What is the role of biologics, such as mepolizumab (interleukin-5 inhibitor), in the treatment of a patient with chronic obstructive pulmonary disease (COPD) and eosinophilic inflammation?

Biologics in COPD: Role and Selection

Primary Recommendation

For patients with COPD and eosinophilic inflammation (blood eosinophils ≥300 cells/μL), dupilumab is the first-choice biologic therapy, as it reduces exacerbations by 32% and improves lung function above clinically meaningful thresholds in this population. 1, 2

Evidence-Based Biologic Selection Algorithm

Step 1: Confirm Eosinophilic COPD Phenotype

• Measure blood eosinophil count; threshold ≥300 cells/μL identifies patients most likely to benefit from biologic therapy 2
• Document history of exacerbations despite optimal inhaled therapy (LAMA/LABA or triple therapy) 1
• Evaluate for type-2 comorbidities: chronic rhinosinusitis with nasal polyps, eosinophilic asthma, atopic dermatitis, eosinophilic esophagitis 1

Step 2: Select Appropriate Biologic Based on Patient Profile

Dupilumab (anti-IL-4R):

• First-line choice for eosinophilic COPD 1
• Reduces exacerbations by 32% (RR 0.68,95% CI 0.59-0.79) with high certainty evidence 2
• In patients with eosinophils ≥300/μL, improves FEV1 by 0.13L (95% CI 0.06-0.19), exceeding the minimal clinically important difference of 0.1L 2
• Superior to mepolizumab, reducing exacerbations 26% more effectively (RR 0.74,95% CI 0.62-0.89) 2
• Provides excellent effect on quality of life with significantly reduced need for rescue oral corticosteroids 1

Mepolizumab (anti-IL-5):

• Consider specifically when patient has co-morbid highly eosinophilic asthma in addition to COPD 1
• In COPD with eosinophils ≥150/μL, reduces exacerbations by 19% (RR 0.81,95% CI 0.71-0.93) 3
• Reduces hospitalization rate by 10% (RR 0.90,95% CI 0.65-1.24) 3
• Does NOT improve FEV1 above clinically meaningful thresholds in COPD patients 2
• Recent evidence shows no benefit for time to readmission or death in patients hospitalized with acute exacerbations, even with eosinophils ≥300/μL 4

Benralizumab (anti-IL-5R):

• Alternative anti-IL-5 pathway agent for eosinophilic asthma 1
• In COPD with eosinophils ≥220/μL, reduces severe exacerbations requiring hospitalization by 37% (RR 0.63,95% CI 0.49-0.81) 3
• No meaningful effect on patient-relevant outcomes according to most recent network meta-analysis 2

Tezepelumab (anti-TSLP):

• May reduce exacerbations (RR 0.83,95% CI 0.61-1.12), but evidence is low certainty 2
• In eosinophil subgroup ≥300/μL, improves FEV1 by 0.15L (95% CI 0.05-0.26) 2
• No important effect on patient-relevant outcomes in overall COPD population 2

Administration Protocol

Initiation

• First 2 injections administered in hospital for training and monitoring for anaphylaxis (minimal risk) 1
• Subcutaneous injection sites: abdomen, thigh, or upper arm using auto-injector or pre-filled syringe 1
• Self-injection possible after initial supervised doses 1

Timeline Expectations

• Onset of effect occurs within weeks to months 1
• Continue existing long-acting bronchodilator maintenance therapy unchanged during biologic initiation 5

Safety Profile

All biologics (mepolizumab, benralizumab, dupilumab) demonstrate favorable safety:

• Little or no difference in serious adverse events compared to placebo 3
• Little or no difference in overall adverse events or side effects compared to placebo 3
• Treatment appears safe with no serious adverse events attributed to intervention 4, 3

Critical Pitfalls to Avoid

Patient Selection Errors

• Do not use mepolizumab as first-line in COPD without co-morbid highly eosinophilic asthma—dupilumab is superior 1, 2
• Do not initiate biologics in patients with eosinophils <300/μL—efficacy is substantially reduced or absent 2, 3
• Do not use mepolizumab immediately post-hospitalization for acute exacerbation—recent trial showed no benefit for readmission or mortality 4

Treatment Approach Errors

• Do not discontinue inhaled maintenance therapy when starting biologics—continue LAMA/LABA or triple therapy 5
• Do not expect immediate FEV1 improvements with mepolizumab—this drug does not achieve clinically meaningful spirometric changes 2
• Do not use biologics as monotherapy—they are adjunctive to optimal inhaled therapy 1

Quality of Life Considerations

• Biologics provide excellent effect on quality of life and relevant signs/symptoms in real-world experience 1
• Rescue oral corticosteroid need is significantly reduced 1
• Surgery or rescue interventions are seldom needed 1
• Significant percentage of patients achieve disease control 1

Future Considerations

Biologic therapy in COPD is rapidly evolving with lack of head-to-head comparative studies 1. Current recommendations are based on network meta-analyses and expert consensus from September-December 2024 1. The field will be revised as further evidence becomes available, particularly regarding optimal eosinophil thresholds and long-term outcomes 1, 2, 6.