Integrated Safety and Efficacy Among Patients Receiving Benralizumab for Up to Five Years.

BACKGROUND: Benralizumab is an IL-5Rα-directed monoclonal antibody indicated for patients with severe, uncontrolled eosinophilic asthma.

OBJECTIVE: To evaluate the long-term safety and tolerability of benralizumab among adults treated for up to 5 years.

METHODS: This analysis included adults treated with placebo or subcutaneous benralizumab 30 mg every 4 or 8 weeks in the 48-week SIROCCO, 56-week CALIMA, and 28-week ZONDA pivotal trials, who were subsequently enrolled in the 56-week double-blind BORA extension and continued assigned regimens or initiated benralizumab (if previously on placebo) for 16 to 40 weeks, before entering the open-label MELTEMI extension. Safety was measured by adverse and serious adverse event rates. Exacerbations were evaluated in patients with blood eosinophils ≥300 cells/μL receiving high-dose inhaled corticosteroids (bEOS ≥300 cells/μL-HDICS) at baseline.

RESULTS: Overall, 446 received treatment and 384 (86.1%) completed the study; 157 (35.2%) received benralizumab for ≥4 years. Adverse and serious adverse event rates (28.5-32.4 and 6.3-8.4 per 100 patient years, respectively) were low, stable over time, and did not increase with exposure; few (n=8) discontinued due to adverse events. Serious infections and hypersensitivity event rates were consistent with previous studies. Among patients with bEOS ≥300 cells/μL-HDICS receiving benralizumab every 8 weeks, at least 75% had zero exacerbations annually during the integrated analysis period.

CONCLUSION: In patients with severe, uncontrolled eosinophilic asthma, long-term benralizumab was safe and well tolerated for up to 5 years. There were no new safety signals, and exacerbations were eliminated in similar percentages of patients as in predecessor studies.