P234 QVA149 once daily improves lung function, dyspnoea and health status independent of prior medications and disease severity: the SHINE study

Introduction QVA149 is a novel, inhaled, once-daily, fixed-dose combination of the long-acting β2-agonist (LABA) indacaterol and the long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) in development for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The SHINE study compared the effects of QVA149 110/50 µg, indacaterol 150 µg, glycopyrronium 50 µg, tiotropium 18 µg and placebo in patients with COPD.1 Here, we present the data on improvements in lung function (forced expiratory volume in 1 second area under the curve [FEV1 AUC5 min-4 h] and trough FEV1), transition dyspnoea index (TDI) and St George’s Respiratory Questionnaire (SGRQ - total score) by prior medication use and COPD disease severity subgroups. Methods In this 26-week, multicentre, double-blind, parallel-group, placebo- and active-controlled (open-label tiotropium) study, patients aged ≥40 years with moderate-to-severe COPD (post-bronchodilator FEV1/forced vital capacity (FVC) <0.7 and FEV1 ≥30% to <80% predicted) and a smoking history of ≥10 pack-years were randomised to receive once-daily QVA149, indacaterol, glycopyrronium, tiotropium or placebo (2:2:2:2:1). Results Of the 2144 patients (mean age 63.9 years; mean FEV1 post-bronchodilator 55.2% predicted) who were randomised (QVA149 [n = 475], indacaterol [n = 477], glycopyrronium [n = 475], tiotropium [n = 483] and placebo [n = 234]), 89.1% completed the study. QVA149 showed significant improvements in lung function, dyspnoea and health status compared with placebo in patient subgroups based on prior medication use and COPD disease severity (Table 1). Additionally, FEV1 AUC5 min-4 hwas significantly improved for QVA149 versus placebo (p < 0.001) regardless of the prior medication use and disease severity. Conclusion With once-daily QVA149, significant improvements were seen in both moderate and severe COPD patients and independent of medications used before recruitment and randomisation into the SHINE study. Reference Bateman et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013 May 30. [Epub ahead of print]. Abstract P234 Table 1. Lung function, dyspnoea and health status improvements in QVA149 vs placebo — subgroup analyses based on prior medicationuse and disease severity. 1 LSM (SE) treatment difference of QVA149 vs placebo FEV1AUC5min-4h(L) Trough FEV1(L) TDI total score SGRQ total score Prior medication use β-agonist plus steroid 0.34 (0.030)*** 0.19 (0.030)*** 1.21 (0.406)** –4.09 (1.705)* LABA 0.36 (0.059)*** 0.25 (0.058)*** 0.71 (0.798)ns –0.34 (3.103)ns LAMA 0.33 (0.028)*** 0.22 (0.029)*** 1.48 (0.443)*** –5.94 (1.770)*** SABA 0.37 (0.032)*** 0.22 (0.031)*** 1.29 (0.430)** –3.10 (1.780)ns SAMA 0.30 (0.074)*** 0.18 (0.073)* 2.27 (1.135)* –3.24 (4.495)ns β-agonist plus anticholinergic 0.31 (0.075)*** 0.08 (0.079)ns 1.13 (1.222)ns –4.66 (4.935)ns None 0.30 (0.033)*** 0.17 (0.034)*** 0.97 (0.500)ns –2.30 (2.198)ns COPD severity Moderate 0.37 (0.021)*** 0.24 (0.021)*** 1.17 (0.294)*** –2.74 (1.257)* Severe 0.26 (0.031)*** 0.12 (0.031)*** 1.00 (0.433)* –3.77 (1.840)* ***P<0.001 **;P<0.01; *P<0.05; ns, non-significant LSM, least squares mean; SABA,short-acting β2-agonist; SAMA, short-acting muscarinic antagonist; SE, standard error