Umeclidinium/Vilanterol As Step-Up Therapy From Tiotropium In Patients With Moderate Copd: A Randomized, Parallel-Group, 12-Week Study

Introduction: Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).Methods: In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for >= 3 months at screening (forced expiratory volume in 1s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score. 1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 mu g or TIO 18 mu g for 12 weeks. Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs).Results: Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88mL at Day 85 [95% confidence interval {CI}: 45-131]; P. 0.001) and FEV1 after 5min on Day 1 (50mL [95% CI: 27-72]; P. 0.001). Reductions in rescue medication use over 12weeks were greater with UMEC/VI versus TIO (LS mean change:-0.1puffs/d [95% CI:-0.2-0.0]; P. 0.05). More patients achieved clinically meaningful improvements in TDI score (. 1unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P. 0.01). Improvements in SGRQ and CAT scores were similar between treatments. The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).Conclusion: UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.