What treatment options are available for a patient with asthma and an elevated absolute eosinophil count (Eosinophilia)?

Treatment for Asthma with Absolute Eosinophil Count of 750 cells/μL

For a patient with asthma and an absolute eosinophil count of 750 cells/μL, optimize standard inhaled corticosteroid (ICS) and long-acting β2-agonist (LABA) therapy first; if the patient has severe uncontrolled disease despite high-dose ICS/LABA with ≥2 exacerbations in the past year requiring systemic corticosteroids, add mepolizumab or benralizumab as biologic therapy. 1, 2

Initial Treatment Approach

Standard Controller Optimization

• Begin with high-dose inhaled corticosteroids combined with long-acting β2-agonists as the foundation of therapy for eosinophilic asthma (eosinophil count ≥300 cells/μL qualifies as eosinophilic phenotype). 3, 1
• This eosinophil count of 750 cells/μL clearly indicates type 2 inflammatory asthma and suggests potential benefit from anti-IL-5 therapy if disease remains uncontrolled. 1, 2

Criteria for Adding Biologic Therapy

When to Escalate to Anti-IL-5 Agents

Add biologic therapy when the patient meets all of the following criteria:

• Severe asthma requiring medium to high-dose ICS/LABA 2
• Poor disease control defined as either:
  • ≥2 exacerbations requiring systemic corticosteroids in the preceding 12 months, OR
  • Asthma Control Questionnaire (ACQ) score ≥1.5 2
• Blood eosinophil count ≥300 cells/μL (this patient at 750 cells/μL clearly qualifies) 1, 2

Biologic Agent Selection

First-Line Anti-IL-5 Options

For patients with high eosinophils (≥300 cells/μL), mepolizumab and benralizumab are both appropriate first-line choices, with the following considerations: 1, 2

Mepolizumab (Anti-IL-5 Antibody)

• Dosing: 100 mg subcutaneously every 4 weeks (FDA-approved dose for severe eosinophilic asthma) 4, 5
• Expected outcomes: Approximately 50% reduction in exacerbation rates in patients with severe eosinophilic asthma 2, 5
• Eosinophil reduction: Significantly reduces blood eosinophils but does not achieve complete depletion (31% of patients reach undetectable levels) 6
• Safety profile: No excess serious adverse events; well-tolerated with low discontinuation rates 2

Benralizumab (Anti-IL-5 Receptor Alpha Antibody)

• Dosing: 30 mg subcutaneously every 4 weeks for first 3 doses, then every 8 weeks thereafter 7, 2
• Expected outcomes: Similar ~50% reduction in exacerbation rates 2
• Eosinophil reduction: Achieves complete eosinophil depletion (100% of patients reach undetectable levels within 24 hours) 8, 6
• Safety profile: Generally safe but slightly higher discontinuation rate than mepolizumab (2.3% vs <1%), though absolute numbers remain small 2

Practical Selection Between Agents

Choose mepolizumab over benralizumab if:

• Patient prefers monthly dosing throughout treatment 4
• Concern exists about complete eosinophil depletion 6

Choose benralizumab over mepolizumab if:

• Patient prefers less frequent dosing after initial loading (every 8 weeks vs every 4 weeks) 7, 2
• Rapid and complete eosinophil depletion is desired 8, 6

Expected Clinical Benefits

Efficacy Outcomes with Anti-IL-5 Therapy

• Exacerbation reduction: Approximately 50% decrease in clinically significant exacerbations (requiring ≥3 days of systemic corticosteroids) 2, 5
• Quality of life: Modest improvements in validated scores (ACQ, AQLQ), though may not exceed minimum clinically important difference 2
• Lung function: Small but statistically significant improvement in pre-bronchodilator FEV1 (0.08-0.11 L increase) 2
• Oral corticosteroid sparing: Significant reduction in maintenance oral corticosteroid requirements 3

Important Clinical Caveats

Common Pitfalls to Avoid

• Do not use anti-IL-5 therapy as monotherapy: These agents are add-on treatments and require continuation of optimized inhaled therapy 3, 2
• Ensure adequate trial of standard therapy first: Anti-IL-5 agents are indicated only after failure of high-dose ICS/LABA, not as initial treatment 2
• Monitor for treatment response: Assess clinical improvement (exacerbation frequency, symptom control) rather than relying solely on eosinophil counts 1, 2
• Consider non-eosinophilic causes: If patient fails to respond to anti-IL-5 therapy, re-evaluate diagnosis and consider alternative phenotypes or comorbidities 3

Safety Monitoring

• Mepolizumab: Monitor for hypersensitivity reactions; no routine laboratory monitoring required beyond clinical assessment 4, 2
• Benralizumab: Monitor for injection site reactions, worsening asthma, and nasopharyngitis; blood eosinophil reduction occurs within 24 hours and is maintained throughout treatment 8, 7
• Both agents: No increased risk of serious adverse events compared to placebo 2

Alternative Considerations

If Anti-IL-5 Therapy Fails or Is Contraindicated

• Dupilumab (anti-IL-4 receptor alpha) may be considered as it demonstrates superior exacerbation reduction in some studies for patients with eosinophils ≥300 cells/μL 1
• Omalizumab (anti-IgE) is preferred only if patient has allergy-driven asthma with lower eosinophil counts (150-299 cells/μL) or elevated IgE, which is not the primary indication for this patient with eosinophils of 750 cells/μL 1

Special Populations

• Pediatric patients 6-11 years: Benralizumab dosing is weight-based (10 mg for <35 kg, 30 mg for ≥35 kg); mepolizumab is also approved for ages ≥6 years 7, 4
• Adolescents 12-17 years: Same dosing as adults for both agents 7
• Pregnancy: Limited data available; both agents are IgG antibodies that cross the placenta, but no evidence of fetal harm in animal studies 7