Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics

Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. To compare the risk of developing new-onset OCS-related adverse outcomes between biologic-initiators and non-initiators. This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; UK). For biologic-initiators, the index date was the date of biologic-initiation. For non-initiators, it was the date of enrolment (for ISAR) or a random medical appointment date (for OPCRD). Inverse-probability-of-treatment-weighting was used to improve comparability between groups and weighted Cox proportional hazard models were used to estimate the hazard ratios (HR) of developing OCS-related adverse outcomes for up to five years from the index date. 42,908 patients were included. Overall, 27.3% and 4.7% of biologic-initiators and non-initiators were long-term OCS users (daily intake ≥90 consecutive days in year pre-index), with a mean prednisolone-equivalent daily dose of 10.2 mg and 6.2 mg, respectively. Compared to non-initiators, biologic-initiators had decreased rate of developing any OCS-related adverse outcome (HR [95% CI]: 0.82 [0.72-0.93]; p=0.002), primarily driven by reduced rate of developing diabetes (0.62 [0.45-0.87]; p=0.006]), major cardiovascular events (0.65 [0.44-0.97]; p=0.034), and anxiety/depression (0.68 [0.55-0.85]; p=0.001]). There were no significant differences in the rates of new-onset cataract (HR: 0.77 [95% CI: 0.47-1.25]), sleep apnea (HR: 0.82 [95% CI: 0.78-1.41]), or other OCS-related AOs assessed (e.g. osteoporosis). The results were consistent across both datasets. Our findings highlight the role for biologics in preventing new-onset OCS-related adverse outcomes in patients with severe asthma.