What is the indication and usage of Breztri (budesonide, glycopyrrolate, and formoterol) for chronic obstructive pulmonary disease (COPD)?

Breztri (Budesonide/Glycopyrrolate/Formoterol) for COPD

Breztri (budesonide/glycopyrrolate/formoterol) is indicated for maintenance treatment of patients with moderate to severe COPD who have a history of exacerbations despite treatment with dual therapy, with demonstrated benefits in reducing exacerbation rates and mortality compared to dual therapies. 1, 2, 3

Mechanism and Components

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

• Budesonide: An inhaled corticosteroid (ICS) that reduces airway inflammation
• Glycopyrrolate: A long-acting muscarinic antagonist (LAMA) that provides bronchodilation
• Formoterol: A long-acting β2-agonist (LABA) that provides bronchodilation

This combination is delivered via a pressurized metered-dose Aerosphere inhaler using co-suspension delivery technology 2.

Clinical Efficacy

Breztri has demonstrated superior efficacy compared to dual therapies in multiple outcomes:

• Exacerbation reduction: 24% lower rate of moderate/severe exacerbations compared to glycopyrrolate-formoterol (LAMA/LABA) and 13% lower compared to budesonide-formoterol (ICS/LABA) 3
• Mortality benefit: Significantly reduced all-cause mortality compared to LAMA/LABA therapy (hazard ratio 0.51; 95% CI, 0.33-0.80) 4
• Improved lung function: Greater improvements in FEV1 compared to dual therapies 3
• Symptom control: Beneficial effects on dyspnea, reduced rescue medication requirements, and improved health-related quality of life 2

Appropriate Patient Population

Breztri is most appropriate for:

1. Patients with moderate to severe COPD (post-bronchodilator FEV1/FVC <0.70 and FEV1 % predicted of 30-49%) 1
2. Patients with a history of exacerbations despite current therapy 5
3. Patients with persistent symptoms on dual therapy (either ICS/LABA or LAMA/LABA) 1
4. Patients with various chronic comorbidities, particularly cardiopulmonary-related conditions 5

Dosing

Breztri is available in two dosage strengths:

• Higher dose: 320 μg budesonide/18 μg glycopyrrolate/9.6 μg formoterol
• Lower dose: 160 μg budesonide/18 μg glycopyrrolate/9.6 μg formoterol

Both doses are administered twice daily via the Aerosphere inhaler 3.

Safety Profile

Breztri is generally well tolerated with a safety profile similar to its individual components:

• Common adverse effects: Dysphonia, oral candidiasis, headache, and upper respiratory tract infections 6
• Pneumonia risk: Incidence of confirmed pneumonia ranges from 3.5-4.5% in patients receiving Breztri compared to 2.3% in those receiving LAMA/LABA therapy 3
• Cardiovascular events: Deaths from cardiovascular causes occurred in 0.5% of patients receiving the higher-dose Breztri compared to 1.4% in the LAMA/LABA group 4

Clinical Considerations

• Patient selection: Most appropriate for patients experiencing symptoms and exacerbations despite current therapy 5
• Monitoring: Regular assessment of symptom control, exacerbation frequency, and potential adverse effects is necessary 1
• Inhaler technique: Proper inhaler technique should be ensured for optimal drug delivery 1
• Pneumonia risk: Patients should be monitored for signs of respiratory infection due to increased pneumonia risk, particularly in those who currently smoke, are ≥55 years old, have a history of pneumonia, have a BMI <25 kg/m², or have severe airflow limitation 1

Treatment Algorithm

1. First-line therapy: LAMA monotherapy for patients with moderate COPD and history of exacerbations 1
2. Second-line therapy: LAMA/LABA combination for patients with persistent symptoms despite LAMA monotherapy 1
3. Third-line therapy: Triple therapy with Breztri for patients with continued exacerbations or symptoms despite dual therapy 1, 6

Advantages Over Other Therapies

• Convenience: Single inhaler delivering three medications simplifies treatment regimen 2
• Improved adherence: Potential benefit to overcome adherence and technique-related barriers compared to multiple inhalers 6
• Superior efficacy: Better exacerbation prevention compared to dual therapies 3
• Mortality benefit: Reduced risk of death compared to LAMA/LABA therapy 4

Breztri represents an important advancement in COPD management, particularly for patients with more severe disease and frequent exacerbations who require intensification beyond dual therapy.