Response to biologics along a gradient of T2 involvement in patients with severe asthma: a data-driven biomarker clustering approach.

Background: Asthma with low levels of T2-biomarkers is poorly understood.

Objective: To characterize severe asthma phenotypes and compare pre- to post-biologic change in asthma outcomes along a gradient of T2-involvement.

Methods: This was a registry-based, cohort study including data from 24 countries.

Urinary thromboxane and isoprostane levels are elevated in symptom-high T2-biomarker-low severe asthma.

Background: ∼5-10% of patients with asthma have severe disease. A proportion remain symptomatic despite suppression of T2-related inflammation but what drives persistent symptoms remains unclear. Eicosanoids exert a functional role in pulmonary inflammation.

Effects of obesity on response to asthma biologic treatment: Longitudinal data from the United Kingdom Severe Asthma Registry.

Background: Obesity is a common co-morbidity associated with poor outcomes in severe asthma.

Objective: We aimed to determine whether obesity is associated with an altered response to severe asthma biologic agents.

Methods: We analysed data from the UK Severe Asthma Registry, a large UK-wide cohort of patients attending regional severe asthma services.

Disease Trajectory and Treatment Escalation in Asthma: A Retrospective Analysis of Data From the Optimum Patient Care Research Database (OPCRD).

Background: Approximately 5% of patients with asthma have severe disease. Treatment escalation may occur despite symptoms not being due to asthma, leading to comorbidities occurring.

Objective: To explore factors associated with treatment escalation to Global Initiative for Asthma (GINA): step 4/5 in patients with asthma.

Investigating the Association Between Biologic Initiation and Medication Adherence in Severe Asthma: An Analysis of Linked Data.

Background: Poor adherence to inhaled therapy is common among patients with asthma. Findings from previous studies exploring inhaled corticosteroid (ICS) adherence in biologic-treated populations are inconsistent and have not investigated the long-term outcomes.

Objective: To assess the long-term impact of introducing biologics on ICS/long-acting β-agonist (LABA) adherence and to investigate the effect of poor ICS/LABA adherence on clinical outcomes among biologic-treated patients.

Analysis of airway inflammation demonstrates a mechanism for T2-biologic failure in asthma.

Background: Targeted type 2 (T2) biologics have transformed asthma care, but the clinical response to biologic therapy varies between patients.

Objective: We sought to assess airways inflammation in T2-high asthmatic patients treated with anti-IL-5 biologics to investigate whether differential mechanism of airway inflammation explains varied response to biologics.

Methods: Proteomic analysis (Olink, 1463 protein panel) and high-sensitivity cytokine analysis (ELISAs) were performed on induced sputum from T2-high severe asthmatic patients in the UK multicenter Mepolizumab EXacerbation study.

Pre-biologic assessment of adherence in severe asthma and association with biologic continuation: a UK Severe Asthma Registry Study.

Background: Biologic therapies are approved for uncontrolled severe asthma despite good adherence to inhaled corticosteroids (ICS) and additional controllers. We examined the adherence assessments used across UK Severe Asthma Centres (SACs) and their relationship with biologic continuation and response.

Methods: UK SACs completed a quantitative survey on adherence assessment practices in 2022.

Exploring the carbon footprint of severe asthma and change after biologic therapy initiation: an analysis of Northern Irish data.

Background: The carbon footprint of severe asthma and the impact of biologic therapy in this population is unknown.

Methods: This was a retrospective cohort study in adults with severe asthma, using data from the Northern Ireland Regional Severe Asthma Service (September 2015-November 2021). We calculated annual greenhouse gas (GHG) emissions (carbon dioxide equivalent) for asthma-related medications and healthcare resource utilisation, compared patient characteristics by GHG quartile, calculated GHG change post-biologic initiation, and explored the relationship between GHG change and clinical response.

Real-world uptake of nirsevimab, RSV maternal vaccine, and RSV vaccines for older adults: a systematic review and meta-analysis.

Background: In clinical trials, recently introduced respiratory syncytial virus (RSV) immunisation products have shown high efficacy in preventing severe RSV outcomes. Implementing successful immunisation programmes is however key to realising these benefits in real-world settings. We aimed to investigate uptake of the long-acting monoclonal antibody nirsevimab, the RSV maternal vaccine, and RSV vaccines for older adults in countries where immunisation programmes have been introduced, and to explore how uptake varies between countries and population subgroups.

Prediction Pathway for Severe Asthma Exacerbations: A Bayesian Network Analysis.

Background: Accurate risk prediction of exacerbations is pivotal in severe asthma management. Multiple risk factors are at play, but the pathway of risk prediction remains unclear.

Research Question: How do the interplays of clinically relevant predictors lead to severe exacerbations in patients with severe asthma?

Study Design And Methods: Patients with severe asthma (n = 6,814, aged ≥ 18 years), biologic naive, were identified from the Severe Asthma Registry (2017-2021).

Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.

Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom).

Exploring the Long-Term Utility of Remotely Monitored FeNO Suppression Testing in Severe Asthma.

Background: Confirmation of optimal inhaled corticosteroid use is essential before initiating biologic therapy. Fractional exhaled nitric oxide (FeNO) suppression testing (FeNOSuppT) is a proven phenotyping technique; however, its long-term effect on clinical outcomes remains unclear.

Objectives: To assess the real-world feasibility of delivering FeNOSuppT alongside digital inhaler monitoring and to examine its effect on biologic initiation and clinical outcomes.

Impact of Biologics Initiation on Oral Corticosteroid Use in the International Severe Asthma Registry and the Optimum Patient Care Research Database: A Pooled Analysis of Real-World Data.

Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited.

Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings.

Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2).

Incidence and prevalence of asthma, chronic obstructive pulmonary disease and interstitial lung disease between 2004 and 2023: harmonised analyses of longitudinal cohorts across England, Wales, South-East Scotland and Northern Ireland.

Background: We describe the epidemiology of asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) from 2004 to 2023 in England, Wales, Scotland and Northern Ireland (NI) using a harmonised approach.

Methods: Data from the National Health Service England (NHSE), Clinical Practice Research Datalink Aurum in England, Secure Anonymised Information Linkage Databank in Wales, DataLoch in South-East Scotland and the Honest Broker Service in NI were used. A harmonised approach to COPD, asthma and ILD case definitions, study designs and study populations across the four nations was performed.

International Severe Asthma Registry (ISAR): 2017-2024 Status and Progress Update.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research.

Clinical remission attainment, definitions, and correlates among patients with severe asthma treated with biologics: a systematic review and meta-analysis.

Background: Clinical remission has emerged as an important treatment goal in severe asthma; however, studies have reported variable attainment due to differences in study populations, definitions, and methods. We aimed to perform a systematic review and meta-analysis of clinical remission attainment, definitions, and correlates among patients with severe asthma who have been treated with biologics.

Methods: In this systematic review and meta-analysis, we searched Web of Science, Embase, and MEDLINE, using the keywords "asthma" and "remission", for studies published between database inception and June 13, 2024, that reported clinical remission among patients with severe asthma treated with biologics.

Longitudinal Assessment of Glucocorticoid Toxicity Reduction in Patients With Severe Asthma Treated With Biologic Therapies.

Background: Toxicities associated with oral corticosteroids (OCS) are well described. Targeted biologics for severe asthma (SA) substantially reduce OCS exposure with the potential to reduce cumulative OCS-related toxicities. The Glucocorticoid Toxicity Index (GTI) systematically assesses OCS-related toxicity; the GTI Aggregate Improvement Score (AIS) is a bidirectional measure of total toxicity change with a minimal clinically important difference (MCID) of ≤-10.

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).

Clinical remission with biologic therapies in severe asthma: a matter of definition.

https://bit.ly/42IOVbA

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.