James F Donohue1, Dave Singh2, Clara Munzu3, Sally Kilbride4, Alison Church5. 1. Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: james_donohue@med.unc.edu. 2. University of Manchester, Medicines Evaluation Unit, University Hospital of South Manchester Foundations Trust, Manchester, UK. Electronic address: DSingh@meu.org.UK. 3. Respiratory Medicines Development Centre, GSK, London, UK. Electronic address: clara.x.munzu@gsk.com. 4. Quantitative Sciences Division, GSK, London, UK. Electronic address: sally.5.kilbride@gsk.com. 5. Respiratory Medicines Development Center, GSK, Research Triangle Park, NC, USA. Electronic address: alison.x.church@gsk.com.
Abstract
PURPOSE: Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with umeclidinium/vilanterol provides additional benefit over umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV1] of ≥ 12% and ≥ 200 mL, Day 1) or non-responsive to monotherapy. METHODS: In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily umeclidinium 62.5 mcg, vilanterol 25 mcg, and umeclidinium/vilanterol 62.5/25 mcg (one treatment/14-day period; 10-14-day washout). Key endpoints were 0-6 h weighted mean FEV1 (Day 14) and trough FEV1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented. RESULTS:Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0-6 h weighted mean FEV1 versus umeclidinium in umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV1 occurred with umeclidinium/vilanterol versus umeclidinium in umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated. CONCLUSIONS: Once-daily umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to umeclidinium and vilanterol monotherapy than non-responders.
RCT Entities:
PURPOSE: Dual therapy with bronchodilators of different pharmacological classes may produce greater lung function improvements than either drug alone. However, the relationship between a patient's response to monotherapy and response to dual bronchodilator therapy is currently unknown. We aimed to investigate whether dual therapy with umeclidinium/vilanterol provides additional benefit over umeclidinium or vilanterol monotherapy in patients with chronic obstructive pulmonary disease (COPD) identified as responsive (increase from baseline in forced expiratory volume in 1s [FEV1] of ≥ 12% and ≥ 200 mL, Day 1) or non-responsive to monotherapy. METHODS: In two randomised, double-blind, three-way complete-block, cross-over studies (DB2116132 n = 207; DB2116133 n = 182; intent-to-treat), all patients (moderate-to-very severe COPD) were randomised to 1 of 6 sequences and received once-daily umeclidinium 62.5 mcg, vilanterol 25 mcg, and umeclidinium/vilanterol 62.5/25 mcg (one treatment/14-day period; 10-14-day washout). Key endpoints were 0-6 h weighted mean FEV1 (Day 14) and trough FEV1 (Day 15). Adverse events, vital signs and COPD exacerbations were assessed. Pooled data are presented. RESULTS:Umeclidinium/vilanterol significantly (p ≤ 0.001, unless stated otherwise) increased 0-6 h weighted mean FEV1 versus umeclidinium in umeclidinium-responders (+114 mL), versus vilanterol in vilanterol-responders (+92 mL) and versus umeclidinium (+70 mL) and vilanterol (+62 mL) in non-responders. Improvements in trough FEV1 occurred with umeclidinium/vilanterol versus umeclidinium in umeclidinium-responders (+77 mL), versus vilanterol in vilanterol-responders (+86 mL), and versus umeclidinium (+42 mL [p = 0.020]) and vilanterol (+58 mL) in non-responders. All treatments were well tolerated. CONCLUSIONS: Once-daily umeclidinium/vilanterol significantly improved lung function in patients with COPD, with quantitatively greater improvements in patients identified as responders to umeclidinium and vilanterol monotherapy than non-responders.
Authors: Peter Kardos; Sally Worsley; Dave Singh; Miguel Román-Rodríguez; David E Newby; Hana Müllerová Journal: Int J Chron Obstruct Pulmon Dis Date: 2016-11-25