What is the evidence for Breztri (budesonide, glycopyrrolate, formoterol) inhaler in the treatment of Chronic Obstructive Pulmonary Disease (COPD) compared to other triple therapies?

Evidence for Breztri (Budesonide/Glycopyrrolate/Formoterol) in COPD Treatment Compared to Other Triple Therapies

Breztri Aerosphere (budesonide/glycopyrrolate/formoterol) triple therapy significantly reduces exacerbation risk and mortality in patients with moderate-to-very severe COPD compared to dual therapies, making it a preferred option for patients with high symptom burden and exacerbation history. 1, 2

Efficacy of Triple Therapy in COPD Management

Exacerbation Reduction

• Triple therapy with ICS/LAMA/LABA (such as Breztri) is recommended for patients with more severe COPD (GOLD category D) and those with high risk of exacerbations 3
• The ETHOS trial demonstrated that Breztri (budesonide/glycopyrrolate/formoterol) at both 320/18/9.6 μg and 160/18/9.6 μg doses significantly reduced moderate or severe exacerbations compared to dual therapies:
  • 24% lower exacerbation rate vs. LAMA/LABA (glycopyrrolate/formoterol) with the 320 μg dose 1
  • 13% lower exacerbation rate vs. ICS/LABA (budesonide/formoterol) with the 320 μg dose 1
  • Similar reductions were seen with the 160 μg dose 1

Mortality Benefit

• The ETHOS trial showed a significant mortality reduction with Breztri 320/18/9.6 μg compared to glycopyrrolate/formoterol (hazard ratio 0.51; 95% CI, 0.33-0.80) 2
• This mortality benefit makes Breztri particularly valuable for patients with high exacerbation risk and moderate-to-very severe COPD 3
• The 2023 Canadian Thoracic Society guidelines specifically recommend LAMA/LABA/ICS triple therapy over LABA/LAMA dual therapy due to greater reduction in mortality 3

Lung Function and Symptom Improvement

• Triple therapy improves lung function, symptoms, and health status compared to dual therapies 3, 4
• The KRONOS study showed that Breztri significantly improved FEV1 AUC0-4 compared with budesonide/formoterol (116 mL improvement at week 24) 4
• Triple therapy provides better symptom control and improved quality of life compared to dual therapies 3, 4

Comparison with Other Triple Therapies

• While Breztri has shown clear benefits over dual therapies, there are limited direct head-to-head comparisons between Breztri and other triple therapy combinations 3
• The unique aspects of Breztri include:
  • Extrafine formulation allowing better lung deposition 5
  • Available in two ICS doses (320 μg and 160 μg of budesonide) allowing dose optimization 1
  • Delivered via a single metered-dose Aerosphere inhaler, potentially improving adherence 1

Safety Considerations

• The incidence of adverse events with Breztri is similar to dual therapies (61.7-64.5% across treatment groups in ETHOS) 1
• Pneumonia risk is slightly higher with ICS-containing regimens:
  • 3.5-4.5% incidence in ICS-containing groups vs. 2.3% in the glycopyrrolate/formoterol group 1
  • This is consistent with the known class effect of ICS therapies 3
• The benefit-risk ratio favors triple therapy in appropriate patients, with a number needed to treat of 4 to prevent one moderate-to-severe exacerbation vs. a number needed to harm of 33 for pneumonia 3

Patient Selection for Breztri

• Breztri is most appropriate for patients with:
  • Moderate to very severe COPD (FEV1 < 80% predicted) 3
  • Moderate to high symptom burden (mMRC ≥ 2 or CAT ≥ 10) 3
  • History of exacerbations (≥2 moderate or ≥1 severe exacerbation in the past year) 3, 1
  • Patients who continue to have symptoms or exacerbations despite dual therapy 3

Clinical Implementation

• For patients with high exacerbation risk and significant symptoms, initiate with triple therapy rather than stepping up from dual therapy 3
• For patients with blood eosinophil counts ≥300 cells/mL, triple therapy with ICS is particularly beneficial 3
• In patients who continue to exacerbate despite triple therapy, consider adding macrolide maintenance therapy or roflumilast/N-acetylcysteine 3
• The higher dose of budesonide (320 μg) in Breztri may provide additional mortality benefits compared to the lower dose (160 μg) 2

Practical Considerations

• Single-inhaler triple therapy may improve adherence compared to multiple inhalers 3
• Higher ICS doses are not typically necessary for optimal benefit in COPD, but the ETHOS study showed a mortality benefit with the moderate dose (320 μg) of budesonide 3, 2
• Regular monitoring for pneumonia is recommended, especially in patients with risk factors (current smokers, age ≥55 years, prior exacerbations/pneumonia, BMI <25 kg/m², severe airflow limitation) 3