What is a therapeutic interchange for a patient with Chronic Obstructive Pulmonary Disease (COPD) or asthma currently taking Trelegy (fluticasone furoate, umeclidinium, and vilanterol)?

Therapeutic Interchange for Trelegy

For patients currently on Trelegy (fluticasone furoate/umeclidinium/vilanterol triple therapy), the most appropriate therapeutic interchange is to separate the components into LABA/LAMA dual therapy (such as umeclidinium/vilanterol) plus a separate ICS/LABA combination (such as fluticasone furoate/vilanterol), though this approach uses multiple inhalers rather than single-inhaler triple therapy. 1, 2, 3

Understanding Trelegy Components

Trelegy Ellipta contains three active ingredients delivered in a single inhaler 4, 5:

• Fluticasone furoate (ICS) - 100 mcg
• Umeclidinium bromide (LAMA) - 62.5 mcg
• Vilanterol trifenatate (LABA) - 25 mcg

This combination is FDA-approved for once-daily maintenance treatment of moderate to severe COPD in patients not adequately controlled on ICS/LABA therapy. 2, 3

Direct Therapeutic Alternatives

Option 1: Separate Dual Therapy Inhalers (Preferred for Most Patients)

LABA/LAMA dual therapy should be the primary interchange for patients at low risk of exacerbations, as this approach avoids the increased pneumonia risk associated with ICS while maintaining bronchodilation. 1

• Umeclidinium/vilanterol (Anoro Ellipta) 62.5/25 mcg once daily
• This provides the two bronchodilators from Trelegy without the corticosteroid component 6
• LAMA/LABA combinations demonstrate superior improvements in lung function and lower pneumonia rates compared to ICS/LABA combinations 1

Option 2: ICS/LABA Plus Separate LAMA

For patients requiring continued ICS therapy (those with ≥2 exacerbations per year, blood eosinophils ≥150-200 cells/µL, or asthma-COPD overlap):

• Fluticasone furoate/vilanterol (Breo Ellipta) 100/25 mcg once daily PLUS
• Umeclidinium (Incruse Ellipta) 62.5 mcg once daily 2, 3
• This maintains all three drug classes but requires two separate inhalers 1

Option 3: Alternative Triple Therapy Combinations

If single-inhaler triple therapy is clinically necessary, no exact equivalent exists, but alternative triple combinations include:

• Budesonide/glycopyrrolate/formoterol (Breztri Aerosphere)
• Beclomethasone/glycopyrronium/formoterol (Trimbow)
• These use different specific agents within the same drug classes 1

Clinical Decision Algorithm

Step 1: Assess Exacerbation Risk

Low risk (≤1 moderate exacerbation in past year, no hospitalizations):

• Interchange to LABA/LAMA dual therapy (umeclidinium/vilanterol) 1
• Discontinue ICS component to reduce pneumonia risk 1

High risk (≥2 moderate exacerbations or ≥1 severe exacerbation requiring hospitalization):

• Continue triple therapy with either single-inhaler or multiple-inhaler approach 1

Step 2: Evaluate for Asthma-COPD Overlap

If concomitant asthma features present:

• Maintain ICS component; use ICS/LABA (fluticasone furoate/vilanterol) plus separate LAMA 1
• ICS/LABA combination is preferred over LAMA/LABA in this population 1

If pure COPD without asthma features:

• LAMA/LABA dual therapy is preferred 1

Step 3: Consider Blood Eosinophil Count

Eosinophils ≥150-200 cells/µL:

• Suggests greater ICS responsiveness; maintain triple therapy 1

Eosinophils <150 cells/µL:

• Consider stepping down to LABA/LAMA dual therapy 1

Critical Considerations When Switching

Monitoring After ICS Withdrawal

When stepping down from triple therapy to LABA/LAMA, monitor closely for:

• Worsening health status (CAT score increase) 1
• Decline in lung function (FEV1 decrease) 1
• Increased exacerbation frequency 1

The 2023 Canadian Thoracic Society guideline provides only a weak recommendation to continue triple therapy rather than stepping down in symptomatic patients, reflecting equipoise in the evidence. 1

Pneumonia Risk Considerations

ICS therapy increases pneumonia risk, particularly in severe COPD. 1

• This risk is dose-dependent and increases with disease severity 1
• Regular ICS treatment shows a 4% increased pneumonia risk compared to LABA alone 1
• For patients with recurrent pneumonia, strongly consider removing ICS component 1

Device and Adherence Factors

Single-inhaler triple therapy improves adherence compared to multiple inhalers. 5, 7

• If adherence is a concern, maintaining single-inhaler triple therapy may be preferable to multiple-inhaler regimens 5, 8
• The Ellipta device demonstrates good patient acceptance and proper technique 5

Common Pitfalls to Avoid

Do not use LABA monotherapy - this increases risk of serious asthma-related events in patients with any asthma component. 2, 3

Do not combine with additional LABA-containing products - risk of overdose and cardiovascular effects. 2, 3

Do not abruptly discontinue ICS in patients on chronic therapy - taper slowly to avoid adrenal insufficiency, particularly in those previously on systemic corticosteroids. 2, 3

Avoid beta-blocking agents (including ophthalmic preparations) in all COPD patients as they antagonize bronchodilator effects. 9

Do not use for acute symptom relief - Trelegy and all maintenance therapies are not indicated for acute bronchospasm; patients require separate rescue inhalers. 2, 3