For a patient with mixed asthma and Chronic Obstructive Pulmonary Disease (COPD) with a history of exacerbations requiring hospitalizations and elevated blood eosinophils on Breyna (mepolizumab) for Maintenance and Reliever Therapy (MART), should I add a Long-Acting Muscarinic Antagonist (LAMA) to complete triple therapy or switch to a single inhaler triple therapy regimen?

Recommendation: Switch to Single-Inhaler Triple Therapy

For your patient with asthma-COPD overlap, frequent exacerbations requiring hospitalization, and elevated eosinophils, you should transition to a single-inhaler triple therapy (SITT) regimen rather than adding a separate LAMA to their current Breyna MART therapy. This approach provides mortality reduction, superior adherence, and maintains access to a separate short-acting bronchodilator for rescue use. 1, 2

Why Single-Inhaler Triple Therapy Over Adding LAMA

Single-inhaler triple therapy is strongly preferred over multiple-inhaler combinations because it improves adherence, reduces inhalation technique errors, and simplifies the treatment regimen—all critical factors for a patient with a history of hospitalizations. 1, 2, 3 The Canadian Thoracic Society explicitly states that SITT should be favored over multiple inhalers due to these proven benefits. 1

Mortality and Morbidity Benefits

Your patient meets the high-risk criteria that define who benefits most from triple therapy:

• History of severe exacerbations requiring hospitalization (≥1 severe exacerbation qualifies as high-risk) 1, 3
• Elevated blood eosinophils (patients with eosinophils ≥300 cells/μL particularly benefit from ICS-containing regimens) 2, 3, 4

Triple therapy reduces all-cause mortality compared to LAMA/LABA dual therapy in exactly this patient population, with moderate-to-high certainty evidence from the IMPACT and ETHOS trials. 1, 2, 3 The mortality benefit extends beyond preventing exacerbations to include cardiovascular outcomes. 2

Exacerbation Reduction

Triple therapy reduces the annual rate of moderate-to-severe exacerbations to 0.91 versus 1.21 for LAMA/LABA alone, and severe exacerbations requiring hospitalization to 0.13 per year versus 0.19 per year (hazard ratio 0.66; 95% CI 0.56-0.78). 2, 3 The number needed to treat is only 4 patients for 1 year to prevent one moderate-to-severe exacerbation. 2, 5

Addressing Your Rescue Inhaler Concern

Your concern about rescue therapy is valid and easily addressed: Single-inhaler triple therapy is used as maintenance therapy only, not as a rescue inhaler. 1 The Canadian Thoracic Society explicitly states that "SABD prn (as needed) should accompany all recommended therapies across the spectrum of COPD." 1

Your patient will maintain their separate short-acting bronchodilator (SABA or SAMA) for rescue use while taking the single-inhaler triple therapy as scheduled maintenance therapy. 1 This is standard practice and recommended across all COPD severity levels. 1

Specific Single-Inhaler Options

Available single-inhaler triple therapy combinations include:

• Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 2, 3
• Budesonide/glycopyrronium/formoterol fumarate 2, 3

Both have demonstrated reductions in annual moderate/severe exacerbations and mortality benefits with moderate-dose ICS (not requiring higher doses). 2, 3, 5

Safety Considerations and Monitoring

The overall clinical benefit of mortality reduction outweighs the pneumonia risk associated with triple therapy. 2, 5 The benefit-to-harm ratio is favorable at 8:1, with a number needed to harm of 33 patients for 1 year to cause one pneumonia versus a number needed to treat of 4 to prevent one exacerbation. 2, 5

Monitor closely for pneumonia, particularly given your patient's history of hospitalizations and severe airflow limitation. 2 Risk factors include current smoking, age ≥55 years, history of exacerbations or pneumonia, BMI <25 kg/m², and severe airflow limitation. 3

Long-Term Management Strategy

Continue the single-inhaler triple therapy long-term and do not step down to dual therapy in this high-risk patient with elevated eosinophils, as ICS withdrawal increases exacerbation risk. 2, 3 The Canadian Thoracic Society makes only a weak recommendation for stepping down in patients with moderate-to-high symptom burden, and your patient's hospitalization history argues strongly against this. 1

Ensure proper inhaler technique at every visit, as errors in inhaler handling lead to increased emergency department admissions, hospitalizations, and systemic corticosteroid requirements. 2

Critical Pitfall to Avoid

Do not continue the MART approach with Breyna (budesonide/formoterol) while adding triple therapy, as this would result in excessive ICS dosing and duplicate LABA therapy. 1, 3 The transition should be to single-inhaler triple therapy for maintenance plus a separate short-acting bronchodilator for rescue only. 1