Medium-Dose Compared With High-Dose Inhaled Corticosteroids in Combination Triple Inhaler Therapy for Asthma: A Systematic Review and Meta-Analysis
In brief
High-dose triple inhaler cuts severe asthma attacks by 20%
In three trials of 3,800 patients, using a high-dose inhaled corticosteroid in an ICS/LABA/LAMA triple inhaler lowered the chance of at least one severe exacerbation by about one fifth (number needed to treat ≈ 33). It also improved lung function by roughly 50 mL and asthma control scores slightly, without changing emergency visits or hospitalizations, but clinicians must balance these modest gains against possible systemic steroid effects.
- Journal
- CHEST pulmonary (Q2)
- Published
- 21 February 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Samantha Warhurst, Ryan Cullen, Ross Sayers, Francesca Lynch, Joseph Kulathinal, Mark Weatherall, et al.
- PMID
- 42688694
- DOI
- 10.1016/j.chpulm.2026.100240
Why clinicians should know about it
- Picked for Otorhinolaryngology (top studies of the week, 6 September 2026): SR/MA of RCTs on high‑dose vs medium‑dose inhaled steroids
Abstract
BACKGROUND: Combination inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) triple therapy is used in severe asthma. The clinical effect of high-dose (HD) vs medium-dose (MD) ICSs in ICS/LABA/LAMA is unclear. RESEARCH QUESTION: What is the clinical effect of HD compared with MD ICSs in ICS/LABA/LAMA treatment of asthma? STUDY DESIGN AND METHODS: A systematic review and meta-analysis of randomized controlled trials including > 1 ICS dose in ICS/LABA/LAMA inhalers compared the outcomes of HD and MD ICS/LABA/LAMA. The primary outcome was the proportion of participants with ≥ 1 severe asthma exacerbations. Secondary outcomes included FEV1, the Asthma Control Questionnaire, emergency department visits, and hospital admissions. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations domains. RESULTS: Three randomized controlled trials (N = 3,804) were identified, comparing MD and HD ICS/LABA/LAMA containing fluticasone or mometasone. When comparing HD with MD ICS/LABA/LAMA for at least 1 severe exacerbation, the Peto OR was 0.81 (95% CI, 0.68-0.96; P = .01). This corresponds to a number needed to treat to prevent 1 severe exacerbation of 32.9. HD ICS/LABA/LAMA led to a higher FEV1 (mean difference, 50.8 mL; 95% CI, 29.5-72.2 mL; P < .001) and a lower (improvement) Asthma Control Questionnaire (mean difference, -0.09; 95% CI, -0.15 to -0.04; P < .001) than MD ICS/LABA/LAMA. There was no statistically significant difference in emergency department visits (Peto OR, 0.51; 95% CI, 0.25-1.04; P = .07) or hospitalizations (Peto OR, 0.65; 95% CI, 0.33-1.29; P = .22) between HD and MD ICS/LABA/LAMA. INTERPRETATION: Our results show that HD compared with MD ICS/LABA/LAMA reduces the odds of a severe exacerbation by about 20%. This absolute risk reduction was modest but may be clinically relevant for patients with high baseline exacerbation rates and those with high type 2 inflammation. At both the individual and population level, the use of HD ICS/LABA/LAMA needs to be considered alongside the potential systemic side effects. CLINICAL TRIAL REGISTRATION: PROSPERO Registry; No.: CRD42025634340; URL: https://www.crd.york.ac.uk/prospero/.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.