patients received SC MEP 100mg, MEP 300mg or PBO plus ICS+MT, every 4 wks for 52 wks. Primary endpoint: rate/yr of moderate (systemic corticosteroids/antibiotics)/severe(hospitalisation or death) exacerbations. Secondary endpoints inc…

Clinical Development of Mepolizumab for the Treatment of Severe Eosinophilic Asthma: On the Path to Personalized Medicine.

The development of mepolizumab, an anti-IL-5 monoclonal antibody for the treatment of severe eosinophilic asthma, is an example of a clinical development program that evolved over time based on sound, basic scientific principles. Initial clinical data on the effects of mepolizumab on lung function in a general asthmatic population were disappointing. However, it became clear that mepolizumab may be more effective against other clinical endpoints, particularly asthma exacerbations, in patients with more severe disease. Furthermore, a developing understanding of asthma disease pathobiology led to the identification of an appropriate target population and predictive biomarker for mepolizumab t…