Is Trelegy (fluticasone furoate, umeclidinium, vilanterol) helpful in managing asthma?

Trelegy for Asthma: Not FDA-Approved, But Emerging Evidence Shows Benefit

Trelegy (fluticasone furoate/umeclidinium/vilanterol) is currently FDA-approved only for COPD, not asthma, but recent high-quality clinical trial data demonstrates it can improve lung function in patients with inadequately controlled asthma on ICS/LABA therapy. 1, 2

Current FDA Status and Off-Label Use

• Trelegy is licensed as a once-daily maintenance treatment for adults with moderate to severe COPD who are not adequately treated by ICS/LABA combination 1
• It is not currently FDA-approved for asthma, making any use in asthma off-label 1
• The triple combination contains fluticasone furoate (ICS), umeclidinium (long-acting muscarinic antagonist/LAMA), and vilanterol (LABA) 1

Evidence Supporting Use in Asthma

The CAPTAIN Trial (2021) - Highest Quality Recent Evidence

The pivotal CAPTAIN study enrolled 2,439 patients with inadequately controlled asthma despite ICS/LABA therapy and demonstrated:

• Lung function improvement: FF/UMEC/VI 100/62.5/25 μg improved trough FEV1 by 110 mL versus FF/VI 100/25 μg (p<0.0001), and the 200/62.5/25 μg dose improved FEV1 by 92 mL versus FF/VI 200/25 μg (p<0.0001) 2
• Even the lower UMEC dose (31.25 μg) showed significant improvements: 96 mL for the 100/31.25/25 μg dose (p<0.0001) and 82 mL for the 200/31.25/25 μg dose (p=0.0002) 2
• Exacerbation reduction: Non-significant reductions in moderate/severe exacerbation rates were observed, with higher FF doses (200 μg) showing greater benefit than lower doses (100 μg) 2
• Symptom control: All treatment groups showed improvements in ACQ-7 scores exceeding the minimal clinically important difference of 0.5 points, with small additional benefits from adding UMEC (pooled FF/UMEC 62.5 μg/VI versus FF/VI: -0.09, p=0.0084) 2
• Safety profile: Adverse event rates were similar across groups (52-63%), with nasopharyngitis (13-15%), headache (5-9%), and upper respiratory tract infection (3-6%) being most common 2

Key Finding on Type 2 Inflammation Biomarkers

• Higher dose FF (200 μg versus 100 μg) primarily reduced exacerbation rates, particularly in patients with elevated blood eosinophil counts and exhaled nitric oxide 2
• By contrast, adding UMEC improved lung function regardless of type 2 inflammatory biomarker status 2

How This Fits Within Established Asthma Guidelines

Standard Stepwise Approach Still Applies

Current asthma guidelines establish a clear hierarchy that does not include triple therapy:

• Step 2 (mild persistent): Low-dose ICS is preferred first-line therapy 3, 4
• Step 3 (moderate persistent): Low-to-medium-dose ICS plus LABA is the preferred combination 3, 5
• Step 4: Medium-to-high-dose ICS/LABA, with consideration of adding leukotriene modifiers or theophylline 3, 5
• Step 5-6 (severe persistent): High-dose ICS plus LABA, with addition of biologics like omalizumab for patients ≥12 years with allergic asthma 3

Where Trelegy Would Theoretically Fit

Based on the CAPTAIN trial design and results, Trelegy would be positioned for:

• Patients with inadequately controlled moderate to severe asthma despite ICS/LABA therapy 2
• Patients requiring Step 4 or higher therapy who have not achieved control with standard combinations 2
• Particularly those without prominent type 2 inflammation (normal eosinophils/FeNO), where the LAMA component provides lung function benefit independent of inflammatory phenotype 2

Critical Caveats and Pitfalls

LAMA Use in Asthma is Not Standard

• Traditional asthma guidelines do not include LAMAs as standard add-on therapy 3
• The guidelines emphasize ICS as the cornerstone, with LABAs as the preferred add-on for inadequate control 3, 4
• LABAs must never be used as monotherapy for asthma due to increased risk of asthma-related death, and must always be combined with ICS 4, 5

Limited Exacerbation Benefit

• While Trelegy improved lung function significantly, the reduction in moderate/severe exacerbations was non-significant 2
• This contrasts with the robust exacerbation reduction seen with biologics like omalizumab in severe allergic asthma 3

Fixed Airflow Obstruction May Predict Response

• Earlier dose-ranging studies suggested patients with fixed airflow obstruction (incomplete reversibility) may derive greater benefit from FF/UMEC combinations (0.095-0.304 L improvement) compared to those with fully reversible obstruction (-0.084 to 0.041 L) 6
• This suggests Trelegy may be most appropriate for asthma patients with an "overlap" phenotype showing COPD-like features 6

Practical Clinical Algorithm

If considering Trelegy for asthma (off-label):

1. Confirm inadequate control on optimized ICS/LABA therapy (ACQ-6 score ≥1.5, SABA use >2 days/week, or exacerbations in past year) 2
2. Verify adherence and proper inhaler technique before escalating therapy 3
3. Check type 2 biomarkers (blood eosinophils, FeNO): If elevated, prioritize increasing ICS dose or adding biologics over adding LAMA 2
4. Assess for fixed obstruction: Perform pre- and post-bronchodilator spirometry; incomplete reversibility may predict better LAMA response 6
5. Consider alternative FDA-approved options first: High-dose ICS/LABA, add leukotriene modifier, or biologics (omalizumab) for appropriate candidates 3, 5
6. If using Trelegy: Start with FF/UMEC/VI 100/62.5/25 μg once daily, as this dose showed optimal lung function improvement in CAPTAIN 2
7. Monitor closely: Reassess at 12-24 weeks for lung function improvement, symptom control, and exacerbation frequency 2

Bottom Line

Trelegy improves lung function in patients with inadequately controlled asthma on ICS/LABA, but it is not FDA-approved for this indication and does not significantly reduce exacerbations 2. It represents a potential option for patients who have failed standard Step 4-5 therapy, particularly those with fixed airflow obstruction or low type 2 inflammation, but FDA-approved alternatives (higher-dose ICS/LABA, biologics) should generally be prioritized first 3, 2.