What is preferred over a short-acting beta-agonist (SABA) for relief during exacerbations in adult patients with mild to moderate asthma?

ICS/Formoterol is Preferred to SABA for Relief of Asthma Exacerbations in Mild to Moderate Asthma

For adult patients with mild to moderate asthma, inhaled corticosteroid (ICS)/formoterol is preferred to a short-acting beta-agonist (SABA) as relief for exacerbations. 1

Rationale for ICS/Formoterol as Preferred Reliever Therapy

• ICS/formoterol used as both maintenance and reliever therapy (SMART) is the preferred modality for patients ≥5 years old with mild to moderate asthma at steps 3 and 4 of treatment 1
• The combination provides both immediate symptom relief and anti-inflammatory effects, addressing the underlying pathophysiology of asthma exacerbations 2
• ICS/formoterol as-needed reduces the risk of severe exacerbations compared to SABA alone, with high-certainty evidence showing a 55% reduction in exacerbations requiring systemic steroids 3
• The combination reduces asthma-related hospital admissions or emergency department visits compared to SABA alone (65% reduction) 3

Comparison of Options in the Question

A. ICS/Formoterol (CORRECT ANSWER)

• Formoterol has a rapid onset of action similar to SABAs, making it effective for quick symptom relief 1
• The addition of ICS addresses the inflammatory component of asthma exacerbations 2
• Studies of SMART were primarily performed with budesonide/formoterol, showing superior outcomes compared to SABA alone 1
• The 2020 National Asthma Education and Prevention Program (NAEPP) guidelines specifically recommend ICS/formoterol as both maintenance and reliever therapy for steps 3 and 4 1

B. ICS Alone

• ICS alone lacks the rapid bronchodilator effect needed for immediate symptom relief during exacerbations 1
• While ICS addresses inflammation, it does not provide the quick relief of bronchospasm that is needed during an acute exacerbation 4
• Guidelines continue to recommend bronchodilators for immediate symptom relief 1

C. Formoterol Alone

• Long-acting beta-agonists (LABAs) including formoterol should not be used as monotherapy for asthma 1
• Formoterol monotherapy lacks the anti-inflammatory component needed to address the underlying pathophysiology of asthma 1
• FDA labeling for formoterol specifically warns against its use as monotherapy for asthma treatment 5

D. Indacaterol/Mometasone

• While this is another ICS/LABA combination, there is insufficient evidence supporting its use as reliever therapy in mild to moderate asthma 1
• Studies of SMART were almost exclusively performed with budesonide/formoterol, not indacaterol/mometasone 1
• Formoterol has a faster onset of action than other LABAs, making it more suitable for reliever therapy 1

Important Clinical Considerations

• Formoterol is the preferred LABA for reliever therapy due to its rapid onset of action; salmeterol has a slower onset and should not be used for this purpose 1
• Although the boxed warning regarding asthma-related death has been removed from ICS/LABA labels, SMART is technically an off-label use in the United States 1
• The evidence primarily supports budesonide/formoterol for this indication, though theoretically other ICS formulations combined with formoterol could be effective 1
• For patients with mild asthma (step 2), as-needed ICS/formoterol or concomitant ICS and SABA are both acceptable alternatives to daily low-dose ICS with SABA as needed 1

Potential Pitfalls and Caveats

• Ensure patients understand which inhaler to use as a reliever versus maintenance therapy when using the SMART approach 1
• Insurance coverage may be a barrier as some plans may not cover two canisters of the same ICS/LABA at once (one for maintenance, one for relief) 1
• Patient education is crucial to ensure proper use of ICS/formoterol as reliever therapy, as this represents a paradigm shift from traditional SABA-only relief 6
• Monitoring for adverse effects is important, though evidence suggests ICS/formoterol as needed may actually reduce the odds of adverse events compared to SABA alone 3