A pooled analysis of FEV₁ decline in COPD patients randomized to inhaled corticosteroids or placebo

Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV₁. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting ≥ 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV₁ decline in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV ₁ of 2.42 ± 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV₁ decline (-0.01 ± 0.09%; p = 0.86). The initial treatment effect was dependent on smoMng status and gender. Smokers who continued to smoke had a smaller increase in FEV₁ during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV₁ with ICS therapy than did male ex-smokers. Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV ₁ among those who completed these randomized clinical trials.