Background GOLD guidelines have changed from classifying COPD severity using pre-bronchodilator FEV1 to classifying severity based on post-bronchodilator FEV1. We therefore conducted a pooled post-hoc analysis of four budesonide/formoterol (Symbicort®) Turbuhaler® trials in COPD (which included patients based on pre-bronchodilator FEV1), assessing efficacy and safety of budesonide/formoterol in the post-bronchodilator FEV150– <70% of predicted normal (PN) subpopulation versus the all-patient population. This analysis supported the EU label change for Symbicort® Turbuhaler® to: ‘symptomatic treatment of patients with COPD with FEV1 < 70% PN (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy’.
Methods Four randomised, double-blind, active- and/or placebo-controlled, studies in patients with moderate to very severe COPD were analysed. Key study inclusion criteria were pre-bronchodilator FEV1 ≤50% PN; use of short-acting bronchodilator; ≥1 exacerbation in the past 12 months. Primary endpoints for the analysis were 3-month pre- and 3- and 12-months post-bronchodilator FEV1 and exacerbation rates at 3- and 12-months. Secondary endpoints included dyspnoea score, total symptom score, reliever medication use, night-time awakening and St George’s Respiratory Questionnaire. Results for the post-bronchodilator FEV150 – <70% PN subpopulation were compared with the all-patient population.
Results Of 3787 randomised patients, 832 (22.0%) had post-bronchodilator FEV150 – <70% PN. Baseline characteristics of the FEV150 – <70% subpopulation and the all-patient population were similar, except for baseline FEV1 parameters. The benefit of budesonide/formoterol versus placebo and formoterol on the primary and secondary endpoints were generally consistent between the FEV150 – <70% subpopulation and the all-patient population across all four studies and in the pooled analysis (Figure 1). No new safety signals were identified.
Conclusions In patients with COPD, the clinical efficacy and safety of budesonide/formoterol compared with placebo and formoterol was consistent between the post-bronchodilator FEV1 50 – <70% PN subpopulation and the all-patient population, confirming the positive benefit/risk ratio in COPD patients with a post-bronchodilator FEV1 <70% PN and a history of exacerbations.