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

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 Registry initiating biologic therapy between 2016-2022 were included and followed retrospectively in prescription databases starting 1995. We performed sequence analysis for inhaled corticosteroid (ICS) 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%), 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 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 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.