Cumulative corticosteroid burden over 25 years in patients initiating biologic therapy for severe asthma: a nationwide cohort study.

Background: Systemic corticosteroid use in severe asthma is associated with morbidity and mortality. Little is known about the long-term corticosteroid burden prior to biologic therapy. This study aims to estimate the cumulative corticosteroid burden in patients initiating biologic therapy and impact of pre-biologic disease trajectories on corticosteroid burden. Methods: Patients in the Danish Severe Asthma Register initiating biologic therapy between 2016 and 2022 had their redemptions of inhaled, nasal and systemic corticosteroids from 1995 until first administration of biologic therapy retrieved. Prednisolone-equivalent doses were calculated for all redeemed corticosteroids, presented as either cumulative or daily exposure. Results: A total of 542 patients (median follow-up 16 years) were included. Prior to biologic initiation, the median (IQR) total corticosteroid burden during follow-up was 17.1 g (8.4-36.2) of which 7.2 g (3.3-16.3) were systemic corticosteroids. 56.3% of patients were exposed to more systemic than inhaled corticosteroids. Two-thirds of patients experienced a corticosteroid exposure ≥5 mg prednisolone equivalents daily in the year prior to biologic therapy. Additionally, 10% had inhaled corticosteroid exposure ≥5 mg daily prednisolone equivalents for over two decades. Cumulative exposure was highest in chronic severe asthma patients compared to those with gradual- or recent-onset severe asthma. 72% (12.4 g (3.9-34.2)) of total corticosteroid exposure occurred prior to the first registered specialist visit. Conclusion: Patients with severe asthma have substantial cumulative corticosteroid exposure prior to biologic therapy, with the majority occurring prior to specialist assessment. Exposure reduction is a key priority to minimise corticosteroid exposure-related comorbidities.