Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study

Abstract

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 1 s [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 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV₁ at Day 85 (primary end point), 0-3 h 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: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV₁ after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2-0.0]; P≤0.05). More patients achieved clinically meaningful improvements in TDI score (≥1 unit) 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.

Keywords: COPD; LABA; LAMA; step-up; tiotropium; umeclidinium/vilanterol.

Figure 1

Summary of patient disposition. Notes: ^*Percentages may not add up due to rounding. Abbreviations: TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Figure 2

LS mean (SE) change from baseline in trough FEV₁ (ITT population). Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; SE, standard error; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Figure 3

Serial LS mean change (95% CI) from baseline in FEV₁ over 0–3 h on Day 1 (A) and Day 84 (B; ITT population). Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; ITT, intent-to-treat; LS, least squares; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Figure 4

Serial LS mean change (95% CI) from baseline in FEV₁ over 0–24 h on Day 1 (A) and Day 84 (B; 24-h population). Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 s; LS, least squares; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Figure 5

Responder analysis of clinically relevant change from baseline in breathlessness assessed by (A) TDI focal score, and health status assessed by either (B) SGRQ total score or (C) CAT score (ITT population). Notes: TDI responder defined as a ≥1-unit improvement from baseline; SGRQ total score responder defined as a ≥4-unit reduction from baseline; and CAT score defined as a ≥2-unit reduction from baseline. Abbreviations: CAT, COPD Assessment Test; CI, confidence interval; ITT, intent-to-treat; OR, odds ratio; SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.