What is the percentage risk of pneumonia associated with fluticasone (Trelegy) in patients with Chronic Obstructive Pulmonary Disease (COPD)?

Pneumonia Risk with Fluticasone in Trelegy for COPD Patients

Fluticasone-containing inhaled corticosteroids, including Trelegy, increase the risk of pneumonia in COPD patients by approximately 55-100%, with the absolute risk translating to a number needed to harm of 33 patients treated for 1 year to cause one pneumonia event. 1

Quantified Risk Data

Overall ICS-Associated Pneumonia Risk

• Inhaled corticosteroids increase pneumonia risk by 55% compared to placebo (relative risk 1.55,95% CI 1.33-1.80) in trials lasting up to 3 years 1
• Meta-analysis of 25 randomized controlled trials demonstrated a 59% increased risk of pneumonia with ICS use (RR 1.59,95% CI 1.33-1.90) 2
• Severe pneumonia risk more than doubles with ICS treatment (RR 2.17,95% CI 1.47-3.22) 2

Fluticasone-Specific Risk

• Fluticasone propionate carries a 101% increased risk of serious pneumonia (RR 2.01,95% CI 1.93-2.10), which is substantially higher than other ICS agents 3
• Korean population study found 79% increased pneumonia risk with fluticasone propionate (HR 1.79,95% CI 1.70-1.89) 4
• Fluticasone furoate (the specific ICS component in Trelegy) showed similar risk elevation at 80% (HR 1.80,95% CI 1.61-2.01) 4
• Direct comparison studies demonstrate fluticasone propionate users have 34% higher pneumonia risk compared to budesonide users (HR 1.34,95% CI 1.26-1.43) 5

Dose-Response Relationship

The pneumonia risk increases progressively with cumulative fluticasone dose: 3, 4

• Risk is evident even at the lowest cumulative doses (HR 1.35,95% CI 1.27-1.43) 4
• Risk escalates to HR 1.51 with moderate doses 4
• Highest doses carry approximately double the risk (HR 2.03,95% CI 1.89-2.18) 4
• Fluticasone propionate shows dose-dependent risk escalation from HR 1.06 at lowest quartile to HR 1.49 at highest quartile compared to budesonide 5

Time Course of Risk

The pneumonia risk persists throughout ICS treatment and resolves after discontinuation: 3, 6

• Risk is sustained with long-term use without plateau 3
• Upon discontinuation, risk reduction begins within the first month (20% reduction) 6
• Risk reduction reaches 50% by the fourth month after stopping 6
• Risk completely disappears after 6 months of discontinuation (RR 1.08,95% CI 0.99-1.17) 3

Clinical Context and Risk-Benefit Balance

The Canadian Thoracic Society establishes the clinical significance with specific metrics: 1

• Number needed to treat: 4 patients for 1 year to prevent one moderate-to-severe exacerbation with triple therapy versus dual bronchodilator therapy 1
• Number needed to harm: 33 patients for 1 year to cause one pneumonia event 1
• This 8:1 benefit-to-harm ratio supports ICS use in appropriate patients despite pneumonia risk 1

High-Risk Populations

Pneumonia risk is particularly elevated in patients with: 1

• Severe and very severe COPD (FEV1 <50% predicted) 1
• These same patients paradoxically derive the greatest benefit from ICS-containing regimens in terms of exacerbation reduction and mortality 1

Critical Clinical Caveats

Important considerations when prescribing fluticasone-containing triple therapy: 1, 7

• Pneumonia is a class effect of all ICS agents in COPD, though fluticasone carries higher risk than budesonide 1, 2
• No conclusive evidence of intra-class differences exists for fluticasone furoate versus fluticasone propionate specifically 1
• The 8% pneumonia rate with salmeterol/fluticasone compares to 4% with tiotropium alone in head-to-head trials 7
• Multiple other factors beyond ICS use contribute to pneumonia risk in COPD patients 1

Risk Mitigation Strategy

When prescribing Trelegy or other fluticasone-containing regimens: 1

• Reserve for patients with FEV1 <50% predicted AND ≥2 exacerbations per year despite optimal bronchodilator therapy 1
• Consider alternative ICS agents (budesonide) in patients at particularly high pneumonia risk 2, 5
• Use moderate rather than high ICS doses, as the ETHOS study showed no significant exacerbation difference but demonstrated mortality benefit with moderate dosing 1
• Monitor closely for early pneumonia symptoms given the sustained risk throughout treatment 3