What add-on therapy to Chronic Obstructive Pulmonary Disease (COPD) treatment is considered after Trelegy (fluticasone furoate/umeclidinium/vilanterol)?

From the Guidelines

For patients who require additional therapy beyond Trelegy (fluticasone furoate/umeclidinium/vilanterol) for chronic inflammatory obstructive disease (CIOD), the most appropriate add-on therapy is not recommended as per the 2023 Canadian Thoracic Society guideline 1. This guideline suggests that in individuals with stable COPD, at low risk of exacerbations, with a moderate to high symptom burden and/or health status impairment, and impaired lung function despite LAMA/LABA/ICS triple combination therapy, stepping down to LAMA/LABA dual therapy is not suggested, but it does not provide a clear recommendation for adding on therapy to Trelegy. However, considering the available evidence, adding a phosphodiesterase-4 (PDE-4) inhibitor such as roflumilast (Daliresp) could be an option, as it has been studied in patients with moderate to severe COPD, especially in those patients with a history of hospitalization for exacerbations 1. Some key points to consider when adding on therapy to Trelegy include:

• Ensuring optimal adherence to Trelegy and proper inhaler technique
• Guiding the choice of add-on therapy by the patient's specific phenotype, exacerbation history, and comorbidities
• Regularly reassessing efficacy and side effects of the add-on therapy
• Considering the potential benefits and risks of each add-on therapy option, including the increased risk of adverse events with certain medications. It's also important to note that the 2023 Canadian Thoracic Society guideline recommends against treatment with ICS monotherapy in all individuals with stable COPD and at a low risk of exacerbations, and suggests not stepping down to LAMA or LABA monotherapy in patients taking LAMA/LABA dual therapy 1.

From the FDA Drug Label

The two 6-month efficacy trials (Trials 7 and 8) which assessed the effect of roflumilast as add-on therapy to a long-acting beta agonist or long-acting anti-muscarinic. An additional placebo-controlled 1-year trial (Trial 9) evaluated the effect of roflumilast 500 mcg on COPD exacerbations when added to a fixed-dose combination (FDC) product containing an inhaled corticosteroid and long-acting beta agonist (ICS/LABA). The use of long-acting muscarinic antagonists was allowed

The FDA drug label supports the use of roflumilast as add-on therapy to a long-acting beta agonist or long-acting anti-muscarinic, such as Trelegy.

• Key points:
  • Roflumilast can be used as add-on therapy to a long-acting beta agonist or long-acting anti-muscarinic.
  • The use of long-acting muscarinic antagonists is allowed.
  • Roflumilast has been evaluated in clinical trials as add-on therapy to ICS/LABA 2

From the Research

Add-on Therapy to CIOD after Trelegy

• The studies provided do not directly address the use of add-on therapy to CIOD after Trelegy, but they do discuss the use of roflumilast as an add-on therapy for COPD.
• Roflumilast is a phosphodiesterase-4 inhibitor that has been shown to reduce the risk of COPD exacerbations and improve lung function in patients with severe COPD associated with chronic bronchitis and a history of exacerbations 3, 4, 5, 6.
• The addition of roflumilast to long-acting bronchodilators has been shown to reduce COPD exacerbations in patients with severe COPD 4.
• Roflumilast has also been shown to improve lung function, including increases in mean pre- and postbronchodilator forced expiratory volume in 1 second and forced vital capacity 3, 5.
• However, roflumilast is associated with adverse effects, including weight loss, diarrhea, nausea, and psychiatric disturbances 4, 5, 6.
• There is limited information on the use of roflumilast as an add-on therapy to CIOD after Trelegy, and further studies are needed to determine its efficacy and safety in this context.

Potential Benefits and Risks

• The potential benefits of adding roflumilast to CIOD after Trelegy include reduced COPD exacerbations and improved lung function 3, 4, 5, 6.
• However, the potential risks include adverse effects such as weight loss, diarrhea, nausea, and psychiatric disturbances 4, 5, 6.
• The decision to add roflumilast to CIOD after Trelegy should be made on a case-by-case basis, taking into account the individual patient's medical history, current symptoms, and potential risks and benefits 3, 4, 5, 6.

Clinical Evidence

• The clinical evidence for the use of roflumilast as an add-on therapy for COPD is based on several studies, including randomized controlled trials and observational studies 3, 4, 5, 6, 7.
• These studies have shown that roflumilast can reduce COPD exacerbations and improve lung function in patients with severe COPD associated with chronic bronchitis and a history of exacerbations 3, 4, 5, 6.
• However, further studies are needed to determine the efficacy and safety of roflumilast as an add-on therapy to CIOD after Trelegy.