What is the most appropriate next step in management for a patient with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stage three COPD (Chronic Obstructive Pulmonary Disease) experiencing frequent exacerbations despite being on a LABA (Long-Acting Beta Agonist)?

From the Guidelines

For a patient with GOLD stage three COPD experiencing frequent exacerbations despite being on a LABA, the most appropriate next step is to escalate therapy to a combination of a LABA and a LAMA, as this approach has been shown to improve lung function and reduce exacerbation rates compared to LABA monotherapy. This recommendation is based on the most recent and highest quality evidence available, including the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD 1.

Key Considerations

• The addition of a LAMA to a LABA improves lung function by reducing cholinergic bronchomotor tone, which can help reduce exacerbation rates and improve symptoms.
• The use of a LABA/LAMA combination is preferred over a LABA/ICS combination due to the increased risk of pneumonia associated with ICS, as noted in the 2018 GOLD report 1.
• However, for patients with a history of exacerbations despite appropriate treatment with long-acting bronchodilators, long-term treatment with ICSs may be considered in association with LABAs, as stated in the 2017 GOLD report 1.

Additional Recommendations

• Pulmonary rehabilitation should be prescribed to improve exercise tolerance and reduce symptoms.
• Vaccination against influenza and pneumococcal disease should be ensured to reduce the risk of exacerbations.
• Smoking cessation must be strongly encouraged if the patient continues to smoke, as this remains the most effective intervention to slow disease progression.
• The use of a single inhaler once daily, such as umeclidinium/vilanterol, may be considered to improve adherence and reduce exacerbation rates.

Evidence-Based Decision Making

The decision to escalate therapy to a LABA/LAMA combination is based on the most recent and highest quality evidence available, including the 2023 Canadian Thoracic Society guideline on pharmacotherapy in patients with stable COPD 1. This guideline recommends the use of a LABA/LAMA combination for patients with COPD who experience frequent exacerbations despite being on a LABA. The use of a LABA/LAMA combination has been shown to improve lung function and reduce exacerbation rates compared to LABA monotherapy, and is preferred over a LABA/ICS combination due to the increased risk of pneumonia associated with ICS.

From the FDA Drug Label

The effect of tiotropium 5 mcg inhalation spray on exacerbations was evaluated in three 48-week randomized, double-blind, placebo-controlled clinical trials that included COPD exacerbations as the primary endpoint In a pooled analysis of the first two trials, tiotropium 5 mcg significantly reduced the number of COPD exacerbations compared to placebo with a rate ratio of 0.78 (95% CI 0.67,0.92). STIOLTO RESPIMAT Trial Evaluating Exacerbations The primary endpoint was the annualized rate of moderate to severe COPD exacerbations. STIOLTO RESPIMAT treatment did not demonstrate superiority to tiotropium 5 mcg inhalation spray for the primary endpoint, the annualized rate of moderate to severe COPD exacerbations, with a rate ratio of 0.93 (99% CI, 0.85-1.02, p=0.0498).

The most appropriate next step in management for a patient with GOLD stage three COPD experiencing frequent exacerbations despite being on a LABA is to consider adding an inhaled corticosteroid (ICS) or a phosphodiesterase-4 inhibitor to their treatment regimen, as the current medication (LABA) is not sufficient to control exacerbations. However, the provided drug label does not directly support this answer, and the information about the addition of an ICS is not present in the label. Key points:

• The patient is already on a LABA.
• The patient is experiencing frequent exacerbations.
• Tiotropium 5 mcg has been shown to reduce the number of COPD exacerbations compared to placebo.
• STIOLTO RESPIMAT did not demonstrate superiority to tiotropium 5 mcg inhalation spray for the primary endpoint of annualized rate of moderate to severe COPD exacerbations 2.

From the Research

Management of GOLD Stage Three COPD with Frequent Exacerbations

• For a patient with GOLD stage three COPD experiencing frequent exacerbations despite being on a LABA, the most appropriate next step in management involves considering the addition of a long-acting muscarinic antagonist (LAMA) to the treatment regimen 3, 4.
• The current GOLD recommendations suggest using LABA and LAMA in combination for patients with persistent symptoms or further exacerbations on LAMA therapy alone 4.
• The addition of inhaled corticosteroids (ICS) to LABA/LAMA is recommended only in patients with a history of frequent/severe exacerbations and high blood eosinophil counts, or in those with concomitant asthma 3, 5.
• Studies have shown that LABA/LAMA combinations are effective in preventing COPD exacerbations and improving symptoms, and are the preferred treatment option for preventing COPD exacerbations in the updated GOLD guidelines 6, 4.
• A personalized approach to treatment is advocated, taking into account the individual patient's characteristics, such as blood eosinophil counts, and history of exacerbations 5, 7.

Considerations for Treatment

• The choice of treatment should be based on the patient's specific needs and characteristics, including the presence of comorbidities and the risk of adverse effects 5, 7.
• The use of ICS should be limited to patients who are likely to benefit from it, and the risks and benefits of treatment should be carefully considered 3, 5.
• Regular monitoring and assessment of the patient's condition is necessary to adjust the treatment regimen as needed 6, 4.