Inhaled corticosteroids with short-acting β₂-agonists as rescue therapy for asthma: a systematic review and...

The Global Initiative for Asthma (GINA) recommends inhaled corticosteroid (ICS)-containing regimens for all patients, advising against short-acting β₂-agonist (SABA) monotherapy. While ICS-formoterol is the preferred reliever, the role of ICS-SABA remains less clearly defined.

We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP from inception to November 2025 without language restrictions.

Eligible studies were randomized controlled trials (RCTs) comparing as-needed ICS-SABA with SABA-only reliever therapy in patients with asthma. Random-effects models were used to pool relative risks (RR), hazard ratios (HR), mean differences (MD), and standardized mean differences (SMD).

Five RCTs were included in the meta-analysis. ICS-SABA significantly reduced exacerbation rates (RR = 0.69, 95% CI: 0.52-0.91), risk of at least one exacerbation (RR = 0.69, 95% CI: 0.51-0.93), and prolonged time to first exacerbation (HR = 0.74, 95% CI: 0.62-0.89). Only the rate interaction favored milder asthma (GINA steps 1-2; one trial); the time-to-first and risk interactions were nonsignificant. Symptom-control and quality-of-life estimates favored ICS-SABA but were nonsignificant; systemic corticosteroid exposure was markedly reduced (MD = -38.51 mg, 95% CI: -65.97 to -11.04). No increase in adverse or serious adverse events was observed.

ICS-SABA reliever therapy provides consistent reductions in asthma exacerbations and systemic corticosteroid use without compromising safety, supporting its role as a pragmatic alternative to ICS-formoterol rescue therapy. Future research should include head-to-head comparisons with ICS-formoterol, pediatric-focused trials, and long-term real-world studies to optimize asthma care.