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

<b>Rationale:</b> 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. <b>Objective:</b> To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. <b>Methods:</b> 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). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. <b>Measurements and Main Results:</b> A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; <i>P</i> = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; <i>P</i> = 0.006), major cardiovascular events (0.65 [0.44-0.97]; <i>P</i> = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; <i>P</i> = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. <b>Conclusions:</b> Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

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Publication Details

Journal
American Journal of Respiratory and Critical Care Medicine
Published
2025-06-13
DOI
https://doi.org/10.1164/rccm.202501-0246oc
Citations
13
Primary Topic
Asthma and respiratory diseases
Type
article
Field-Weighted Citation Impact
15.14
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article

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

Lakmini Bulathsinhala, Piotr Kuna, Matthew Peters, Guy Brusselle et al.
13 citations
American Journal of Respiratory and Critical Care Medicine
Asthma and respiratory diseases
15.14
article

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

Lakmini Bulathsinhala, Piotr Kuna, Matthew Peters, Guy Brusselle, Riyad Al‐Lehebi, Martín Sívori, Mariko Siyue Koh, Tatsuya Nagano, Andriana Ι. Papaioannou, Liam Gabriel Heaney, Mohit Bhutani, Konstantinos Exarchos, Benjamin Emmanuel, Wenjia Chen, Ruth Murray, Njira Lucia Lugogo, Athena Gogali, Sinthia Bosnic‐Anticevich, Chau‐Chyun Sheu, Kirsty Fletton, Andrew Menzies‐Gow, Florence Schleich, Mohsen Sadatsafavi, Hao‐Chien Wang, Trung N. Tran, Cathy Emmas, Michael P. Makris, Jorge Fernando Maspero, Flavia Hoyte, Giorgio Walter Canonica, Eve Denton, Chin Kook Rhee, Libardo Jiménez-Maldonado, Delbert R. Dorscheid, John Busby, Michael E. Wechsler, George Christoff, Désirée Larenas‐Linnemann, John Townend, Peter G. Gibson, Todor A. Popov, ARNAUD AB BOURDIN, Francesca Puggioni, Peter G. Middleton, Ghislaine Scélo, Alan Altraja, Eileen Wang, David Price, Susanne Hansen, Paul Pfeffer, Laila Salameh, Céline Bergeron, Κonstantinos Κostikas, Victoria Carter, Andréanne Côté, Patrick Mitchell, Borja G. Cosío, Mona Al‐Ahmad, Carlos A. Torres‐Duque, Simon Couillard, Neda Stjepanovic, Yuji Tohda, Rohit Katial, Enrico Marco Heffler, Belinda Cochrane, Ming‐Ju Tsai, Luis Pérez de Llano, Celeste Porsbjerg, Adeeb A. Bulkhi, Takashi Iwanaga, Iván Solarte, Roy A. Pleasants, Cláudia Chaves Loureiro, Mark Hew, Aaron Beastall, Yah Ru Juang, Anqi Liu, Pujan H. Patel, David J. Jackson, Christine Jenkins, Bassam Mahboub, Diahn‐Warng Perng, Bernt Bøgvald Aarli, Kenneth R. Chapman, Renaud Louis, Ledit Ardusso, Nevaashni Eleangovan, Charlotte Suppli Ulrik
article en
13 citations

Abstract

<b>Rationale:</b> 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. <b>Objective:</b> To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. <b>Methods:</b> 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). For biologic initiators, the index date was the date of biologic initiation. For noninitiators, it was the date of enrollment (for ISAR) or a random medical appointment date (for OPCRD). Inverse probability of treatment weighting was used to improve comparability between groups, and weighted Cox proportional hazard models were used to estimate the hazard ratios (HRs) of developing OCS-related adverse outcomes for up to 5 years from the index date. <b>Measurements and Main Results:</b> A total of 42,908 patients were included. Overall, 27.3% and 4.7% of biologic initiators and noninitiators were long-term OCS users (daily intake ⩾90 consecutive days in year before the index date), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared with noninitiators, biologic initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% confidence interval (CI)]: 0.82 [0.72-0.93]; <i>P</i> = 0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; <i>P</i> = 0.006), major cardiovascular events (0.65 [0.44-0.97]; <i>P</i> = 0.034), and anxiety and/or depression (0.68 [0.55-0.85]; <i>P</i> = 0.001). There were no significant differences in the rates of new-onset cataract (HR, 0.77 [95% CI, 0.47-1.25]), sleep apnea (HR, 0.82 [95% CI, 0.78-1.41]), or other OCS-related adverse outcomes assessed (e.g., osteoporosis). The results were consistent across both datasets. <b>Conclusions:</b> Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.

American Journal of Respiratory and Critical Care MedicineVol. 211(7)
AstraZeneca (United Kingdom) (GB), University of North Carolina at Chapel Hill (US), Queen's University Belfast (GB), Camden and Campbelltown Hospitals (AU), Centre National de la Recherche Scientifique (FR), Humanitas University (IT), Alfaisal University (SA), Université de Sherbrooke (CA), University of Ulster (GB), University of British Columbia (CA), National Yang Ming Chiao Tung University (TW), Kaohsiung Medical University (TW), University of Alberta (CA), Inserm (FR), Universidad de La Sabana (CO), University of Liège (BE), National University of Singapore (SG), Queen Mary University of London (GB), National Taiwan University (TW), King's College London (GB), University of Toronto (CA), University of Ioannina (GR), University of Aberdeen (GB), Université de Montpellier (FR), Umm al-Qura University (SA), Universidade de Santiago de Compostela (ES), National and Kapodistrian University of Athens (GR), Trinity College Dublin (IE), Singapore General Hospital (SG), Barts Health NHS Trust (GB), Pontificia Universidad Javeriana (CO), Universidad de Buenos Aires (AR), University of Michigan (US), Vancouver Hospital and Health Sciences Centre (CA), Concord Repatriation General Hospital (AU), John Hunter Hospital (AU), Haukeland University Hospital (NO), Rashid Hospital (AE), Woolcock Institute of Medical Research (AU), Frederiksberg Hospital (DK), Arthritis Australia (AU), Ghent University Hospital (BE), King Fahd Medical City (SA), Bispebjerg Hospital (DK), Hvidovre Hospital (DK), Erasmus MC (NL), Hospitais da Universidade de Coimbra (PT), Tartu University Hospital (EE), Copenhagen University Hospital (DK), Kaohsiung Medical University Chung-Ho Memorial Hospital (TW), Harefield Hospital (GB), Vancouver General Hospital (CA), Taipei Veterans General Hospital (TW), Westmead Hospital (AU), University of Sharjah (AE), Medical University of Sofia (BG), National Jewish Health (US), University of Cundinamarca (CO), UNSW Sydney (AU), Kuwait University (KW), National University of Rosario (AR), Hunter Medical Research Institute (AU), The Centre for Health (New Zealand) (NZ), Care UK (United Kingdom) (GB), Center for Clinical Research and Prevention (DK), Centre Hospitalier Universitaire de Montpellier (FR), Kindai University Hospital (JP), Royal Brompton Hospital (GB), Lung Institute (US), Hospital Médica Sur (MX), Hospital Ramos Mejía (AR), University Hospital St. Ivan Rilski (BG), ENT and Allergy (US), AstraZeneca (Australia) (AU), The George Institute for Global Health (AU), Michigan United (US), Michigan Medicine (US), Laiko General Hospital of Athens (GR), Observational & Pragmatic Research Institute (SG), Fundación Neumológica Colombiana (CO), Monash Health (AU), Medical University of Lodz (PL), Health Research Institute of the Balearic Islands (ES), Ministry of Health (KW), Royal Victoria Hospital (GB), National Taiwan University Hospital (TW), Centre Hospitalier Universitaire de Liège (BE), University of Palermo (AR), Central Clinical Hospital (PL), University General Hospital Attikon (GR), AstraZeneca (Sweden) (SE), Hospital Universitario Lucus Augusti (ES), Capital Region of Denmark (DK), William Harvey Research Institute (GB), National University Health System (SG), AstraZeneca (United States) (US), Physiol (Belgium) (BE), Hospital Universitario Son Espases (ES), Hospital Universitario San Ignacio (CO), Dubai Medical College (AE), Favaloro Foundation (AR), The Catholic University of Korea Seoul St. Mary's Hospital (KR), IRCCS Humanitas Research Hospital (IT), Alfred Health (AU), Université Laval (CA), University of Bergen (NO), University of Tartu (EE), Monash University (AU), Western Sydney University (AU), Kobe University (JP), University of Coimbra (PT), University of Newcastle Australia (AU), Catholic University of Korea (KR), University of Colorado Denver (US), Macquarie University (AU)
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