Why add inhaled corticosteroids (ICS) to triple therapy in Chronic Obstructive Pulmonary Disease (COPD) patients without steroid responsiveness or eosinophilia?

Adding Inhaled Corticosteroids to Triple Therapy in COPD Without Steroid Responsiveness or Eosinophilia

Triple therapy including inhaled corticosteroids (ICS) should be considered for COPD patients with severe disease (GOLD D) and history of frequent exacerbations, regardless of eosinophil count, as it reduces exacerbation risk and improves lung function beyond dual bronchodilator therapy alone. 1

Rationale for ICS in Triple Therapy

Exacerbation Prevention

• Triple therapy (LAMA/LABA/ICS) is recommended for patients with more severe COPD (GOLD category D) based on consensus guidelines 1
• Even in patients without high eosinophil counts, triple therapy can provide:
  • Improved lung function
  • Reduced use of rescue medication
  • Better health-related quality of life
  • Decreased dyspnea

Clinical Benefits Beyond Eosinophil Count

• While blood eosinophil count ≥2% (or ≥300 cells/μL) is a predictor of better ICS response 2, patients without eosinophilia may still benefit from:
  • Additional anti-inflammatory effects not captured by eosinophil count
  • Synergistic effects when ICS is combined with dual bronchodilators

When to Consider Triple Therapy with ICS

Patient Characteristics

• History of multiple or severe exacerbations despite appropriate maintenance bronchodilator use 3
• Severe airflow limitation (FEV1 <50% predicted) 1
• Persistent symptoms despite dual bronchodilator therapy 3

Risk-Benefit Assessment

• Benefits:

  • 17% reduction in moderate/severe exacerbations in overall COPD population 2
  • Improved symptom control
  • Better quality of life

• Risks:

  • Increased pneumonia risk (4% higher than with LABA alone) 1
  • Higher pneumonia risk in patients with:
    • Older age
    • Lower BMI
    • Greater overall fragility
    • Blood eosinophils <100 cells/μL 4

Clinical Approach to Triple Therapy

Step-wise Algorithm

1. Optimize dual bronchodilator therapy (LAMA/LABA) first
2. Consider adding ICS if:
   • Patient has ≥2 moderate exacerbations or ≥1 hospitalization per year despite dual therapy
   • Severe airflow limitation (FEV1 <50% predicted)
   • Significant symptom burden persists despite dual therapy

Monitoring After Initiating Triple Therapy

• Assess exacerbation frequency
• Monitor for pneumonia risk
• Evaluate symptom improvement and lung function
• Consider ICS withdrawal if no clear benefit after 3-6 months

Important Caveats

• ICS should never be used as monotherapy in COPD 3
• Long-term oral corticosteroids have numerous side effects with no evidence of benefits 1
• Consider single-inhaler triple therapy when available to improve adherence 3
• Regular follow-up is essential to assess benefit-risk balance

Triple therapy represents an important treatment option for patients with severe COPD and history of exacerbations, even without demonstrable eosinophilia or steroid responsiveness, though the magnitude of benefit may be greater in those with higher eosinophil counts.