Inhaled corticosteroids with short-acting β2-agonists as rescue therapy for asthma: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: 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. DATA SOURCES: We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP from inception to November 2025 without language restrictions. STUDY SELECTION: 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). RESULTS: 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. CONCLUSIONS: 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.