Long-Term Eosinophil Depletion: A Real-World Perspective on the Safety and Durability of Benralizumab Treatment in Severe Eosinophilic Asthma

<b>Background/Objectives:</b> Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody that induces the near-complete depletion of eosinophils. This study aimed to evaluate the long-term safety and effectiveness of benralizumab in patients with severe eosinophilic asthma (SEA) over an extended 48-month follow-up period, offering one of the longest real-world perspectives available. <b>Methods:</b> This was a single-arm, retrospective, observational, multicenter study involving 123 SEA patients treated with benralizumab at a dosage of 30 mg every 4 weeks for the first 3 doses and then every 8 weeks. The safety endpoints focused on the frequency and nature of adverse events and the likelihood that they were induced by benralizumab. The efficacy endpoints focused on lung function, asthma exacerbations and control, and oral corticosteroid use. <b>Results:</b> Benralizumab, consistent with its mechanism of action, led to the rapid and nearly complete depletion of eosinophils. In total, 26 adverse events (21.1%) were observed, with 1.6% related to the treatment and 0.8% categorized as serious (vagal hypotension). Bronchitis was the most common unrelated adverse event (15.4%), occurring between months 36 and 38. Importantly, benralizumab effectiveness and safety were maintained consistently across the 48-month duration, resulting in significant improvements in lung function and reductions in oral corticosteroid use and exacerbation frequency. <b>Conclusions:</b> Benralizumab demonstrated a favorable safety profile, comparable to previously published studies, with perdurable effectiveness in controlling SEA and reducing oral corticosteroid use. Finally, this study provides evidence that near-complete eosinophil depletion does not increase long-term safety risks and supports benralizumab as a reliable treatment option for SEA patients.