Background
High doses of a maintenance inhaled corticosteroids (ICSs) in asthma may achieve only modest additional clinical benefit beyond low-to-medium doses and are associated with an increased risk of adverse systemic effects. The ICS dose-response relationship when administered as maintenance combination ICS/long-acting beta2-agonist (LABA) therapy is uncertain.
Research Question
What is the ICS dose-response of maintenance ICS/LABA therapy?
Study Design and Methods
A systematic review was conducted using MEDLINE, Embase, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov databases to identify randomized controlled trials that allocated participants to > 1 ICS dose category, per Global Initiative for Asthma categorization, administered in combination with ICS/LABA inhalers. Meta-analysis compared outcomes of high-dose (HD) and medium-dose (MD), HD and low-dose (LD), and MD and LD ICS/LABA. The primary outcome was the proportion of participants with ≥ 1 severe asthma exacerbation; secondary outcomes were patient-reported outcome measures of asthma control, spirometry, and serious adverse events. Certainty of evidence was assessed by using the Grading of Recommendations, Assessment, Development and Evaluations domains.
Results
Twelve randomized controlled trials (6,373 participants) were identified: 7 comparing HD vs MD ICS/LABA, 1 HD vs LD ICS/LABA, and 4 MD vs LD ICS/LABA. HD vs MD ICS/LABA reduced the odds of a severe asthma exacerbation (Peto’s OR, 0.81; 95% CI, 0.67-0.98) with high certainty. There were no other clinically important differences in efficacy or safety outcomes of HD vs MD ICS/LABA. There was no difference in all outcomes comparing HD with LD or MD with LD ICS/LABA.
Interpretation
Our results showed that maintenance HD ICS/LABA reduced the odds of a severe exacerbation by about 20% compared with MD ICS/LABA. The absolute reduction in severe exacerbation risk with HD ICS/LABA is determined by patients’ exacerbation risk, and this effect size may be clinically relevant for patients if this risk is high. Comparisons of other doses of ICS/LABA were limited by the number of identified studies, although no large difference in effect sizes were observed.
https://journal.chestnet.org/article/S0012-3692(25)05145-1/abstract
