D'Urzo Anthony D, Kerwin Edward M, Chapman Kenneth R, Decramer Marc, DiGiovanni Robert, D'Andrea Peter, Hu Huilin, Goyal Pankaj, Altman Pablo
Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
Clinical Research Institute of Southern Oregon, PC, Medford, USA.
Int J Chron Obstruct Pulmon Dis. 2015 Aug 11;10:1599-612. doi: 10.2147/COPD.S81266. eCollection 2015.
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.
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.
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.
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.
慢性阻塞性肺疾病（COPD）患者长期使用吸入性抗胆碱能药物引发了对长期安全性的担忧，尤其是心血管方面。格隆溴铵是一种每日一次的抗胆碱能药物，其受体选择性高于以往可用药物。
我们使用来自两个分析集的数据评估了吸入性格隆溴铵的安全性，这些数据涉及六项临床研究以及4000多名接受以下治疗之一的COPD患者：50μg格隆溴铵、安慰剂（均通过Breezhaler装置给药）或18μg噻托溴铵（通过HandiHaler装置给药）。数据来自患者COPD病程和严重程度各异的研究（即病程≤12周的中度或重度COPD患者；以及病程>1年的重度和极重度COPD患者）。对格隆溴铵与噻托溴铵或安慰剂进行了安全性比较。使用泊松回归评估活性药物或安慰剂（以及在无安慰剂的药物之间）的相对风险，以评估安全事件的发生率。在上市后监测（PMS）期间，通过从各种来源获取报告来评估安全性，并使用EMPIRICA计算不成比例分数。特别评估了格隆溴铵在上市后阶段的心脏安全性。
各组不良事件和死亡的总体发生率相似，而安慰剂组严重不良事件的发生率在数值上更高。此外，与安慰剂相比，格隆溴铵并未导致脑血管心血管事件风险增加。在PMS阶段没有新的安全报告表明与临床研究结果相比风险增加。此外，格隆溴铵在PMS阶段的心脏安全性也与临床数据一致。
格隆溴铵总的安全性概况与其对照药物相似，表明任何研究的安全终点的总体风险均未增加。
