What is the dosing regimen and indications for Benralizumab (anti-interleukin-5 receptor alpha subunit monoclonal antibody) in patients with severe asthma or hypereosinophilic syndrome?

Benralizumab Dosing and Indications

Benralizumab is administered at 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter, and is indicated for severe eosinophilic asthma uncontrolled on high-dose inhaled corticosteroids plus long-acting beta-agonists, and for eosinophilic granulomatosis with polyangiitis (EGPA). 1

Primary Indications

Severe Eosinophilic Asthma

• Benralizumab is specifically indicated for patients aged 12 years and older with severe asthma and an eosinophilic phenotype (blood eosinophils ≥300 cells/μL) whose disease remains uncontrolled despite treatment with high-dose inhaled corticosteroids plus long-acting β2-agonists 2, 1, 3

• The medication works by binding to the IL-5 receptor alpha subunit on eosinophils and basophils, inducing rapid and nearly complete eosinophil depletion through antibody-dependent cell-mediated cytotoxicity (ADCC) 1

• Eosinophil depletion occurs within 24 hours of the first dose, with median blood eosinophil counts reaching 0 cells/μL by 4 weeks and maintained throughout treatment 1, 4

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• The American College of Rheumatology recommends benralizumab for adult patients with EGPA, particularly those with refractory asthma or ENT disease without systemic manifestations despite high-dose glucocorticoids and optimized inhaled therapy 5

• The same dosing regimen applies: 30 mg subcutaneously every 4 weeks for 3 doses, then every 8 weeks 5, 1

Standard Dosing Regimen

Administration Schedule

• Loading phase: 30 mg subcutaneously every 4 weeks for the first 3 doses 1, 3
• Maintenance phase: 30 mg subcutaneously every 8 weeks thereafter 1, 3

Injection Sites and Training

• Administer subcutaneously in the abdomen, thigh, or upper arm using an auto-injector or pre-filled syringe 2
• The first 2 injections should be administered in a hospital setting for training purposes and to monitor for the minimal risk of anaphylaxis 2
• Self-injection at home is possible after initial training 2

Clinical Efficacy Outcomes

Asthma Exacerbation Reduction

• In patients with blood eosinophils ≥300 cells/μL, benralizumab reduced annual exacerbation rates by 36% (Q4W regimen) and 28% (Q8W regimen) compared to placebo 3
• Another pivotal trial demonstrated even greater reductions: 45% (Q4W) and 51% (Q8W) versus placebo 6

Lung Function and Symptom Improvement

• Benralizumab significantly improved pre-bronchodilator FEV1 at 48 weeks with both dosing regimens 3, 6
• Total asthma symptom scores improved significantly with the Q8W regimen 3, 6
• Oral corticosteroid use was substantially reduced in treated patients 4, 7

Long-Term Safety and Durability

• Real-world data over 48 months demonstrates maintained effectiveness with a favorable safety profile 4
• Near-complete eosinophil depletion does not increase long-term safety risks 4

Biologic Selection Algorithm for Severe Asthma

When choosing among biologics for severe asthma, consider the following framework 2:

• Eosinophilic asthma (blood eosinophils ≥300 cells/μL): Benralizumab, mepolizumab, or reslizumab 2
• Highly eosinophilic asthma with chronic rhinosinusitis with nasal polyps: Consider mepolizumab first 2
• Type 2 asthma (broader phenotype): Dupilumab or tezepelumab 2
• Allergy-driven asthma: Omalizumab 2
• Females planning pregnancy: Omalizumab (preferred due to more safety data) 2

Off-Label and Emerging Indications

Hypereosinophilic Syndrome

• Benralizumab demonstrated significant lowering of eosinophil counts in both serum and tissue, with 74% of patients achieving sustained response at 48 weeks 8, 5
• No adverse events limited treatment in these patients 8

Allergic Bronchopulmonary Aspergillosis (ABPA)

• The European Respiratory Society recommends benralizumab as an option for managing treatment-dependent ABPA 5

Eosinophilic Esophagitis (EoE)

• The American Gastroenterological Association does NOT currently recommend benralizumab as first-line therapy for EoE, suggesting its use only in clinical trials 8
• However, case reports show potential efficacy with complete resolution of dysphagia and histological remission in patients with both eosinophilic asthma and EoE 5

Safety Profile and Adverse Events

Common Adverse Events

• Most common adverse events include worsening asthma, nasopharyngitis, and injection site reactions 8, 3, 6
• Bronchitis occurred in 15.4% of patients in long-term follow-up, typically between months 36-38 4
• Treatment-related adverse events are rare (1.6%), with serious adverse events occurring in only 0.8% of patients 4

Monitoring Recommendations

• The European Respiratory Society recommends therapeutic drug monitoring when using benralizumab 8, 5
• Blood eosinophil counts should be monitored to confirm therapeutic response 1

Important Clinical Considerations

Switching from Other Biologics

• Benralizumab can be effective in patients who have failed other biologics, including omalizumab and mepolizumab 7
• For EGPA patients, benralizumab can be considered when disease is refractory to mepolizumab therapy 5

Onset of Action

• Clinical improvement may take weeks to months, though eosinophil depletion occurs within 24 hours 2, 1
• Patients should be counseled about this timeline to maintain adherence during the initial treatment period 2

Basophil Depletion

• Treatment also results in significant reductions in blood basophils, which is consistently observed across all clinical studies 1