Abstract Background Inhaled corticosteroids (ICS) can reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD), particularly in those with eosinophilic airway inflammation. However, treatment responses vary, and not all patients derive the same degree of benefit. Evidence from previous studies suggests that current smokers may respond less favourably to ICS, but findings have been inconsistent and based on limited data. Using the ICS-RECODE individual participant data (IPD) meta-analysis, we evaluated whether the effectiveness of ICS differs according to smoking status in COPD. Methods ICS-RECODE is a prospectively designed, two-stage IPD meta-analysis (PROSPERO ID: CRD42024508286). Individual participant data from randomised controlled trials (RCTs) were re-analysed using harmonised statistical models to assess interactions between smoking status (current versus former) and ICS treatment effects. Analyses were adjusted for established prognostic factors, including age, sex, prior exacerbation history, baseline symptoms and lung function, blood eosinophil count, concomitant COPD medications, and comorbidities. Interaction estimates from individual trials were pooled using random-effects meta-analysis to quantify the overall smoking status-treatment interaction. The credibility of observed effect modification was assessed using the ICEMAN instrument. Results Seventeen RCTs were included, contributing data from 46,109 participants. Significant interactions between smoking status and ICS treatment effect were observed for the rate of exacerbations requiring systemic corticosteroids, as well as for time to first severe exacerbation, time to first exacerbation of any severity, and time to first exacerbation treated with systemic corticosteroids. Across these outcomes, ICS were consistently less effective in current smokers than in former smokers. No significant interaction was observed for other exacerbation outcomes or for pneumonia risk. According to the ICEMAN assessment, the credibility of smoking status-ICS interactions was rated as moderate. Discussion Inhaled corticosteroids appear to prevent exacerbations more effectively in former smokers than in current smokers with COPD, particularly those exacerbations requiring systemic corticosteroids. These findings highlight the importance of considering smoking status when evaluating potential ICS benefit and support smoking cessation as an integral component of optimised COPD management. This abstract is funded by: National Institute of Health and Care Research (NIHR HTA, NIHR152516)
Mathioudakis et al. (Fri,) studied this question.
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