What biologics, such as mepolizumab (anti-IL-5 antibody), are used to treat eosinophilic Chronic Obstructive Pulmonary Disease (COPD)?

Biologics for Eosinophilic COPD

Mepolizumab is the most established biologic therapy for eosinophilic COPD, showing a 19% reduction in moderate or severe exacerbations in patients with blood eosinophil counts ≥150 cells/μL, though it does not significantly reduce hospitalization or mortality rates. 1

Current Evidence for Biologics in Eosinophilic COPD

Anti-IL-5 Therapies

1. Mepolizumab (Anti-IL-5)

   • Reduces moderate or severe exacerbations by 19% in patients with eosinophil counts ≥150 cells/μL (high-certainty evidence) 1
   • Most effective in patients with higher blood eosinophil counts (≥300 cells/μL) 2
   • Dosage: 100 mg subcutaneously every 4 weeks 2
   • Does not significantly impact time to readmission or death (recent phase 2b trial) 3

2. Benralizumab (Anti-IL-5 Receptor)

   • Reduces severe exacerbations requiring hospitalization by 37% in patients with eosinophil counts ≥220 cells/μL (100 mg dose, high-certainty evidence) 1
   • Improves pre-bronchodilator FEV1 compared to placebo 4
   • More effective in patients with higher baseline blood eosinophil counts 4

Patient Selection for Biologic Therapy

Biologics should be considered for COPD patients with:

• Persistent eosinophilic inflammation (blood eosinophil count ≥150-300 cells/μL)
• History of moderate to severe exacerbations despite maximal inhaled therapy
• Poor response to conventional treatments

Clinical Decision Algorithm

1. Confirm eosinophilic phenotype:

   • Blood eosinophil count ≥150 cells/μL at screening or ≥300 cells/μL in the previous year
   • Consider higher thresholds (≥300 cells/μL) for better response prediction

2. Verify treatment optimization:

   • Patient should be on maximal inhaled therapy (triple therapy with LAMA/LABA/ICS)
   • Assess adherence to current medications
   • Rule out other causes of symptoms or exacerbations

3. Select appropriate biologic:

   • Mepolizumab 100 mg subcutaneously every 4 weeks is the most studied option
   • Consider benralizumab for patients with very high eosinophil counts (≥220 cells/μL) and frequent hospitalizations

4. Monitor response:

   • Assess exacerbation frequency
   • Evaluate symptom control and quality of life
   • Continue therapy if clinically meaningful reduction in exacerbations occurs

Limitations and Considerations

• Biologics do not significantly improve quality of life measures in COPD 1
• Cost-effectiveness remains a concern given the high price of these therapies
• Limited long-term safety data specifically in COPD populations
• Recent evidence suggests no benefit in reducing time to readmission or death 3

Common Pitfalls

1. Misidentifying the phenotype: Ensure proper documentation of eosinophil counts before initiating therapy
2. Unrealistic expectations: Biologics reduce exacerbations but have limited impact on mortality or hospitalization rates
3. Inadequate baseline therapy: Optimize inhaled medications before considering biologics
4. Ignoring comorbidities: Address other conditions that may contribute to symptoms or exacerbations

Emerging Evidence

The American Thoracic Society/European Respiratory Society statement notes that biomarkers such as blood eosinophilia may predict responsiveness to anti-inflammatory therapies, including monoclonal antibodies that have shown efficacy in eosinophilic severe asthma 5. However, single mediator antagonists including IL-5 blocking antibodies have previously shown limited effectiveness in broader COPD populations 5.

The most recent evidence from a 2025 phase 2b trial showed that mepolizumab did not improve time to readmission or death in patients hospitalized with AECOPD and eosinophilia, though there was a trend toward reduction in moderate or severe exacerbations 3.