What is the next best step for a patient with Chronic Obstructive Pulmonary Disease (COPD) who is not improving on Anoro Ellipta (umeclidinium and vilanterol), a combination of a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA)?

Next Step for COPD Patient Not Improving on Anoro Ellipta

Escalate to triple therapy (LAMA/LABA/ICS) if the patient has a history of exacerbations (≥2 moderate or ≥1 severe in the past year) and blood eosinophils ≥300 cells/μL, or add roflumilast if FEV1 <50% predicted with chronic bronchitis phenotype, or consider adding a macrolide in former smokers with recurrent exacerbations. 1

Determine the Reason for Lack of Improvement

The management pathway depends critically on whether the patient's primary problem is persistent symptoms versus ongoing exacerbations 1:

If Persistent Symptoms Without Exacerbations

• First, ensure pulmonary rehabilitation is initiated, as combining optimal pharmacotherapy with pulmonary rehabilitation is the most effective approach for alleviating dyspnea and improving health status 1
• Step up to triple therapy (LAMA/LABA/ICS) for patients with moderate to high symptom burden (CAT ≥10, mMRC ≥2) and impaired lung function (FEV1 <80% predicted) despite LAMA/LABA dual therapy 1
• The 2023 Canadian Thoracic Society guidelines provide strong evidence (moderate certainty) that triple therapy provides greater improvements in dyspnea and health status compared to LAMA/LABA dual therapy 1
• Do not add oral medications (phosphodiesterase-4 inhibitors, mucolytics, statins, theophylline) to LAMA/LABA therapy for symptom control, as these show no improvements in dyspnea, exercise tolerance, or health status 1

If Ongoing Exacerbations Despite LAMA/LABA

The approach differs based on blood eosinophil count and smoking status 1:

For Patients with Blood Eosinophils ≥300 cells/μL or Asthma-COPD Overlap:

• Escalate to triple therapy (LAMA/LABA/ICS) 1
• Triple therapy reduces mortality with moderate certainty of evidence in high-risk populations 2
• The 2023 Canadian Thoracic Society strongly recommends triple therapy for patients at high risk of exacerbations with moderate to high symptom burden 1

For Patients with Blood Eosinophils <100 cells/μL:

• Do not escalate to triple therapy 2
• Add roflumilast if FEV1 <50% predicted and chronic bronchitis phenotype, particularly if hospitalized for exacerbation in the previous year 1
• Add azithromycin in former smokers, though the possibility of developing resistant organisms must be factored into decision-making 1, 2

For Patients with Intermediate Eosinophils (100-300 cells/μL):

• Consider switching to LABA/ICS first; if this does not positively impact exacerbations/symptoms, add LAMA back to create triple therapy 1

Critical Safety Considerations

ICS-Related Pneumonia Risk:

• ICS increases pneumonia risk, particularly in patients with eosinophils <100 cells/μL 3, 2
• The GOLD guidelines note that ICS therapy is associated with elevated risk of adverse effects including pneumonia 3
• Do not continue ICS indiscriminately in patients without asthma features, elevated eosinophils, or exacerbation history 3, 2

When to Avoid ICS Escalation:

• Patients at low risk of exacerbations (≤1 moderate exacerbation in the past year without hospital admission/ED visit) 1
• Patients with recurrent pneumonia on ICS-containing regimens 2
• Patients with blood eosinophils <100 cells/μL without concomitant asthma 2

Additional Non-Pharmacologic Interventions

• Pulmonary rehabilitation is strongly recommended for all patients with high symptom burden (Groups B, C, D), considering individual characteristics and comorbidities 1
• Smoking cessation remains the single most important intervention if the patient is still smoking 2
• Influenza and pneumococcal vaccinations (PCV13 and PPSV23 for patients ≥65 years) 1
• Nutritional supplementation for malnourished patients 1

Common Pitfalls to Avoid

• Do not reflexively add ICS to LAMA/LABA without considering exacerbation history, eosinophil count, and asthma features 3, 2
• Do not delay triple therapy in high-risk exacerbators with appropriate indications, as this delays mortality benefit 2
• Do not add multiple oral medications for symptom control, as evidence shows no benefit 1
• Do not discontinue long-acting bronchodilators during acute illness, as this worsens outcomes 3
• Do not prescribe ICS-containing regimens to low-risk patients without exacerbation history 2