{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:24:23Z","timestamp":1792470263893,"version":"4.5.0"},"reference-count":39,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2025,1,14]]},"abstract":"<jats:sec id=\"ab-joi240127-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>The optimal inhaled reliever therapy for asthma remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To compare short-acting \u03b2 agonists (SABA) alone with SABA combined with inhaled corticosteroids (ICS) and with the fast-onset, long-acting \u03b2 agonist formoterol combined with ICS for asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-6\">\n                    <jats:title>Data Sources<\/jats:title>\n                    <jats:p>The MEDLINE, Embase, and CENTRAL databases were searched from January 1, 2020, to September 27, 2024, without language restrictions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-7\">\n                    <jats:title>Study Selection<\/jats:title>\n                    <jats:p>Pairs of reviewers independently selected randomized clinical trials evaluating (1) SABA alone, (2) ICS with formoterol, and (3) ICS with SABA (combined or separate inhalers).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-8\">\n                    <jats:title>Data Extraction and Synthesis<\/jats:title>\n                    <jats:p>Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses synthesized outcomes. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to evaluate the certainty of evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-9\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Asthma symptom control (5-item Asthma Control Questionnaire; range, 0-6, lower scores indicate better asthma control; minimum important difference [MID], 0.5 points), asthma-related quality of life (Asthma Quality of Life Questionnaire; range, 1-7, higher scores indicate better quality of life; MID, 0.5 points), risk of severe exacerbations, and risk of serious adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-10\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 27 randomized clinical trials (N\u2009=\u200950\u202f496 adult and pediatric patients; mean age, 41.0 years; 20\u202f288 male [40%]) were included. Compared with SABA alone, both ICS-containing relievers were associated with fewer severe exacerbations (ICS-formoterol risk ratio [RR], 0.65 [95% CI, 0.60-0.72]; risk difference [RD], \u221210.3% [95% CI, \u221211.8% to \u22128.3%]; ICS-SABA RR, 0.84 [95% CI, 0.73-0.95]; RD, \u22124.7% [95% CI, \u22128.0% to \u22121.5%]) with high certainty. Compared with SABA alone, both ICS-containing relievers were associated with improved asthma control (ICS-formoterol RR improvement [MID] in total score, 1.07 [95% CI, 1.04-1.10]; RD, 4.1% [95% CI, 2.3%-5.9%]; ICS-SABA RR, 1.09 [95% CI, 1.03-1.15]; RD, 5.4% [95% CI, 1.8%-8.5%]) with high certainty. In an indirect comparison with ICS-SABA, ICS-formoterol was associated with fewer severe exacerbations (RR, 0.78 [95% CI, 0.66-0.92]; RD, \u22125.5% [95% CI, \u22128.4% to \u22122.0%]) with moderate certainty. Compared with SABA alone, ICS-formoterol (RD, \u22120.6% [95% CI, \u22121.3% to 0%]) was not associated with increased risk of serious adverse events (high certainty) and ICS-SABA (RD, 0% [95% CI, \u22121.1% to 1.2%]) was not associated with increased risk of serious adverse events (moderate certainty).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-joi240127-11\">\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In this network meta-analysis of patients with asthma, ICS combined with formoterol and ICS combined with SABA were each associated with reduced asthma exacerbations and improved asthma control compared with SABA alone.<\/jats:p>\n                  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