What is a suitable high-dose ICS (Inhaled Corticosteroid) plus LABA (Long-Acting Beta-Agonist) inhaler?

High-Dose ICS Plus LABA Inhaler Options for Asthma

For patients requiring step 5 care in asthma management, the preferred treatment is high-dose inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA), with options including fluticasone/salmeterol (Advair) and budesonide/formoterol (Symbicort). 1

Available High-Dose ICS/LABA Combinations

First-Line Options:

• Fluticasone/Salmeterol (Advair)

  • Available in high-dose formulation
  • Administered twice daily
  • Strong evidence for efficacy in reducing exacerbations and improving lung function 1

• Budesonide/Formoterol (Symbicort)

  • Available in high-dose formulation
  • Can be used both as maintenance and reliever therapy (SMART approach)
  • Shows significant improvement in fractional exhaled nitric oxide (FeNO), small airway parameters, and symptom control 2

• Fluticasone Furoate/Vilanterol (Breo Ellipta)

  • Once-daily dosing (improves adherence)
  • Provides 24-hour bronchodilation
  • Significantly reduces risk of asthma exacerbations by 20% compared to ICS alone 3
  • FDA-approved for maintenance treatment of asthma

Dosing Guidelines for High-Dose ICS

High-dose ICS is defined as:

• Beclomethasone HFA: >480 mcg daily
• Budesonide DPI: >1200 mcg daily
• Mometasone DPI: >400 mcg daily
• Fluticasone: varies by formulation 4

Clinical Decision Algorithm

1. Assess current control and adherence:

   • If patient is on medium-dose ICS/LABA with persistent symptoms
   • If patient has experienced severe exacerbations despite current therapy

2. Choose appropriate high-dose ICS/LABA based on:

   • Patient preference for dosing frequency:

     • Once-daily preference → Fluticasone Furoate/Vilanterol (Breo Ellipta)
     • Twice-daily acceptable → Fluticasone/Salmeterol (Advair) or Budesonide/Formoterol (Symbicort)

   • Need for rescue therapy with same device:

     • If needed → Budesonide/Formoterol (SMART approach)
     • Not needed → Any option suitable

3. Consider device type:

   • DPI (dry powder inhaler) preferred for most adults with adequate inspiratory flow
   • MDI (metered dose inhaler) with spacer if inspiratory flow is limited 1

Important Clinical Considerations

• Safety warning: LABAs should never be used as monotherapy for asthma control due to increased risk of asthma-related deaths. Always combine with ICS. 1, 4

• Monitoring: After initiating high-dose ICS/LABA therapy, assess symptom control after 2-4 weeks. Consider stepping down therapy if control is maintained for at least 3 months. 4

• Side effects: Monitor for oral thrush, dysphonia, and cough with high-dose ICS. Advise patients to rinse mouth after using ICS to reduce risk of oral candidiasis. 4

• Potential benefits of combination therapy: ICS and LABA have complementary mechanisms of action. ICS increase expression of beta2-receptors while LABAs may potentiate the molecular mechanism of corticosteroid actions, leading to enhanced anti-inflammatory effects. 5

• Adjunctive therapies: For patients with severe persistent asthma not controlled on high-dose ICS/LABA, consider adding omalizumab for those with allergies. 1

Evidence Comparison

The scientific evidence strongly supports combination ICS/LABA therapy over ICS monotherapy for patients requiring step 5 care. A systematic review found that combination therapy with fluticasone/salmeterol and budesonide/formoterol provided greater improvements in outcome measures than corresponding ICS and LABA monotherapies. 6

Recent evidence suggests that fluticasone furoate/vilanterol (Breo Ellipta) reduces the risk of severe asthma exacerbations by 20% compared to fluticasone furoate alone, with mean yearly rates of asthma exacerbations of 0.14 vs 0.19, respectively. 3

For patients with severe persistent asthma, high-dose ICS plus LABA is the preferred treatment according to the stepwise approach for managing asthma (Step 5), with consideration of adding omalizumab for patients with allergies. 1