What is the comparative efficacy and safety of dupilumab (dupilumab) vs anti-IL-5 agents (mepolizumab, benralizumab) and anti-IgE (omalizumab) in asthma?

Comparative Efficacy and Safety of Dupilumab vs Anti-IL-5 and Anti-IgE Biologics in Asthma

For patients with eosinophils ≥300 cells/μL, dupilumab and mepolizumab demonstrate superior exacerbation reduction compared to benralizumab, while for patients with eosinophils 150-299 cells/μL or allergy-driven asthma, omalizumab may be preferred over anti-IL-5 agents. 1, 2

Efficacy in High Eosinophil Populations (≥300 cells/μL)

Exacerbation Reduction

• Dupilumab reduces exacerbations by 68% (RR 0.32; 95% CI 0.23-0.45) compared to placebo 2
• Mepolizumab reduces exacerbations by 63% (RR 0.37; 95% CI 0.30-0.45) 2
• Benralizumab reduces exacerbations by 51% (RR 0.49; 95% CI 0.43-0.55) 2
• In patients with eosinophils ≥300/μL, anti-IL-5 biologics demonstrated fewer exacerbations than dupilumab (weighted RR 2.85; 95% CI 1.82-4.46 for dupilumab vs anti-IL-5) 3

Lung Function Improvement (FEV1)

• Dupilumab improves FEV1 by 230 mL (95% CI 160-300 mL) at week 12 2, 4
• Benralizumab improves FEV1 by 150 mL (95% CI 100-200 mL) 2
• Mepolizumab improves FEV1 by 150 mL (95% CI 66-220 mL) 2

Asthma Control

• Mepolizumab provides greatest ACQ improvement (MD -0.63; 95% CI -0.81 to -0.45) 2
• Dupilumab shows moderate ACQ improvement (MD -0.48; 95% CI -0.83 to -0.14) 2
• Benralizumab demonstrates smallest ACQ improvement (MD -0.32; 95% CI -0.43 to -0.21) 2

Efficacy in Moderate Eosinophil Populations (150-299 cells/μL)

• Benralizumab reduces exacerbations by 38% (RR 0.62; 95% CI 0.52-0.73) and improves FEV1 by 81 mL (95% CI 8-150 mL) 2
• Dupilumab reduces exacerbations by 40% (RR 0.60; 95% CI 0.38-0.95) but FEV1 improvement was not statistically significant in this subgroup 2
• Mepolizumab data in this eosinophil range showed limited efficacy 2

Efficacy in Low Eosinophil Populations (<300 cells/μL)

• Omalizumab demonstrated 68% reduction in hospitalizations compared to anti-IL-5 agents (weighted RR 0.32; 95% CI 0.13-0.51) in patients with eosinophils <300/μL 3
• This makes omalizumab the preferred choice for allergy-driven asthma with lower eosinophil counts 1

Safety Profile Comparison

Serious Adverse Events

• Mepolizumab shows lowest odds of serious adverse events (OR 0.67; 95% CI 0.48-0.92) 2
• Benralizumab demonstrates favorable safety (OR 0.74; 95% CI 0.59-0.93) with 74% sustained response at 48 weeks and no treatment-limiting adverse events 5, 6
• Dupilumab shows no significant difference from placebo in serious adverse events (OR 1.0; 95% CI 0.74-1.4) 2
• Omalizumab requires monitoring for anaphylaxis risk 1

Common Adverse Events

• Dupilumab: Injection site reactions (35%), nasopharyngitis (17%), and hypereosinophilia in 4.1% of patients 1, 4
• Benralizumab: Worsening asthma, nasopharyngitis, injection site reactions, with significant eosinophil reduction within 24 hours 5
• Mepolizumab: Generally well-tolerated with mild injection site reactions 1

Clinical Decision Algorithm Based on Guidelines

The 2025 EUFOREA guidelines provide the following selection framework: 1

1. Type 2 asthma with high eosinophils (≥300 cells/μL): Mepolizumab, reslizumab, or benralizumab
2. Type 2 asthma (broader phenotype): Dupilumab or tezepelumab
3. Allergy-driven asthma: Omalizumab
4. Females planning pregnancy: Omalizumab (first choice)
5. Comorbid CRSwNP: Dupilumab (first choice) or mepolizumab if highly eosinophilic asthma present

Important Clinical Considerations

Phenotype-Specific Targeting

• The 2011 guidelines emphasize that anti-IL-5 therapy is most effective when patients are selected based on failure to control eosinophilia with high-dose oral corticosteroids, achieving 50% reduction in exacerbations in this steroid-refractory population 1
• Approximately 50% of asthmatic patients have TH2-low asthma, where type 2-targeted biologics may be less effective 1

Biomarker Monitoring

• Dupilumab reduces FeNO by 35% at week 2 and total IgE by 52-70% over 24-52 weeks 7, 8
• Benralizumab produces rapid eosinophil depletion within 24 hours, maintained throughout treatment 5, 9
• Anti-drug antibodies occur in 13% of dupilumab-treated patients and 9% of benralizumab-treated patients, potentially affecting efficacy 9, 7

Oral Corticosteroid Sparing

• All three biologics (dupilumab, mepolizumab, benralizumab) enable reduction in OCS maintenance doses without compromising asthma control 8, 4
• This represents a critical benefit for reducing long-term corticosteroid-related morbidity 8

Key Pitfall to Avoid

The most common error is failing to phenotype patients appropriately before biologic selection—using anti-IL-5 agents in low-eosinophil, allergy-driven asthma or omalizumab in high-eosinophil, non-allergic asthma will result in suboptimal outcomes 1, 3. Blood eosinophil count and allergy testing should guide initial biologic choice, with the understanding that minimal clinically important differences exist between agents when appropriately matched to phenotype 2.