1 Dermato-venerology and Allergy Centre, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 ORCA, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 unknown4 Dermato-venerology and Allergy Centre, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
BACKGROUND: To further assess the safety profile of the fixed-dose combination of indacaterol and glycopyrronium (QVA149) and its monocomponents; we investigated the impact of individual patient-level factors and time by integrating the patient-level safety data from the QVA149 clinical programme with relevant information from the independent indacaterol and glycopyrronium safety databases. METHODS: Data from 11,404 patients with chronic obstructive pulmonary disease (COPD) were pooled from 14 clinical studies of QVA149, indacaterol and glycopyrronium of ≥3 month's duration with at least two of the treatment groups: QVA149 110/50 μg, glycopyrronium 50 μg, indacaterol 150 μg, placebo or tiotropium 18 μg. Overall hazard ratio (HR) was assessed between the active treatments and placebo and in various subgroups related to severity of airways obstruction, inhaled corticosteroid use, cardiovascular risk factors, sex, age and body mass index for death, serious cases of cardio- and cerebrovascular (CCV) events, major adverse cardiovascular events (MACEs), pneumonia, COPD exacerbations requiring hospitalisation or atrial flutter/fibrillation (AF/F). RESULTS: The HR for QVA149 versus placebo showed no significant increase in the overall risk for death (HR [95% confidence interval]: 0.93 [0.34-2.54]); CCV events (0.60 [0.29-1.24]); MACE (1.04 [0.45-2.42]); pneumonia (1.10 [0.54-2.25]); COPD exacerbations (0.60 [0.40-0.91]); and AF/F (1.03 [0.49-2.18]). Similar results were observed for indacaterol, glycopyrronium and tiotropium versus placebo for overall risk and in analysed subgroups. CONCLUSIONS: There was no increase in the risk for the investigated safety endpoints for the fixed-dose combination QVA149, and it had a comparable safety profile as its monocomponents and tiotropium versus placebo.