Author(s): Ferguson G.T.; Buhl R.; De la Hoz A.; Bothner U.; Voss F.; Anzueto A.; Calverley P.M.
Source: American Journal of Respiratory and Critical Care Medicine; 2018; vol. 197
Publication Date: 2018
Publication Type(s): Conference Abstract
Available at American Journal of Respiratory and Critical Care Medicine – from Edge Hill Aintree LIRC (lib302411) Local Print Collection [location] : Edge Hill Aintree LIRC.
Abstract:RATIONALE The safety profile of tiotropium in COPD has been well-characterized in numerous large clinical trials.1 Combining tiotropium with olodaterol in a single inhaler improved lung function and health status more than tiotropium alone in previous Phase III studies, without additional safety concerns.2 In this analysis, we have pooled the pivotal Phase III trials and a recently completed Phase IIIb trial to examine the safety of tiotropium/olodaterol compared with tiotropium in almost 10,000 patients to increase our ability to detect infrequent complications. METHODS TONADO 1 and 2 were two replicate, double-blind, Phase III, 52-week studies in which patients with moderate-to-very-severe COPD were randomized to receive once-daily tiotropium/olodaterol, tiotropium, or olodaterol (NCT01431274/NCT01431287).2 DYNAGITO was a double-blind, active-controlled, parallel-group, 52-week, Phase IIIb trial in which patients with COPD were randomized to receive once-daily tiotropium/olodaterol 5/5 mug or tiotropium 5 mug (NCT02296138). In both trials, patients continued with inhaled corticosteroids (ICS) if they were taking them at baseline. For this safety analysis, patients receiving tiotropium/olodaterol 5/5 mug or tiotropium 5 mug from both trials were included, and adverse event (AE) data were analyzed. RESULTS Overall, 9,942 patients were included in the analysis; 71.6% were male, mean age was 66 years, mean post-bronchodilator forced expiratory volume in 1 second (FEV1) was 1.222 L (45.6% predicted). At baseline, 65.4% of patients were receiving ICS (TONADO: 47.1%; DYNAGITO: 70.2%) and 59.7% were taking cardiovascular medication. The proportion of patients with an AE was similar with tiotropium/olodaterol (74.1%) and tiotropium (74.3%; exposure-adjusted rate ratio [RR] 0.96; 95% confidence interval [CI] 0.92-1.01), and marginally fewer patients reported serious AEs with tiotropium/olodaterol (19.7%) than with tiotropium (20.8%; RR 0.91; 95% CI 0.84-1.00) (Table). A significantly higher proportion of patients had AEs leading to discontinuation with tiotropium (7.9%) compared with tiotropium/olodaterol (5.9%; RR 0.72; 95% CI 0.62-0.84). There was no difference between treatment groups in the proportion of patients with major adverse cardiovascular events (MACE) or fatal MACE in the whole population. In patients with cardiac history, fewer patients had a MACE with tiotropium/olodaterol than tiotropium (RR 0.64; 95% CI 0.44-0.93) (Table). CONCLUSIONS The combination of tiotropium with olodaterol does not increase the risk of AEs compared with tiotropium alone, and may be associated with a lower risk of certain events.