1 Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
2 Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
J Manag Care Spec Pharm. 2018 Jul;24(7):700-709. doi: 10.18553/jmcp.2018.24.7.700.
The FDA issued 2 main drug safety communications (DSCs) on the cardiovascular safety of tiotropium in March 2008 (warning of a potential increased stroke risk) and January 2010 (informing of an absence of a significant increased stroke risk or cardiovascular events based on findings from a large trial).
To describe the effect of the FDA DSCs on medication dispensing of tiotropium in a large U.S. claims database.
Initiation of tiotropium products among patients with chronic obstructive pulmonary disease (COPD) aged 40 years and older was determined monthly from 2006-2012 using medication dispensing from the IMS Lifelink Health Plan Claims Database. Similarly, monthly initiation of products containing long-acting beta-agonists (LABAs) was calculated to explore product switching. The effect of the 2008 and 2010 FDA DSCs was measured using interrupted time-series analysis. Subgroups of patients with greater cardiovascular risk were also examined.
A decreasing trend in initiation of tiotropium-containing products was present before the initial 2008 DSC. The decline in tiotropium initiation continued until January 2010, accompanied by an increased initiation of LABA-containing products in patients with COPD. In the presence of the existing decreasing trend, the initial DSC was followed by an immediate 2.8% (P = 0.02) further reduction in tiotropium initiation. Tiotropium initiation increased 2.5% (P = 0.03) immediately after the 2010 DSC, reducing the overall decline in rate and stabilizing (flattening) the trend. No significant changes in dispensing level or trend were observed among COPD patients with cardiovascular comorbidity.
Cardiovascular safety concerns may have affected tiotropium initiation as indicated by the decrease in tiotropium dispensing shown immediately following the initial DSC. The effect was alleviated as concerns lessened following the most recent DSC.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors are employed by the FDA and have no conflict of interest relevant to the content of this study. The views expressed herein do not necessarily represent the views of the FDA.
美国食品药品监督管理局（FDA）于 2008 年 3 月（警告潜在的卒中风险增加）和 2010 年 1 月（告知大型试验中未发现卒中风险或心血管事件显著增加）发布了 2 份关于噻托溴铵心血管安全性的主要药物安全性通信（DSC）。
描述 FDA DSC 对大型美国索赔数据库中噻托溴铵药物配给的影响。
使用 IMS Lifelink 健康计划索赔数据库中的药物配给，每月确定 40 岁及以上慢性阻塞性肺疾病（COPD）患者噻托溴铵产品的起始使用情况。同样，计算含有长效β-激动剂（LABA）的产品的每月起始使用情况，以探索产品转换。使用中断时间序列分析测量 2008 年和 2010 年 FDA DSC 的效果。还检查了具有更高心血管风险的患者亚组。
在最初的 2008 年 DSC 之前，噻托溴铵产品的起始使用呈下降趋势。在 2010 年 1 月之前，随着 COPD 患者中含有 LABA 的产品的起始使用增加，噻托溴铵的起始使用持续下降。在存在现有下降趋势的情况下，初始 DSC 之后立即出现 2.8%（P=0.02）的噻托溴铵起始进一步减少。2010 年 DSC 后，噻托溴铵的起始增加了 2.5%（P=0.03），从而降低了总体下降速度并稳定（变平）了趋势。在患有心血管合并症的 COPD 患者中，未观察到配给水平或趋势的显著变化。
心血管安全性问题可能影响了噻托溴铵的起始使用，这表明在初始 DSC 后，噻托溴铵的配给量立即减少。随着最近一次 DSC 后担忧减轻，效果得到缓解。
本研究未从公共、商业或非营利部门的任何特定资助机构获得任何资金。作者受雇于 FDA，与本研究内容无利益冲突。本文所表达的观点不一定代表 FDA 的观点。
