Mortality Among Adults with Subspecialist-Treated Severe Asthma: A Descriptive Analysis from the Observational CHRONICLE Study

Njira L Lugogo,1 Jennifer Trevor,2 Joseph D Spahn,3 Reynold A Panettieri Jr,4 Donna D Carstens,3 Christopher S Ambrose5 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA; 2Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; 3BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 4Rutgers Institute for Translational Medicine and Science, The State University of New Jersey, New Brunswick, NJ, USA; 5BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USACorrespondence: Christopher S Ambrose, BioPharmaceuticals Medical, AstraZeneca, One Medimmune Way, Gaithersburg, MD, 20878, USA, Tel +1 301-398-4454, Email [email protected]: There are limited recent data assessing all-cause mortality for US patients with severe asthma. This descriptive analysis evaluated all-cause mortality in a real-world cohort of US adults with subspecialist-treated severe asthma, examining patient characteristics among those who died, physician-reported primary causes of death, and associations with treatment class.Patients and Methods: CHRONICLE (NCT03373045) was an observational study of US adults (aged ≥ 18 years) with subspecialist-treated severe asthma, enrolled from February 2018 to October 2024. Patients met at least one of the following criteria: ongoing FDA-approved monoclonal antibody therapy, maintenance systemic corticosteroids (mSCS) for ≥ 50% of the prior year, or persistently uncontrolled asthma despite high-dosage inhaled corticosteroids and additional controllers. All-cause mortality was assessed descriptively, overall and by treatment class at time of death. Investigators reported primary causes of death and COVID-19 involvement. Treatment class exposure was calculated by the cumulative days on biologics and/or mSCS.Results: Among 4366 enrolled patients, mean age was 54.7 years; 69.7% were female, 73.1% were White, and 18.6% were Black. Over 14,758 person-years of observation, 130 deaths occurred (3.0%), yielding a mortality of 8.8 (95% confidence interval: 7.4, 10.5) per 1000 person-years. Cardiovascular disease was the leading cause of death (25.4%), followed by cancer (13.1%) and asthma (1.5%). COVID-19 contributed to 8.5% of deaths. Observed associations for all-cause mortality ranged from 6.8 per 1000 person-years in patients who were receiving biologics without mSCS to 31.6 per 1000 person-years in those receiving mSCS without biologics.Conclusion: US adults with subspecialist-treated severe asthma have an increased risk of all-cause mortality, especially those patients receiving mSCS. These findings highlight the importance of identifying mortality risks and limiting the use of mSCS whenever possible while supporting further research into the relationship between severe asthma and cardiovascular disease.Keywords: asthma, death, mortality, observational study, severe