Pharmacoepidemiology and Pharmacovigilance Division, Medicines for Human Use Department, Spanish Agency for Medicines and Medical Devices (AEMPS), Madrid, Spain.
Pharmacoepidemiol Drug Saf. 2024 Sep;33(9):e70004. doi: 10.1002/pds.70004.
Since late 2017, the use of ulipristal acetate 5 mg (UPA; Proprietary name: Esmya) has been under review in the European Union, due to an emerging hepatic risk. In February 2018 and in July 2018, the Spanish Agency of Medicines and Medical Devices and the marketing authorization holder put two risk minimization measures (RMM) in place, in order to inform about new safety information and to mitigate this risk. This study aims to assess RMM effectiveness in Spain, by performing an interrupted time-series (ITS) analyses, between 2014 and 2019.
Two quasi-experimental ITS analyses to examine the use of UPA before and after the RMM release were performed: (a) an ecological study using aggregated data from a drug consumption database; and (b) a study using primary healthcare data gathered from electronic clinical records.
Regulatory interventions were associated with an immediate and significant decrease level of DID (the number of DDD dispensed per 100 000 inhabitants and day) and incidence. The DID was 70% less than expected 12 months after the interventions. This value was 59% for the incidence. However, a change in the slope was not observed and the use started rising again in the last segment of the study period.
Despite RMM had an immediate strong impact on UPA use, the last segment upward trend in the long-term might have been affected by the lack of comparable therapeutic alternatives. Further studies should be performed to confirm the increase trend observed and analyze subsequent measures and additional data.
自 2017 年末以来，由于出现肝风险，欧洲联盟一直在审查屈螺酮 5 毫克（UPA；商品名：Esmya）的使用。2018 年 2 月和 2018 年 7 月，西班牙药品和医疗器械管理局和上市许可持有人实施了两项降低风险措施（RMM），以便告知新的安全性信息并降低这种风险。本研究旨在通过 2014 年至 2019 年的中断时间序列（ITS）分析评估西班牙的 RMM 效果。
为了检验 RMM 发布前后 UPA 的使用情况，进行了两次准实验 ITS 分析：（a）一项使用药物使用数据库汇总数据的生态研究；（b）一项使用电子临床记录中收集的初级保健数据的研究。
监管干预措施与 DID（每 10 万居民和日的 DDD 配药数量）和发病率的立即显著下降水平相关。干预措施实施后 12 个月，DID 比预期减少了 70%。这一数值在发病率方面为 59%。然而，未观察到斜率的变化，并且在研究期间的最后一段，使用开始再次上升。
尽管 RMM 对 UPA 的使用有立即的强烈影响，但长期来看，最后一段向上的趋势可能受到缺乏可比治疗选择的影响。应进一步开展研究，以确认观察到的上升趋势，并分析随后的措施和其他数据。
