What is the recommended use of Breztri (budesonide, glycopyrrolate, and formoterol) in chronic obstructive pulmonary disease (COPD) management?

Breztri in COPD Management

Breztri (budesonide/glycopyrrolate/formoterol) is recommended as a triple therapy for patients with moderate-to-very severe COPD who continue to experience exacerbations despite optimal treatment with dual bronchodilator therapy (LAMA/LABA) and have elevated blood eosinophil counts.

Positioning in COPD Treatment Algorithm

Breztri is a fixed-dose combination triple therapy containing:

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

The treatment algorithm for COPD follows a stepwise approach:

1. Initial therapy: For patients with mild symptoms (mMRC 0-1), short-acting bronchodilators as needed 1
2. Moderate symptoms: LAMA monotherapy is preferred over LABA for preventing exacerbations 1
3. Persistent symptoms: LAMA/LABA combination therapy 2
4. Triple therapy indication: For patients who develop additional exacerbations on LAMA/LABA therapy 2

Specific Indications for Breztri

Breztri is specifically indicated for:

• Patients with moderate-to-very severe COPD who continue to experience exacerbations despite optimal bronchodilator therapy 3
• Patients with blood eosinophil counts ≥300 cells/μL 1
• Patients with COPD Group D (high symptom burden and high exacerbation risk) 2

Clinical Evidence Supporting Breztri

The ETHOS trial demonstrated that Breztri:

• Significantly reduced the annual rate of moderate or severe COPD exacerbations compared to dual therapies (LAMA/LABA or ICS/LABA) 4
• Reduced the risk of all-cause mortality compared to glycopyrrolate/formoterol (LAMA/LABA) dual therapy 5
• Improved lung function and quality of life compared to dual therapies 3

The 320 μg budesonide formulation of Breztri showed a 24% reduction in exacerbation rate compared to glycopyrrolate/formoterol and 13% reduction compared to budesonide/formoterol 4.

Important Considerations and Precautions

• Pneumonia risk: Increased risk of pneumonia with ICS-containing regimens (3.5-4.5% with Breztri vs. 2.3% with LAMA/LABA) 4
• Not for acute relief: Formoterol component is not indicated for acute symptom relief; short-acting beta-agonists should be used for rescue 6
• Cardiovascular effects: Use with caution in patients with cardiovascular disorders due to potential effects of the LABA component 6
• Administration: Delivered via pressurized metered-dose Aerosphere inhaler using co-suspension delivery technology 3

Treatment Algorithm for COPD

1. Assess symptom burden and exacerbation history:

   • Low symptoms (mMRC 0-1): SABA as needed
   • Moderate symptoms (mMRC 2): LAMA monotherapy
   • Severe symptoms (mMRC ≥3) or history of exacerbations: LAMA/LABA

2. For patients on LAMA/LABA who continue to have exacerbations:

   • Check blood eosinophil count
   • If ≥300 cells/μL: Escalate to triple therapy with Breztri
   • Consider Breztri particularly for patients with chronic bronchitis phenotype

3. Monitor for:

   • Exacerbation frequency
   • Pneumonia risk
   • Proper inhaler technique
   • Treatment adherence

Common Pitfalls to Avoid

1. Initiating triple therapy too early: Triple therapy should not be first-line treatment but reserved for patients who continue to have exacerbations despite optimal dual bronchodilator therapy 2

2. Using for acute symptom relief: Breztri is not indicated for acute deteriorations of COPD or rescue therapy 6

3. Overlooking pneumonia risk: Patients on ICS-containing regimens should be monitored for pneumonia, especially those with risk factors 2, 4

4. Neglecting non-pharmacological interventions: Smoking cessation, pulmonary rehabilitation, and vaccinations remain cornerstone interventions alongside pharmacotherapy 1

In summary, Breztri provides a convenient single-inhaler triple therapy option for patients with moderate-to-very severe COPD who continue to experience exacerbations despite optimal dual bronchodilator therapy, particularly those with elevated blood eosinophil counts.