■内皮素受体拮抗剂是肺动脉高压(PAH)的一线疗法。班上批准的前两名特工,Bosentan和ambrisentan,作为风险评估和缓解策略(REMS)的一部分,最初对肝毒性进行了盒装警告,并要求每月进行肝功能检查(LFTs);然而,2011年,随着关于ambrisentan的进一步安全数据的出现,删除了盒装的肝毒性警告和LFT要求.
■分析在更改ambrisentan标签和REMS后,针对ambrisentan和Bosentan的使用和LFT监控的变化。
■这项连续的横断面研究使用了来自3个纵向医疗保健保险索赔数据库的数据-医疗补助,Optum的去识别的诊所形式学数据集市,和MerativeMarketscan-对服用ambrisentan和Bosentan的患者进行处方填充和LFT的中断时间序列分析。参与者是2007年7月1日至2018年12月31日期间服用ambrisentan和Bosentan处方的患者。数据分析于2021年4月至2023年8月进行。
■在2011年3月取消了对肝毒性的盒装警告和对ambrisentan的REMSLFT监测要求。
■主要结果是使用ambrisentan(即,在3个数据集中注册的每1000000个人中至少有1次配药的个人)与波生坦和LFT监测(即,在引发之前和第一次再填充之前,至少进行了1次有序测试的引发剂比例)。
■在研究期间,共有10261名患者接受了ambrisentan的处方(742名女性[72.5%];平均[SD]年龄,52.6[17.6]年),11159名患者接受了波生坦处方(7931名女性[71.1%];平均[SD]年龄,47.7[23.7]年)。取消ambrisentan盒装肝毒性警告和LFT监测要求与立即增加ambrisentan的使用相关(每百万参与者1.50名患者;95%CI,每百万参与者1.08至1.92名患者),但波生坦的使用没有显着变化。在药物开始之前(绝对减少13.1%;95%CI,-18.2%至-8.0%)和首次补充之前(绝对减少26.4%;95%CI,-34.4%至-18.5%)记录的LFT减少了安博生坦而不是波生坦。
■在这项关于安博森坦的连续横断面研究中,标签更改和取消与REMS相关的LFT要求与安博生坦的处方和测试行为的变化相关,而与波生坦无关.可能需要进一步的临床医生教育,以最大限度地发挥REMS计划的益处,并标记旨在确保高风险药物的安全管理的警告。
UNASSIGNED: Endothelin receptor antagonists are first-line therapy for pulmonary arterial hypertension (PAH). The first 2 agents approved in the class, bosentan and ambrisentan, initially carried boxed warnings for hepatotoxicity and required monthly liver function tests (LFTs) as part of a risk evaluation and mitigation strategy (REMS); however, in 2011, as further safety data emerged on ambrisentan, the boxed hepatotoxicity warning and LFT requirements were removed.
UNASSIGNED: To analyze changes in the use of and LFT monitoring for ambrisentan and bosentan after changes to the ambrisentan labeling and REMS.
UNASSIGNED: This serial cross-sectional study used data from 3 longitudinal health care insurance claims databases-Medicaid, Optum\'s deidentified Clinformatics Data Mart, and Merative Marketscan-to perform an interrupted time series analysis of prescription fills and LFTs for patients taking ambrisentan and bosentan. Participants were patients filling prescriptions for ambrisentan and bosentan from July 1, 2007, to December 31, 2018. Data analysis was performed from April 2021 to August 2023.
UNASSIGNED: Removal of the boxed warning for hepatotoxicity and the REMS LFT monitoring requirements on ambrisentan in March 2011.
UNASSIGNED: The primary outcomes were use of ambrisentan (ie, individuals with at least 1 dispensing per 1 000 000 individuals enrolled in the 3 datasets) vs bosentan and LFT monitoring (ie, proportion of initiators with at least 1 ordered test) before initiation and before the first refill.
UNASSIGNED: A total of 10 261 patients received a prescription for ambrisentan during the study period (7442 women [72.5%]; mean [SD] age, 52.6 [17.6] years), and 11 159 patients received a prescription for bosentan (7931 women [71.1%]; mean [SD] age, 47.7 [23.7] years). Removal of the ambrisentan boxed hepatotoxicity warning and LFT monitoring requirement was associated with an immediate increase in the use of ambrisentan (1.50 patients per million enrollees; 95% CI, 1.08 to 1.92 patients per million enrollees) but no significant change in the use of bosentan. There were reductions in recorded LFTs before drug initiation (13.1% absolute decrease; 95% CI, -18.2% to -8.0%) and before the first refill (26.4% absolute decrease; 95% CI, -34.4% to -18.5%) of ambrisentan but not bosentan.
UNASSIGNED: In this serial cross-sectional study of ambrisentan, labeling changes and removal of the REMS-related LFT requirement were associated with shifts in prescribing and testing behavior for ambrisentan but not bosentan. Further clinician education may be needed to maximize the benefits of REMS programs and labeling warnings designed to ensure the safe administration of high-risk medications.