Effect of stepping up to high-dose inhaled corticosteroids in patients with asthma : UK database study

BACKGROUND: It is unclear whether patients with asthma benefit from stepping up to high-dose inhaled corticosteroids (ICS).; OBJECTIVE: To determine the effectiveness of stepping up to high-dose ICS.; METHODS: A historic cohort study of asthma patients (≥13 years old), identified from two large UK electronic medical record databases, was conducted. Patients who remained on medium-dose ICS were compared to those who stepped up from medium- to high-dose ICS, while patients who stepped up from low- to medium-dose were compared to those who stepped up from low- to high-dose ICS. Time to first severe exacerbation (primary outcome) between treatment groups was compared using multivariable Cox proportional hazards models, and number of exacerbations and antibiotics courses were analyzed using negative binomial regression. Inverse probability of treatment weighting was used to handle confounding.; RESULTS: The mean follow-up time to first exacerbation was 2.7 (SD 2.7) years for those who remained on stable medium-dose ICS and 2.0 (SD 2.2) years for those who stepped up from medium-to high-dose ICS. A similar pattern was noted for those who stepped-up from low- to medium-ICS dose (2.6 (SD 2.5) years) and from low- to high-dose ICS (2.3 (SD 2.5) years). Patients who stepped up from medium- to high-dose ICS (n=6,879) had a higher risk of exacerbations during follow-up compared to those who remained on medium-dose ICS (n=51,737; hazard ratio [HR] 1.17, 95% confidence interval 1.12-1.22). This was similar in patients stepping up from low- to high-dose (n=3,232) compared to low- to medium-dose (n=12,659) ICS (HR 1.10 [1.04-1.17]). A step-up to high-dose ICS was also associated with higher number of asthma exacerbations and antibiotics courses. No significant difference in associations was found across subgroups of patients with different blood eosinophil counts (BEC).; CONCLUSION: We found no evidence that a step-up to high-dose ICS is effective in preventing future asthma exacerbations. Copyright © 2022. Published by Elsevier Inc