S29\u2005The impact of GOLD stage on the effectiveness of tiotropium/olodaterol in preventing COPD exacerbations in the DYNAGITO trial

Abstract

Rationale The DYNAGITO trial investigated the effect of bronchodilation on exacerbation rate in patients with COPD. The observed rates were 0.90 per patient-year with tiotropium/olodaterol (T/O) and 0.97 per patient-year with tiotropium alone (Tio) (rate ratio 0.93; 99% confidence interval 0.85–1.02; P=0.0498). We investigated whether the effect on exacerbation rate was the same across patients with varying degrees of baseline airflow limitation. Methods DYNAGITO was a 52-week, double-blind trial in which patients with COPD were randomized (1:1) to receive T/O 5/5µg or Tio 5µg once daily, delivered via Respimat® (NCT02296138). Patients continued to take inhaled corticosteroids (ICS) if receiving them at baseline. Inclusion criteria included post-bronchodilator FEV1 <60% predicted at baseline and at least one moderate or severe exacerbation in the previous 12 months. In this post hoc analysis, we grouped patients by baseline Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 2–4; there was a small number of patients classed as GOLD 1 (n=47), so we did not include this group. We used a negative binomial model adjusted for a number of covariates to calculate adjusted incidence rates and rate ratios. Results Overall, there were 2,784 patients classed as GOLD 2, 4,039 GOLD 3 and 992 GOLD 4. Baseline COPD treatment differed by GOLD stage. More patients were receiving a long-acting muscarinic antagonist (LAMA) only or LAMA/long-acting β2-agonist (LABA) in GOLD 2 (12.6% and 13.4%) than GOLD 3 (7.5% and 12.0%) or 4 (5.6% and 8.4%), while fewer patients were receiving LAMA/LABA/ICS in GOLD 2 (32.6%) than in GOLD 3 (42.8%) or 4 (47.7%). T/O reduced the exacerbation rate compared with Tio in GOLD 2 and 3 patients, but not in GOLD 4 patients (figure 1). Conclusion The results demonstrate that improving bronchodilation with T/O reduced the exacerbation rate compared with Tio in patients with GOLD 2 and 3 COPD. The lack of effect of bronchodilators in the most severely limited patients has been reported previously (Wedzicha et al. N Engl J Med 2016;374:2222–34) and may reflect the complex contributors to airflow obstruction in very severe COPD.Abstract S29 Figure 1 Exacerbation rate by GOLD stage 2–4 at baseline