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What Is the Optimal Reliever Therapy for Difficult-to-Control Asthma?

— Meta-analysis says anti-inflammatory relievers beat bronchodilators in reducing exacerbations

MedpageToday

BOSTON -- Inhaled corticosteroids (ICS) combined either with formoterol (Foradil) or short-acting beta-agonists (SABA) for asthma treatment were associated with reduced risks of severe exacerbations compared with bronchodilator-only relievers, a meta-analysis showed.

Compared with bronchodilator-only relievers, "high certainty" evidence showed that ICS-formoterol was associated with an absolute 10.3% lower risk of severe exacerbations (RR 0.65, 95% CI 0.60-0.72) while ICS-SABA was associated with an absolute 4.7% lower risk (RR 0.84, 95% CI 0.73-0.95).

The associations were similar for asthma-related hospitalizations and emergency department visits, reported Bradley Chipps, MD, of the Capital Allergy and Respiratory Disease Center in Sacramento, California, at the annual meeting of the American College of Allergy, Asthma & Immunology (ACAAI).

In addition, ICS-SABA and ICS-formoterol were associated with "modest" improvements in asthma control, without the risk of an increase in adverse events.

"Anti-inflammatory relievers are superior to bronchodilators as independent entities in reducing severe exacerbations and improving asthma control," Chipps said. "Optimal management of asthma may be driven by patient values and preferences, balancing key benefits and key harms in these patients, and clinical guidelines should be updated to reflect differences between reliever strategies."

Results from the study were published concurrently in .

The Global Initiative for Asthma (GINA) and the National Asthma Education and Prevention Program recommend ICS-formoterol as the preferred reliever over SABA alone, but the optimal asthma reliever strategy has been unclear since the FDA recently approved ICS-SABA as a reliever inhaler, according to the study authors. "Furthermore, guideline recommendations do not sufficiently differentiate between ICS-SABA and SABA-alone relievers, and the relative benefits of ICS-formoterol compared with ICS-SABA on clinical outcomes remain unclear," they added.

For the meta-analysis, Chipps and colleagues identified 27 randomized controlled trials (RCTs) involving 50,496 adult and pediatric patients. These trials evaluated SABA alone, ICS with formoterol, and ICS with SABA (combined or separate inhalers). Patients had a mean age of 41 years, and 41% were male.

Median treatment duration of the included RCTs was 26 weeks. All included trials of fast-onset, long-acting beta-agonists (alone or combined with an ICS) as a reliever therapy evaluated formoterol. Two trials (7%) evaluated patient populations comprised entirely of people ages 18 years or younger.

Regarding asthma symptom control, the analysis showed that both ICS-formoterol and ICS-SABA were associated with "modest" improvements in symptom control compared with bronchodilator-only relievers. Asthma Control Questionnaire scores showed a 4.1 percentage point improvement on the 7-point scale with ICS-formoterol and a 5.4 percentage point improvement with ICS-SABA compared with SABA alone.

"These effect sizes were small and potentially unimportant to patients," Chipps and colleagues observed.

Researchers also performed an indirect comparison of ICS-SABA and ICS-formoterol and found that ICS-formoterol was associated with an absolute 5.5% fewer severe exacerbations (RR 0.78, 95% CI 0.66-0.92). However, there was little to no difference between ICS-SABA and ICS-formoterol in asthma symptom control.

Regarding safety, the researchers found no differences in risk of harm between inhaler groups. Compared with SABA alone, neither ICS-formoterol (risk difference -0.6%) nor ICS-SABA (risk difference 0%) was associated with increased risk of serious adverse events.

The authors acknowledged several limitations to the study, particularly the fact that none of the identified RCTs directly compared ICS-formoterol with ICS-SABA. "Estimate imprecision reduced certainty about these results and findings reported here could change with a large RCT directly comparing these two inhalers," they wrote.

According to Chipps, the data from the meta-analysis will be used to inform an upcoming asthma guideline from the Joint Task Force on Practice Parameters, which is a collaborative partnership between ACAAI and the American Academy of Allergy, Asthma & Immunology.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by ACAAI and the American Academy of Allergy, Asthma & Immunology.

Chipps reported consulting fees from AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Novartis, and Sanofi-Regeneron. Co-authors reported various relationships with industry.

Primary Source

JAMA

Rayner DG, et al "Inhaled reliever therapies for asthma: a systematic review and meta-analysis" JAMA 2024; DOI: 10.1001/jama.2024.22700.