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. 2025 Apr 3;65(4):2401497.
doi: 10.1183/13993003.01497-2024. Print 2025 Apr.

Pre-biologic disease trajectories are associated with morbidity burden and biologic treatment response in severe asthma

Marianne Baastrup Soendergaard  1   2 , Frederikke Hjortdahl  1   2 , Susanne Hansen  1 , Anne-Sofie Bjerrum  3 , Anna von Bülow  1 , Ole Hilberg  4 , Barbara Bonnesen Bertelsen  5 , Claus Rikard Johnsen  6 , Sofie Lock-Johansson  7 , Roxana Vijdea  8 , Linda Makowska Rasmussen  6 , Johannes Martin Schmid  3 , Charlotte Suppli Ulrik  9 , Celeste Porsbjerg  1 , Kjell Erik Julius Håkansson  10
Affiliations

Pre-biologic disease trajectories are associated with morbidity burden and biologic treatment response in severe asthma

Marianne Baastrup Soendergaard et al. Eur Respir J. .

Abstract

Background: Biologics can induce remission in some patients with severe asthma; however, little is known about pre-biologic disease trajectories and their association with outcomes from biological treatment. We aimed to identify long-term trajectories of disease progression in patients initiating biologics and investigate trajectory associations with disease burden and impact on biologic therapy efficacy.

Methods: Patients in the Danish Severe Asthma Register initiating biologic therapy between 2016 and 2022 were included and followed retrospectively in prescription databases starting 1995. We performed sequence analysis for inhaled corticosteroid treatment intensity over time combined with unsupervised trajectory clustering.

Results: In total, 755 patients were included and three pre-biologic disease trajectories were identified: "Chronic severe asthma" (26%), "Gradual onset severe asthma" (35%) and "Recent, sudden onset severe asthma" (39%). "Chronic severe asthma" patients were older, had the longest disease duration (35 years), the most impaired pulmonary function, the highest comorbidity prevalence and the lowest employment rate. "Recent, sudden onset severe asthma" patients were younger, had shorter disease duration (5 years), more tobacco exposure and the least impaired lung function. "Gradual onset severe asthma" patients had an intermediate burden of disease. The "Chronic severe asthma" cluster demonstrated the lowest prevalence of remission (17%) compared to the "Gradual onset severe asthma" (29%) and "Recent, sudden onset severe asthma" (32%) clusters.

Conclusions: Three pre-biologic disease trajectories were identified, with increased disease duration and activity associating with asthma and comorbidity burden. Early intervention may be key to prevent irreversible adverse outcomes for patients with severe asthma.

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Conflict of interest statement

Conflict of interest: M.B. Soendergaard reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK, AstraZeneca and ALK, and participation on a data safety monitoring board or advisory board with AstraZeneca. F. Hjortdahl reports employment with Novo Nordisk starting September 2024. A-S. Bjerrum reports payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca and GSK. A. von Bülow reports consultancy fees from Novartis DK, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, Novartis and GSK, and participation on a data safety monitoring board or advisory board with AstraZeneca and Novartis. L.M. Rasmussen reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, ALK, GSK and Teva, support for attending meetings from AstraZeneca and Chiesi, and participation on a data safety monitoring board or advisory board with AstraZeneca, Sanofi, GSK and Teva. C.S. Ulrik reports grants from Sanofi, Novartis, Boehringer Ingelheim and AstraZeneca, consultancy fees from Chiesi, Teva, OrionPharma, Menarini, AstraZeneca, Takeda and GSK, payment or honoraria for lectures, presentations, manuscript writing or educational events from Orion Pharma, AstraZeneca and Teva, and participation on a data safety monitoring board or advisory board with Novartis, Sanofi, GSK, Chiesi, AstraZeneca, Boehringer Ingelheim and Pfizer. C. Porsbjerg reports grants from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, consultancy fees from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, payment or honoraria for lectures, presentations, manuscript writing or educational events from AstraZeneca, GSK, Novartis, Teva, Sanofi, Chiesi and ALK, and participation on a data safety monitoring board or advisory board with AstraZeneca, Novartis, Teva, Sanofi and ALK. K.E.J. Håkansson reports grants from Sanofi Genzyme and AstraZeneca, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, GSK, Chiesi, Teva and Sanofi Genzyme. The remaining authors have no potential conflicts of interest to disclose.

Figures

None
Overview of the study. ICS: inhaled corticosteroid; FEV1: forced expiratory volume in 1 s.
FIGURE 1
FIGURE 1
Inclusion flow in a nationwide cohort of 755 patients with severe asthma initiating biologic therapy.
FIGURE 2
FIGURE 2
Clustered long-term inhaled corticosteroid (ICS) treatment trajectories of 755 patients with severe asthma up to 26 years prior to initiating biologic therapy.
FIGURE 3
FIGURE 3
Pre-biologic disease trajectory cluster-stratified prevalence of corticosteroid exposure-associated comorbidities in 755 patients with severe asthma initiating biologic therapy. GORD: gastro-oesophageal reflux disease. p-values represent Chi-squared tests.
FIGURE 4
FIGURE 4
Pre-biologic disease trajectory cluster-stratified a) efficacy of biologic treatment after 12 months and b) individual treatment remission domains after 12 months of treatment in 755 patients with severe asthma initiating biologic therapy. OCS: oral corticosteroid; ACQ: Asthma Control Questionnaire; FEV1: forced expiratory volume in 1 s.
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