Luis Pérez de Llano

Hospital Universitario Lucus Augusti

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Borja G. Cosío

Hospital Universitario Son Espases

Giorgio Walter Canonica

Humanitas University

David Price

Observational & Pragmatic Research Institute

Liam G. Heaney

Queen's University Belfast

Chin Kook Rhee

Catholic University of Korea

George Christoff

Medical University of Sofia

Mark Hew

Alfred Health

Mona Al‐Ahmad

Ministry of Health

Mohsen Sadatsafavi

Centre for Health Evaluation and Outcome Sciences

Trung N. Tran

AstraZeneca (United States)

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Observational & Pragmatic Research Institute

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Translational Research Institute

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias

Royal Brompton Hospital

Instituto de Salud Carlos III

Hospital Universitario Lucus Augusti

Inserm

Centro de Investigación Biomédica en Red

AstraZeneca (United States)

Complexo Hospitalario Universitario A Coruña

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Real world biologic treatment response in severe asthma: an analysis of the International Severe Asthma Registry (ISAR)

05.01 - Airway pharmacology and treatment (2023)

Tham Le Ghislaine Scélo Trung N. Tran Malin Faregås Neil Martin

Background: Understanding of treatment response to biologic therapy for severe asthma in the real world remains limited. Objective: To examine multiple levels of response to biologic therapy in adults with severe asthma in ISAR. Methods: This multi-country (n=23), registry-based study included patients ≥18 years who initiated biologics (anti-IL5/5R, anti-IgE, anti-IL4/IL13). Response in the 12 months (min. 6 months) post-initiation among impaired patients (as defined in Figure 1) was assessed as: ≥50% reduction in exacerbation rate, ≥50% reduction in LTOCS daily dose, ≥1 level improvement in asthma control, and ≥100 mL increase in FEV1, alone or in combination of 2,3, 4 endpoints. Results: Of total 1986 eligible adults, median age was 54 years, 59.7% were female; 79.7%, 53.6%, 47.4%, and 53.1% of patients achieved response in exacerbation, LTOCS, asthma control, and FEV1, respectively. Treatment response ranged from 43.6% to 10.5% when extending the definition from 2 to 4 endpoints. Greater response was observed in patients treated with anti-IL5/5R and anti-IL4/IL13 (Figure 1). Conclusion: Biologic effectiveness is evidenced as a large proportion of patients achieved response in at least one endpoint. There is still unmet need as the majority were non-responders in composite 4 endpoints. Response varies by definition, thus, multiple endpoints should be considered to fully assess response to biologics.

Clinical endpoint

10.1183/13993003.congress-2023.pa1894

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

Allergy (2024)

Eve Denton Mark Hew Matthew Peters John W. Upham Lakmini Bulathsinhala

Abstract 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). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV 1 ) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super‐response criteria were: FEV 1 increase by ≥500 mL, new well‐controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. Results 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non‐initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV 1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super‐responses. Responses/super‐responses were more frequent in biologic initiators than in non‐initiators; nevertheless, ~40–50% of initiators did not meet response criteria. Conclusions Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non‐initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super‐responses in all outcome domains, 40–50% did not meet the response criteria.

10.1111/all.16178

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Prognostic value of multidimensional indices in ambulatory COPD patients

European Journal of Internal Medicine (2015)

Rafael Golpe Noemí Mengual-Macenlle Irene Martín-Robles Pilar Sanjuán-López Luis Pérez de Llano

BODE index

Obstructive lung disease

Gold standard (test)

10.1016/j.ejim.2015.05.008

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Citations (4)

Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry

The Journal of Allergy and Clinical Immunology In Practice (2021)

Eve Denton David Price Trung N. Tran Giorgio Walter Canonica Andrew Menzies‐Gow

Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis.We characterized biomarker expression in adults with severe asthma.Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/μL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables.Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV1) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis.There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics.

10.1016/j.jaip.2021.02.059

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Citations (86)

Cost-effectiveness of Continuous Positive Airway Pressure Treatment in Moderate-Severe Obstructive Sleep Apnea Syndrome

Archivos de Bronconeumología (2016)

Raquel Poquet Catalá Renata Villoro María Merino Sandra Sangenís Lluís Colomés

Epworth Sleepiness Scale

Hypopnea

10.1016/j.arbr.2016.07.006

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Citations (23)

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

Allergy (2023)

Paul Pfeffer Nasloon Ali Ruth Murray Charlotte Suppli Ulrik Trung N. Tran

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.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. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions.In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43).In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.

Attendance

10.1111/all.15711

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Citations (14)

Faculty Opinions recommendation of Decrease in mortality in severe community-acquired pneumococcal pneumonia: impact of improving antibiotic strategies (2000-2013).

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2014)

César Picado Luis Pérez de Llano

Pneumococcal pneumonia

10.3410/f.718218587.793499383

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Analysis of comorbidities and multimorbidity in adult patients in the International Severe Asthma Registry

Annals of Allergy Asthma & Immunology (2023)

Ghislaine Scélo Carlos A. Torres‐Duque Jorge Máspero Trung N. Tran Ruth Murray

BackgroundInvestigation for the presence of asthma comorbidities is recommended by GINA as their presence can complicate asthma management.ObjectiveTo understand the prevalence and pattern of comorbidities and multimorbidity in adults with severe asthma and their association with asthma-related outcomes.MethodsThis was a cross-sectional study using data from the International Severe Asthma Registry from 22 countries. Thirty comorbidities were identified and categorized a priori as either (1) potentially T2-related, (2) potentially oral corticosteroid (OCS)-related or (3) mimicking/aggravating asthma. The association between comorbidities and asthma-related outcomes was investigated using multivariable models adjusted for country, age at enrollment, and sex.ResultsOf 11,821 patients, 69%, 67%, and 55% had ≥1 potentially T2-related, potentially OCS-related, or mimicking/aggravating comorbidities, respectively; 57% had ≥3 comorbidities, and 33% had comorbidities in all three categories. Patients with allergic rhinitis (AR), nasal polyposis (NP), and chronic rhinosinusitis (CRS) experienced 1.12- (p=0.003), 1.16- (p<0.001) and 1.29-times (p<0.001) more exacerbations/year, respectively, than those without. Patients with NP and CRS were 40% and 46% more likely (p<0.001), respectively, to have received long-term (LT) OCS. All assessed potential OCS-related comorbidities (except obesity) were associated with greater likelihood of LTOCS use (ORs: 1.23-2.77) and, except for dyslipidemia, with greater likelihood of uncontrolled asthma (ORs: 1.29-1.68). All mimicking/aggravating comorbidities assessed were associated with more exacerbations (1.24-1.68 times more), all (except bronchiectasis) with increased likelihood of uncontrolled asthma (ORs: 1.57-1.81) and all (except COPD) with increased likelihood of LTOCS use (ORs: 1.37-1.57). Greater number of comorbidities was associated with worse outcome.ConclusionIn a global study, comorbidity or multimorbidity is reported in most adults with severe asthma and is associated with poorer asthma-related outcomes.

Nasal Polyps

Dyslipidemia

10.1016/j.anai.2023.08.021

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Citations (17)

Biologic Utilization Patterns: Data from the International Severe Asthma Registry (ISAR)

Andrew Menzies‐Gow Eileen Wang Mari-Anne Rowlands Marianna Alacqua Mona Al‐Ahmad

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a7739

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Citations (1)

Risk Stratification in Chronic Obstructive Pulmonary Disease: Can the Spanish Guidelines be Improved?

Archivos de Bronconeumología (2018)