What is the recommended approach for using Dupilumab (dupilumab) in a patient with chronic obstructive pulmonary disease (COPD) exacerbations?

Dupilumab for COPD Exacerbations

Dupilumab is FDA-approved and strongly recommended as add-on therapy to triple inhaled therapy (LAMA/LABA/ICS) for patients with COPD who have type 2 inflammation (blood eosinophils ≥300 cells/μL) and continue to experience exacerbations despite maximal inhaled therapy, reducing exacerbations by approximately 30% and improving lung function. 1, 2, 3

Patient Selection Criteria

Dupilumab should be considered specifically for COPD patients meeting ALL of the following criteria:

• Blood eosinophil count ≥300 cells/μL at screening 2, 3
• Already on triple therapy (LAMA + LABA + ICS) at maximal doses 2, 3
• History of ≥2 moderate or ≥1 severe exacerbations in the previous year while on triple therapy 2, 3
• Post-bronchodilator FEV1/FVC ratio <0.7 and FEV1 30-70% predicted 3
• Age 40-85 years with ≥10 pack-year smoking history 3
• Symptomatic COPD with chronic productive cough for ≥3 months in the previous year 3

Key exclusion: Do not use dupilumab in patients with a history of asthma, as these patients were specifically excluded from COPD trials and represent a different disease entity. 3

Evidence for Efficacy

The pooled analysis of the BOREAS and NOTUS phase 3 trials (n=1,874 patients) demonstrated robust benefits:

• Exacerbation reduction: 31% reduction in annualized moderate or severe exacerbations (rate ratio 0.687,95% CI 0.595-0.793; p<0.0001) 3
• Lung function improvement: Prebronchodilator FEV1 increased by 83 mL at week 12 compared to placebo (95% CI 42-125 mL; p<0.001), sustained through 52 weeks 2
• Quality of life: SGRQ score improved by -3.4 points more than placebo at week 52 (95% CI -5.5 to -1.3; p=0.002) 2
• Symptom reduction: E-RS-COPD score improved by -1.1 points more than placebo at week 52 (95% CI -1.8 to -0.4; p=0.001) 2

The efficacy was consistent regardless of baseline BODE index score or presence of emphysema, indicating broad applicability within the type 2 COPD population. 4, 5

Dosing and Administration

• Standard dose: 300 mg subcutaneously every 2 weeks 1, 2, 3
• Loading dose: Not required; steady-state concentrations achieved by week 16 1
• Route: Subcutaneous injection via pre-filled syringe or pen 1
• Duration: Continue indefinitely as long as clinical benefit persists and patient tolerates therapy 2, 3

Integration with Acute Exacerbation Management

During an acute COPD exacerbation, continue dupilumab unchanged while implementing standard exacerbation management. 6

Standard acute exacerbation treatment remains essential:

• Short-acting bronchodilators (salbutamol 2.5-5 mg + ipratropium 0.25-0.5 mg) every 4-6 hours via nebulizer 6, 7
• Oral prednisone 30-40 mg daily for exactly 5 days 6, 7, 8
• Antibiotics for 5-7 days if ≥2 cardinal symptoms present (increased dyspnea, increased sputum volume, increased sputum purulence) 6, 7
• Controlled oxygen targeting SpO2 88-92% with arterial blood gas within 1 hour 6, 7
• Noninvasive ventilation if pH <7.35 with hypercapnia 9, 6, 8

Do not escalate or modify dupilumab dosing during acute exacerbations; the benefit is in preventing future exacerbations, not treating acute events. 6

Safety Profile

The safety profile was favorable in the pooled analysis:

• Treatment-emergent adverse events, serious adverse events, and adverse events leading to discontinuation were similar between dupilumab and placebo groups 2, 3
• Most common adverse events: upper respiratory tract infections (33-41% vs 35% placebo) and injection-site reactions (13-26% vs 13% placebo) 10
• No increased risk of pneumonia compared to placebo, unlike ICS therapy 2, 3
• Dupilumab decreases total IgE by approximately 70% at 52 weeks, but antibody responses to non-live vaccines remain intact 1

Clinical Context and Positioning

Dupilumab represents a targeted biologic therapy for a specific COPD endotype—those with type 2 inflammation—and should not be used as a replacement for optimized triple inhaled therapy. 2, 3

The mechanism involves blocking IL-4 and IL-13 signaling by binding to the shared IL-4Rα receptor subunit, thereby inhibiting type 2 inflammatory responses including eosinophil activation, IgE production, and mucus hypersecretion. 1

Critical distinction: The blood eosinophil threshold of ≥300 cells/μL used for dupilumab eligibility is higher than the ≥100 cells/μL threshold sometimes used to guide ICS therapy decisions in COPD, reflecting the need for more pronounced type 2 inflammation to justify biologic therapy. 2, 3

Common Pitfalls to Avoid

• Do not use dupilumab in patients with blood eosinophils <300 cells/μL—the trials specifically enrolled only patients with ≥300 cells/μL, and efficacy in lower eosinophil populations is unproven. 2, 3
• Do not discontinue triple inhaled therapy when starting dupilumab—it is add-on therapy, not replacement therapy. 2, 3
• Do not confuse COPD with type 2 inflammation with asthma-COPD overlap—patients with asthma history were excluded from dupilumab COPD trials. 3
• Do not expect immediate benefit during acute exacerbations—dupilumab's effect is preventive, reducing future exacerbation rates over weeks to months. 2, 3
• Do not add dupilumab before optimizing triple inhaled therapy—ensure patients are on maximal doses of LAMA, LABA, and ICS with verified adherence and proper inhaler technique before considering biologic therapy. 6, 2