What other long‑term maintenance therapies are available for an adult with chronic obstructive pulmonary disease besides the budesonide/formoterol inhaler?

Long-Term Maintenance Therapies for COPD Beyond Budesonide/Formoterol

For adults with COPD already on budesonide/formoterol, the most effective alternative or additional long-term maintenance therapies include long-acting muscarinic antagonists (LAMAs) such as tiotropium, dual bronchodilator combinations (LAMA/LABA), or escalation to triple therapy (LAMA/ICS/LABA) depending on exacerbation history and disease severity. 1, 2

Primary Alternative Maintenance Options

Long-Acting Muscarinic Antagonists (LAMAs)

• Tiotropium monotherapy is equally effective to ICS/LABA combinations for preventing COPD exacerbations and should be considered as a first-line alternative, particularly in patients concerned about pneumonia risk from inhaled corticosteroids. 1

• LAMAs reduce exacerbations by 13-25% compared to placebo, with similar effectiveness to long-acting β2-agonists and ICS/LABA combinations. 1

• Tiotropium is administered once daily (18 mcg), offering a simpler dosing regimen than twice-daily budesonide/formoterol. 3

Dual Bronchodilator Therapy (LAMA/LABA)

• LAMA/LABA combinations (such as tiotropium/olodaterol, umeclidinium/vilanterol, or glycopyrronium/indacaterol) are superior to ICS/LABA for lung function improvement and have lower pneumonia rates. 2

• These combinations improve lung function, health-related quality of life, and dyspnea without the increased pneumonia risk associated with inhaled corticosteroids. 1

• LAMA/LABA dual therapy was superior to ICS/LABA in preventing exacerbations in high-risk patients (GOLD Group D). 2

Triple Therapy Escalation

When to Add Triple Therapy

• Patients with ≥2 moderate exacerbations OR ≥1 hospitalization/ED visit in the past year should receive triple therapy (LAMA/ICS/LABA). 2

• Triple therapy is appropriate for patients with FEV₁ <50% predicted and chronic bronchitis phenotype. 2

• Blood eosinophil count ≥150 cells/mm³ predicts better response to the ICS component of triple therapy. 2

Triple Therapy Options

• Budesonide/glycopyrronium/formoterol (BREZTRI AEROSPHERE) is a fixed-dose triple combination that reduces moderate/severe exacerbations more than dual therapy and reduces all-cause mortality. 4, 5

• Adding tiotropium to existing budesonide/formoterol significantly increases predose FEV₁ by 6% (65 ml) and postdose by 11% (123-131 ml), reduces severe exacerbations by 62%, and improves health status. 6

• Triple therapy provides rapid and sustained improvements in lung function, morning symptoms, and reduces severe exacerbations compared to dual therapy. 6

Additional Oral Maintenance Therapies

Macrolide Antibiotics

• For patients with moderate to severe COPD who have ≥1 moderate or severe exacerbation in the previous year despite optimal inhaled therapy, long-term macrolide therapy (such as azithromycin) prevents acute exacerbations. 1

• Clinicians must monitor for QT interval prolongation, hearing loss, and bacterial resistance when prescribing macrolides. 1

Phosphodiesterase-4 Inhibitors

• Roflumilast should be added for patients with FEV₁ <50% predicted and chronic bronchitis who continue to exacerbate on triple therapy, particularly if hospitalized for exacerbation in the previous year. 2

Non-Pharmacologic Therapies

Pulmonary Rehabilitation

• Pulmonary rehabilitation improves health status and dyspnea in adults with bothersome respiratory symptoms and FEV₁ <60% predicted. 1

• This intervention provides clinically meaningful improvements in quality of life that complement pharmacologic therapy. 1

Supplemental Oxygen

• Long-term supplemental oxygen reduces mortality in symptomatic patients with resting hypoxia (relative risk 0.61,95% CI 0.46-0.82). 1

• Oxygen therapy should be prescribed for patients meeting criteria for resting hypoxemia. 1

Critical Pitfalls to Avoid

• Never use ICS monotherapy in COPD—inhaled corticosteroids should always be combined with at least one long-acting bronchodilator. 1, 2

• Do not add a separate ICS to existing triple therapy, as this creates duplicate ICS exposure without guideline support and increases pneumonia risk. 2

• Inhaled corticosteroids increase pneumonia risk whether classified as adverse events (OR 1.38,95% CI 1.10-1.73) or serious adverse events (OR 1.48,95% CI 1.13-1.93) compared to long-acting β-agonists alone. 1

• Avoid beta-blockers (including ophthalmic preparations) in all COPD patients as they antagonize bronchodilator effects. 2

Treatment Algorithm Based on Exacerbation History

For patients with 0-1 exacerbations per year without hospitalization:

• Consider switching from budesonide/formoterol to LAMA/LABA dual therapy to reduce pneumonia risk while maintaining exacerbation prevention. 2

For patients with ≥2 exacerbations or ≥1 hospitalization per year:

• Add tiotropium to existing budesonide/formoterol, or switch to fixed-dose triple therapy (budesonide/glycopyrronium/formoterol). 2, 6

For patients continuing to exacerbate on triple therapy:

• Add roflumilast if FEV₁ <50% with chronic bronchitis, or add long-term macrolide therapy. 1, 2