A Major Change in Asthma Management – Is This the Beginning of the End for SABAs?

A Major Change in Asthma Management – Is This the Beginning of the End for SABAs? Posted By:
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The most recent updated Global Initiative for Asthma (GINA) guidelines recommend that short-acting ß2-agonist (SABA) reliever therapy should not be used alone in the management of asthma, even mild, intermittent cases. This recommendation stems from the evidence showing that SABA therapy alone is associated with substantially more risk related to long-term SABA use (and therefore unchecked airway inflammation). The data also suggest that SABA overuse can result in down-regulation of ß2 receptors and therefore reduced response to SABA therapy. There is substantial evidence that SABA monotherapy also increases risk of exacerbations, especially in moderate to severe, persistent asthma.

In contrast, GINA guidelines recommend the use of an inhaled corticosteroids (ICS) plus long-acting ß2 agonist (LABA) as reliever therapy, specifically ICS/formoterol. Use of ICS/formoterol is associated with improved asthma control and lung function, and reduced asthma exacerbations. It was therefore determined that use of ICS/formoterol is more effective and safer than SABA therapy alone, which ultimately led to the GINA guideline updates. With the adoption of these new guidelines, single maintenance and reliever therapy, or SMART therapy, has become the standard of care in asthmatics requiring step-up therapy to GINA Step 2 or 3. This allows for a single inhaler to be both a patient’s preventative inhaler and their on-demand rescue inhaler, thus simplifying treatment plans.

Most studies looking at ISC/LABA therapy in this capacity focused on budesonide plus formoterol. Looking deeper into the data surrounding asthma exacerbations, studies show that, compared to SABA therapy alone, ICS/formoterol therapy reduces the incidence of severe exacerbations requiring management with oral corticosteroids, asthma-related hospital admissions, and ED visits by approximately 60%. In fact, when evaluating relative risk and assessing effects of ICS/formoterol or SMART therapy, the risk of severe exacerbation was lower across all stages of asthma severity. Overall, ICS/formoterol improves lung function parameters with an average increase in prebronchodilator FEV1 of 64 mL and reduction in fractional exhaled nitric oxide, a marker of airway inflammation, by 17% over SABA therapy alone. Overall, fewer adverse events were seen in the ICS/formoterol groups, vs only SABA therapy.

Unfortunately, despite the data leading to this landmark change in asthma management, there are still barriers to implementing this recommendation in clinical practice. One major barrier is the slower adoption of clinical guideline best practices by medical professionals and health insurance payors. Another major barrier is that despite having approval for use in asthma management, ICS/LABA is not FDA-approved for reliever or SMART therapy in the United States. Though there are sometimes ways around these hurdles, these patient access barriers remain significant. Another barrier or limitation could be that there is substantially less data surrounding the use of ICS/LABA as reliever use in children between the ages of 4 and 11 with asthma, though one study with SMART therapy in children showed excellent results.

Clinically, I have been able to implement these guidelines in practice and have seen first-hand the improved asthma control of asthma patients using ICS/formoterol vs SABA alone. Is this the beginning of the end for SABA inhalers? Probably not. But, as more evidence is published showing the overwhelming benefit of ICS/formoterol as reliever or SMART therapy, I am hopeful that these guidelines will eventually be able to be thoroughly implemented with fewer barriers, which will ultimately improve patient outcomes.

References

  1. Global Initiative for Asthma. 2023 GINA report, global strategy for asthma management and prevention. ginaasthma.org/2023-gina-main-report/. Accessed May 29, 2024.
  2. Reddel HK, FitzGerald JM, Bateman ED et al. GINA 2019: a fundamental change in asthma management. Eur Respir J. 2019;1901046.
  3. Beasley R, Bruce P, Houghton C, et al. The ICS/formoterol reliever therapy regimen in asthma: a review. J Allergy Clin Immunol Pract. 2023;11:762-772.e1.
  4. Crossingham I, Turner S, Ramakrishnan S et al. Combination fixed-dose beta agonist and steroid inhaler as required for adults or children with mild asthma. Cochrane Database Syst Rev. 2021;5:CD013518.
  5. Krings JG, Beasley R. The role of ICS-containing rescue therapy versus SABA alone in asthma management today. J Allergy Clin Immunol Pract. 2024;12:870-9.
  6. Levy ML, Beasley R, Bostock B, et al. A simple and effective evidence-based approach to asthma management: ICS-formoterol reliever therapy. Br J Gen Pract. 2024;74:86-89.

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Filed under: Preventive Medicine , Pulmonary Medicine , NPs & PAs , Allergy/Immunology

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