Impact of Biologic Initiation on New-onset of Corticosteroid-related Adverse Effects in Patients With Severe Asthma

Abstract RATIONALE: Use of oral corticosteroids (OCS), both as maintenance treatment and for exacerbations, is associated with serious adverse effects (AEs). Biologic use decreases the need for OCS in patients with severe asthma and therefore could reduce the risk of OCS-related AEs. Exploring this relationship could inform treatment decisions and highlight the benefits of biologics beyond asthma control. METHODS: Longitudinal data from adult patients with severe asthma were pooled from two real-world data sources: the International Severe Asthma Registry (ISAR, 16 countries) and the Optimum Patient Care Research Database (OPCRD, the United Kingdom). For biologic initiators, the index date was date of biologic initiation. For non-initiators, the index date was the date of enrollment into the registry for ISAR and a random medical appointment date for OPCRD. Index dates and end of follow-up spanned from 2008 to 2024. We compared the risk of developing type-2 diabetes mellitus, a major cardiovascular event (heart failure, myocardial infarction, or cerebrovascular accident), sleep apnea, pulmonary embolism, anxiety/depression, osteoporosis, renal failure, peptic ulcer, cataract, glaucoma, and pneumonia between biologic initiators and non-initiators. Time at risk was censored at 5 years. We used inverse probability for treatment weighting to improve the balance between comparison groups for potential confounders. Weighted Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of being diagnosed with new-onset OCS-related AEs. RESULTS: The study population included 5,690 biologic initiators and 37,218 non-initiators, followed for a median of 2.1 years (interquartile range: 1.0-3.9). The proportions of long-term OCS users (daily intake for ≥90 consecutive days in the year preceding index date) were 27.3% and 4.7% in biologic initiators and non-initiators, with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. The risk of any AE was lower in biologic initiators than in non-initiators (HR=0.82, 95% CI: 0.72-0.93) (Figure). This overall risk reduction was mainly driven by a reduction in the risk of diabetes (HR=0.62, 0.45-0.87), major cardiovascular events (HR=0.65, 0.44-0.97), and anxiety/depression (HR=0.68, 0.55-0.85). We did not detect an association between initiating biologics and the risk of osteoporosis (HR=0.96, 0.65-1.42), sleep apnea (HR=0.82, 0.58-1.15), pneumonia (HR=1.05, 0.78-1.40), or less frequent AEs included in our analysis (renal failure, peptic ulcer, cataract, and glaucoma). CONCLUSIONS: Initiation of biologics in patients with severe asthma was associated with reduction in their risk of new-onset OCS-related AEs, including diabetes, anxiety/depression, and major cardiovascular events.