What is the efficacy of Tezspire (tezepelumab) in managing Chronic Obstructive Pulmonary Disease (COPD)?

Efficacy of Tezepelumab (Tezspire) in COPD: COURSE Trial Results

Tezepelumab does not demonstrate significant efficacy in the general COPD population but may show promise in patients with higher blood eosinophil counts (≥150 cells/μL). 1

COURSE Trial Findings

The COURSE trial was a phase 2a randomized, placebo-controlled study evaluating tezepelumab in patients with moderate to very severe COPD. Key findings include:

• Primary endpoint not met: The annualized rate of moderate or severe COPD exacerbations over 52 weeks was 1.75 for tezepelumab versus 2.11 for placebo (rate ratio 0.83,90% CI 0.64-1.06, p=0.10) 1

• Subgroup analysis by blood eosinophil count (BEC):

  • BEC <150 cells/μL: No benefit (rate ratio 1.19,95% CI 0.75-1.90)
  • BEC 150-<300 cells/μL: Trend toward benefit (rate ratio 0.66,95% CI 0.42-1.04)
  • BEC ≥300 cells/μL: Stronger trend toward benefit (rate ratio 0.54,95% CI 0.25-1.15) 1

• Safety profile: Tezepelumab was well-tolerated with no new safety concerns identified 1

Mechanism of Action and Background

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin (TSLP), which has shown increased expression in COPD patients compared to healthy individuals 1. While it has been approved for severe asthma regardless of phenotype 2, its role in COPD remains investigational.

Current COPD Treatment Guidelines

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends:

1. Bronchodilators as cornerstone therapy:

   • LAMAs and LABAs significantly improve lung function, dyspnea, health status, and reduce exacerbation rates 3
   • LABA/LAMA combinations are more effective than monotherapy for preventing exacerbations 3

2. Anti-inflammatory treatments:

   • ICS combined with LABA is effective for patients with moderate to very severe COPD and exacerbations 3
   • Triple therapy (ICS/LAMA/LABA) improves lung function, symptoms, and health status compared to ICS/LABA or LAMA monotherapy 3

3. Other treatments:

   • PDE4 inhibitors for patients with chronic bronchitis, severe COPD, and history of exacerbations 3
   • Long-term azithromycin/erythromycin for exacerbation reduction 3

Clinical Implications for Tezepelumab in COPD

Based on the COURSE trial results:

1. General COPD population: Tezepelumab cannot be recommended for routine use in unselected COPD patients 1

2. Eosinophilic COPD: Patients with higher blood eosinophil counts (≥150 cells/μL) showed trends toward benefit, suggesting potential efficacy in this subgroup 1

3. Safety considerations: The safety profile was similar to placebo, with adverse events in 81% of tezepelumab patients vs. 75% of placebo patients, and serious adverse events in 30% of patients in both groups 1

Practical Recommendations

1. Standard COPD therapy should be optimized first:

   • LAMA/LABA combinations remain first-line for symptom control and exacerbation prevention 3
   • Add ICS for patients with blood eosinophil counts ≥300 cells/μL or history of asthma 4

2. Consider tezepelumab only in research settings or specialized centers:

   • Further studies are needed, particularly in patients with blood eosinophil counts ≥150 cells/μL 1
   • Not currently approved or recommended for COPD in treatment guidelines 3, 4

Pitfalls and Caveats

• Biomarker-guided therapy: Blood eosinophil count appears to be an important biomarker for potential response to tezepelumab in COPD, similar to its role in guiding ICS use 1

• Distinction from asthma: While tezepelumab has shown efficacy across asthma phenotypes 5, its efficacy in COPD appears more limited and potentially phenotype-dependent 1

• Ongoing research: The COURSE trial was a phase 2a study; larger phase 3 trials would be needed before any recommendations for clinical use could be made 1