What are examples of triple therapy inhalers for chronic obstructive pulmonary disease (COPD) and severe asthma?

Triple Therapy Inhalers for COPD and Severe Asthma

Triple therapy inhalers combine an inhaled corticosteroid (ICS), a long-acting β2-agonist (LABA), and a long-acting muscarinic antagonist (LAMA) in a single device, and are specifically indicated for symptomatic patients with COPD at high risk of exacerbations (≥2 moderate or ≥1 severe exacerbation per year). 1

Available Single-Inhaler Triple Therapy (SITT) Products

Currently Approved Triple Therapy Inhalers:

1. Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI)

• Brand name: Trelegy Ellipta 2, 3
• Dosing: Once-daily administration 4
• Components: Fluticasone furoate (ICS) + umeclidinium (LAMA) + vilanterol (LABA) 2, 3
• Available strengths: 100/62.5/25 mcg or 200/62.5/25 mcg 2
• Device: ELLIPTA dry powder inhaler 2
• Clinical evidence: Improves lung function, reduces exacerbations, and improves quality of life in COPD patients with frequent exacerbations 5, 4

2. Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium Bromide (BDP/FF/GB)

• Brand name: Trimbow 6
• Dosing: Twice-daily administration 6
• Components: Beclometasone dipropionate 100 mcg/formoterol fumarate 6 mcg/glycopyrronium bromide 12.5 mcg per puff 7
• Device: Extrafine hydrofluoroalkane pressurized metered dose inhaler 7
• Unique feature: Extrafine formulation allows better peripheral lung deposition 6, 7
• Clinical evidence: Superior to ICS/LABA combination and tiotropium monotherapy for lung function and exacerbation prevention 7

3. Budesonide/Glycopyrronium/Formoterol Fumarate

• Brand name: Breztri Aerosphere 8
• Components: Budesonide (ICS) + glycopyrronium (LAMA) + formoterol fumarate (LABA) 9
• Clinical evidence: The ETHOS trial demonstrated 24% reduction in exacerbations compared to LAMA/LABA alone, with mortality benefit at the 320 mcg budesonide dose 8, 10
• Recommended for: Patients with moderate to very severe COPD (FEV1 <80% predicted), moderate to high symptom burden, and history of exacerbations 8

Clinical Positioning and Patient Selection

Triple therapy should be initiated in patients meeting ALL of the following criteria: 1

• High exacerbation risk: ≥2 moderate exacerbations OR ≥1 severe exacerbation (requiring hospitalization/ED visit) in the past year 1
• Moderate to high symptom burden: CAT score ≥10 or mMRC ≥2 1
• Impaired lung function: FEV1 <80% predicted 1

Specific Populations Where Triple Therapy is Particularly Beneficial:

• Patients with blood eosinophil counts ≥300 cells/mL: ICS component provides additional anti-inflammatory benefit 8
• Severe to very severe COPD: Particularly those with frequent exacerbations despite dual therapy 9, 7
• Asthma-COPD overlap syndrome (ACOS): Triple therapy addresses both bronchodilation and inflammation 9

Important Clinical Considerations

Advantages of Single-Inhaler Triple Therapy:

• Improved adherence compared to multiple-inhaler regimens 1, 8
• Reduces mortality compared to dual LABA/LAMA therapy in high-risk patients 1, 8
• Greater reduction in exacerbations than dual therapy 8, 7
• Improved lung function, symptoms, and quality of life 5, 7

Safety Monitoring Requirements:

• Pneumonia risk: 4% increased risk with ICS-containing regimens (number needed to harm = 33 for one year of treatment) 8, 10
• Monitor regularly for pneumonia, especially in patients who are: 8, 10
  • Current smokers
  • Age ≥55 years
  • Prior exacerbations/pneumonia history
  • BMI <25 kg/m²
  • Severe airflow limitation

Critical Pitfalls to Avoid:

• Never use ICS as monotherapy in COPD—always combine with long-acting bronchodilators 1
• Do not step down from triple therapy to dual therapy in patients with high exacerbation risk, as this increases moderate-severe exacerbations, particularly in those with blood eosinophils ≥300 cells/mL 10
• Avoid adding a second LAMA to triple therapy—there is no evidence supporting dual LAMA therapy and it poses unnecessary risks 11
• Do not use oral corticosteroids for maintenance treatment 1, 10

Dosing Considerations:

• Higher ICS doses are not typically necessary—the dose-response curve is relatively flat, and higher doses increase adverse effects without proportional benefit 10
• The ETHOS study showed no significant difference in exacerbation reduction between moderate (320 mcg) and low (160 mcg) dose budesonide, though mortality benefit favored the moderate dose 10

Guideline Recommendations

The 2023 Canadian Thoracic Society guidelines strongly recommend LAMA/LABA/ICS triple combination therapy over LAMA/LABA dual therapy due to greater reduction in mortality, improved lung function, and better quality of life in patients with severe COPD 1, 8. Triple therapy should preferably be administered as single-inhaler triple therapy (SITT) rather than multiple inhalers, though some patients may prefer separate devices 1.