Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype.

Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.

Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care.

Overcoming Barriers to Remission in Severe Eosinophilic Asthma: Two-Year Real-World Data With Benralizumab.

Background: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood.

Impact of comorbidities on EQ-5D quality-of-life index in severe asthma.

Background: Severe asthma pathology encompasses a wide range of pulmonary and extrapulmonary treatable traits with a high prevalence of comorbidities. Although asthma-specific health-related quality-of-life measures are most sensitive to changes in asthma control, generic measures, such as EQ-5D-5L (EuroQol 5-Dimension 5-Level questionnaire), are potentially better for capturing the impact of comorbidities.

Objective: We sought to examine the impact of pulmonary and extrapulmonary treatable traits on quality of life at initial severe asthma assessment, and to compare the characteristics of those patients whose quality of life does and does not improve during follow-up at severe asthma centers.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts.

Background: Type 2 low-severe asthma phenotype is often a result of corticosteroid-overtreated type 2 disease owing to persistent symptoms, often unrelated to asthma and unlikely to respond to high-dose corticosteroid treatment.

Objective: This study aimed to characterize patients with severe asthma with low eosinophil counts (<300 cells/μL) and describe their disease burden and treatment across health care settings in the United Kingdom.

Methods: A retrospective cohort study of patients with severe asthma using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients according to the latest blood eosinophil count (BEC).

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma.

Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13).

Immunogenicity of biologics used in the treatment of asthma.

Objective: Asthma is a major global disease affecting adults and children, which can lead to hospitalization and death due to breathing difficulties. Although targeted monoclonal antibody therapies have revolutionized treatment of severe asthma, some patients still fail to respond. Here we critically evaluate the literature on biologic therapy failure in asthma patients with particular reference to anti-drug antibody production, and subsequent loss of response, as the potential primary cause of drug failure in asthma patients.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

Background: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging.

Objective: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response.

International Variation in Severe Exacerbation Rates in Patients With Severe Asthma.

Background: Exacerbation frequency strongly influences treatment choices in patients with severe asthma.

Research Question: What is the extent of the variability of exacerbation rate across countries and its implications in disease management?

Study Design And Methods: We retrieved data from the International Severe Asthma Registry, an international observational cohort of patients with a clinical diagnosis of severe asthma. We identified patients aged ≥ 18 years who did not initiate any biologics prior to baseline visit.

Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma.

Background: There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma.

Objective: To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma.

Methods: This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.

Long-term symptom profiles after COVID-19 other acute respiratory infections: an analysis of data from the COVIDENCE UK study.

Background: Long COVID is a well recognised, if heterogeneous, entity. Acute respiratory infections (ARIs) due to other pathogens may cause long-term symptoms, but few studies compare post-acute sequelae between SARS-CoV-2 and other ARIs. We aimed to compare symptom profiles between people with previous SARS-CoV-2 infection, people with previous non-COVID-19 ARIs, and contemporaneous controls, and to identify clusters of long-term symptoms.

Ethnic variation in asthma phenotypic presentation and outcomes: a cross-sectional analysis of the UK Biobank.

Ethnic disparities exist within asthma; however, country of birth is rarely investigated. We described demographic and clinical characteristics by ethnicity and country of birth within the UK Biobank. Lung function and asthma hospitalisations were similar for white, black and North-East Asian participants, however, South-East (SE) Asians more commonly had an FEV below the lower limits of normal (LLN; 53.

Bringing the treatable traits approach to primary care asthma management.

Asthma continues to be a major cause of illness with a significant mortality, despite its increasing range of treatments. Adoption of a treatable traits approach in specialist centres has led to improvements in control of asthma and reduced exacerbations in patients with severe asthma. However, most patients with this illness, particularly those with mild-to-moderate asthma, are cared for in primary care according to guidelines that emphasise the use of pharmacotherapeutic ladders uniformly implemented across all patients.

Experiences of Diagnosis, Symptoms, and Use of Reliever Inhalers in Patients With Asthma and Concurrent Inducible Laryngeal Obstruction or Breathing Pattern Disorder: Qualitative Analysis of a UK Asthma Online Community.

Background: Breathing pattern disorders (BPDs) and inducible laryngeal obstruction (ILO) cause similar symptoms to asthma, including dyspnea and chest tightness, with an estimated prevalence of up to one-fifth of patients with asthma. Both conditions can be comorbid with asthma, and there is evidence that they are misdiagnosed and mistreated as asthma.

Objective: This study aims to explore whether the symptoms of ILO and BPD were topics of discussion in a UK asthma online health community and patient experiences of diagnosis and treatment, in particular their use of reliever inhalers.

Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma.

Background: The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

Background: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone.

Objective: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS.

Methods: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry.

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls.

Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea.

Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period).

Comparative effectiveness of anti-IL5 and anti-IgE biologic classes in patients with severe asthma eligible for both.

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life.

Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R.

Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK).

Background: The imposition of restrictions on social mixing early in the COVID-19 pandemic was followed by a reduction in asthma exacerbations in multiple settings internationally. Temporal trends in social mixing, incident acute respiratory infections (ARI) and asthma exacerbations following relaxation of COVID-19 restrictions have not yet been described.

Methods: We conducted a population-based longitudinal study in 2312 UK adults with asthma between November 2020 and April 2022.