Safety of inhaled glycopyrronium in patients with COPD: a comprehensive analysis of clinical studies and post-marketing data

Abstract

Anthony D D’Urzo,1 Edward M Kerwin,2 Kenneth R Chapman,3 Marc Decramer,4 Robert DiGiovanni,5 Peter D’Andrea,6 Huilin Hu,6 Pankaj Goyal,5 Pablo Altman6 1Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; 2Clinical Research Institute of Southern Oregon, PC, Medford, USA; 3Asthma and Airway Centre, University Health Network, Toronto Western Hospital, Toronto, ON, Canada; 4Respiratory Division, University of Leuven, Leuven, Belgium; 5Novartis Pharma AG, Basel, Switzerland; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Background: Chronic use of inhaled anticholinergics by patients with chronic obstructive pulmonary disease (COPD) has raised long-term safety concerns, particularly cardiovascular. Glycopyrronium is a once-daily anticholinergic with greater receptor selectivity than previously available agents. Methods: We assessed the safety of inhaled glycopyrronium using data pooled from two analysis sets, involving six clinical studies and over 4,000 patients with COPD who received one of the following treatments: glycopyrronium 50 µg, placebo (both delivered via the Breezhaler® device), or tiotropium 18 µg (delivered via the HandiHaler® device). Data were pooled from studies that varied in their duration and severity of COPD of the patients (ie, ≤12 weeks duration with patients having moderate or severe COPD; and >1 year duration with patients having severe and very severe COPD). Safety comparisons were made for glycopyrronium vs tiotropium or placebo. Poisson regression was used to assess the relative risk for either active drug or placebo (and between drugs where placebo was not available) for assessing the incidence of safety events. During post-marketing surveillance (PMS), safety was assessed by obtaining reports from various sources, and disproportionality scores were computed using EMPIRICA™. In particular, the cardiac safety of glycopyrronium during the post-marketing phase was evaluated.Results: The overall incidence of adverse events and deaths was similar across groups, while the incidence of serious adverse events was numerically higher in placebo. Furthermore, glycopyrronium did not result in an increased risk of cerebro-cardiovascular events vs placebo. There were no new safety reports during the PMS phase that suggested an increased risk compared to results from the clinical studies. Moreover, the cardiac safety of glycopyrronium during the PMS phase was also consistent with the clinical data.Conclusion: The overall safety profile of glycopyrronium was similar to its comparators indicating no increase in the overall risk for any of the investigated safety end points. Keywords: COPD, drug safety, glycopyrronium, post-marketing surveillance