What is the role of Breztri (budesonide, glycopyrrolate, and formoterol) in the management of Chronic Obstructive Pulmonary Disease (COPD)?

Role of Breztri in COPD Management

Breztri (budesonide/glycopyrrolate/formoterol) is recommended as a triple therapy for patients with moderate to severe COPD who have persistent symptoms and exacerbations despite dual therapy with LABA/LAMA or ICS/LABA combinations. 1, 2

Mechanism and Components

Breztri Aerosphere is a fixed-dose triple combination inhaler containing:

• Budesonide (inhaled corticosteroid/ICS)
• Glycopyrrolate (long-acting muscarinic antagonist/LAMA)
• Formoterol (long-acting β2-agonist/LABA)

This combination addresses multiple pathophysiological aspects of COPD:

• Bronchodilation (glycopyrrolate and formoterol)
• Anti-inflammatory effects (budesonide)

Clinical Evidence and Indications

Breztri is indicated for patients with:

• Moderate to severe COPD 2
• History of exacerbations despite optimal dual therapy 1, 3
• Blood eosinophil counts ≥300 cells/μL (strongest benefit) 1

The ETHOS trial demonstrated that Breztri 320/18/9.6 μg significantly:

• Reduced all-cause mortality compared to glycopyrrolate/formoterol (hazard ratio 0.51; 95% CI 0.33-0.80) 4
• Decreased exacerbation rates compared to dual therapies 2, 4
• Improved lung function and quality of life 2

Place in Treatment Algorithm

According to current guidelines, Breztri should be positioned in the following treatment sequence:

1. Initial therapy: SABA/SAMA as needed for Group A patients (low symptoms, low exacerbation risk) 1
2. Step up: LABA or LAMA for Group B patients (high symptoms, low exacerbation risk) 1
3. Further step up: LABA/LAMA combination for inadequate symptom control on monotherapy 1
4. Triple therapy with Breztri: For patients with persistent exacerbations on LABA/LAMA, especially with blood eosinophils ≥300 cells/μL 1, 2

Administration and Dosing

• Delivered via pressurized metered-dose Aerosphere inhaler 2
• Standard dosing: 320/18/9.6 μg twice daily (2 inhalations per dose) 3
• Can be used with a spacer device, which may improve drug delivery, particularly for patients with suboptimal inhalation technique 5

Safety Considerations

• Generally well-tolerated with a safety profile similar to the individual components 2
• Common adverse effects include:
  • Oral candidiasis (due to ICS component)
  • Hoarse voice
  • Potential increased risk of pneumonia (with ICS component) 6
  • Headache, cough, and dizziness 5

Patient Selection

Breztri is most appropriate for:

• Patients with COPD experiencing symptoms and exacerbations despite current therapy 7
• Patients with cardiopulmonary comorbidities 7
• Those with evidence of inflammatory component (elevated blood eosinophils) 1, 4

Practical Considerations

• Proper inhaler technique is essential for optimal drug delivery
• A spacer may significantly improve lung exposure, particularly for patients with suboptimal inhalation technique 5
• Regular monitoring for ICS-related adverse effects is recommended
• Avoid abrupt discontinuation

Limitations and Caveats

• Not indicated for treatment of acute exacerbations 8
• Higher cost compared to mono or dual therapy
• Limited long-term safety data beyond clinical trials
• Potential for overtreatment if prescribed to patients who could be adequately managed with less intensive therapy 1

Breztri represents an important advancement in COPD management, offering a convenient single-inhaler option for patients requiring triple therapy while demonstrating significant benefits for exacerbation reduction and mortality.