Stratification of eosinophilic asthma patients treated with reslizumab and GINA Step 4 or 5 therapy

Reslizumab, an anti-interleukin-5 monoclonal antibody, significantly reduces exacerbation frequency and improves lung function, asthma control and quality of life in adults with severe eosinophilic asthma, as demonstrated in Phase III studies. This secondary analysis assessed reslizumab's efficacy in patients receiving baseline treatment per Global Initiative for Asthma (GINA) Step 4 and Step 5 guidelines. Pooled data from duplicate, Phase III, reslizumab versus placebo studies in patients with severe eosinophilic asthma (blood eosinophils ≥400 cells·µL−1) were stratified by baseline therapy. Efficacy assessments were exacerbation rates and changes from baseline forced expiratory volume in …

Reslizumab Treatment for Moderate to Severe Asthma with Elevated Blood Eosinophil Levels

Reslizumab (RES) in asthma patients (pts) with severe eosinophilic asthma stratified by GINA asthma steps 4 and 5: Analysis of two phase 3, placebo (PBO)-controlled trials

Background: RES reduced exacerbation frequency and improved lung function and asthma control in pts with inadequately controlled asthma and elevated blood eosinophils (EOS) in two PBO-controlled, phase 3 trials (Castro et al. Lancet Resp Med 2015). Aims/objectives: To determine the efficacy of RES in asthma pts stratified by GINA Step 4 (G4) and Step 5 (G5) categories of asthma severity. Methods: Pooled data from two 52-week, PBO-controlled trials of RES (3mg/kg IV Q4W) in pts with inadequately controlled asthma and blood EOS ≥400/µL on inhaled corticosteroid (ICS) ± another controller; primary results have been reported. Current analysis includes pts stratified by G4 (medium/high-dose ICS …

GINA 2019: a fundamental change in asthma management

GINA no longer recommends treating adults/adolescents with asthma with short-acting bronchodilators alone. Instead, they should receive symptom-driven (in mild asthma) or a daily corticosteroid-containing inhaler, to reduce risk of severe exacerbations.http://bit.ly/310LLzE

Tralokinumab did not demonstrate oral corticosteroid-sparing effects in severe asthma

Long-term oral corticosteroid (OCS) use in patients with severe asthma is associated with significant adverse effects.This 40-week, randomised, double-blind trial evaluated the OCS-sparing potential of tralokinumab in patients with severe, uncontrolled asthma requiring maintenance OCS treatment plus inhaled corticosteroids/long-acting β2-agonists. Overall, 140 patients were randomised to tralokinumab 300 mg or placebo (n=70 in each group) administered subcutaneously every 2 weeks. The primary end-point was percentage change from baseline in average OCS dose at week 40, while maintaining asthma control. Secondary end-points included proportion of patients with a prescribed maintenance OCS do…

Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials

Elevated numbers of blood eosinophils are a risk factor for asthma exacerbations. Reslizumab is a humanised anti-interleukin 5 monoclonal antibody that disrupts eosinophil maturation and promotes programmed cell death. We aimed to assess the efficacy and safety of reslizumab in patients with inadequately controlled, moderate-to-severe asthma.We did two duplicate, multicentre, double-blind, parallel-group, randomised, placebo-controlled phase 3 trials. Both trials enrolled patients with asthma aged 12-75 years (from 128 clinical research centres in study 1 and 104 centres in study 2) from Asia, Australia, North America, South America, South Africa, and Europe, whose asthma was inadequately c…

Global Initiative for Asthma (GINA) Strategy 2021 - Executive summary and rationale for key changes

Funder: Global Initiative for Asthma

Budesonide/Formoterol Maintenance And Reliever Therapy At Two Different Maintenance Doses: Effect On Fractional Excretion Of Nitric Oxide (FENO)

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 x 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may p…

Omalizumab as alternative to chronic use of oral corticosteroids in severe asthma.

Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective…

Care pathways for the selection of a biologic in severe asthma.

Physicians need care pathways to select a biologic in type 2 severe asthma (omalizumab, mepolizumab, reslizumab) http://ow.ly/pygw30gB7Bv

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice: Review

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Eosinophilic and Noneosinophilic Asthma

Background Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. Research Question What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? Study Design and Methods This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a pre…

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associatio…

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P <5 x 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispani…

Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Funder: British Lung Foundation (BLF); doi: https://doi.org/10.13039/501100000351