Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, CHU de Rennes, 35033 Rennes, France; Univ Rennes, EA 7449 REPERES 'Pharmacoepidemiology and Health Services Research', 35000 Rennes, France.
Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Department of Clinical Pharmacology, CHU de Rennes, 35033 Rennes, France; Univ Rennes, EA 7449 REPERES 'Pharmacoepidemiology and Health Services Research', 35000 Rennes, France.
Epilepsy Behav. 2021 Dec;125:108449. doi: 10.1016/j.yebeh.2021.108449. Epub 2021 Nov 25.
The European Medicines Agency (EMA) has developed risk minimization measures (RMMs) to reduce the use of the teratogenic drug, sodium valproate (VPA). The objective was to assess the impact of these RMMs among females with epilepsy in France.
We used data from the French National Health Insurance Database (SNDS), including 114,936 females aged under 50, with a reimbursement claim for an antiepileptic drug from January 2011 to December 2017, and identified as people with epilepsy. We used a controlled interrupted time series stratifying on age: girls (0-14 years old) and women of childbearing age (15-49 years), and with 129,917 males as controls.
VPA prevalent use among girls and women of childbearing age with epilepsy decreased significantly after the issue of the RMMs (trend changes of, respectively, -5 and -4 users per 1000 females at-risk per quarter in comparison to the control group). We did not detect any significant change in VPA incident use.
VPA use decreased over the study period among females with epilepsy but there were still 317 women and 206 girls started on VPA therapy VPA in 2017 (8 per 1000 at-risk and 18 per 1000, respectively). This suggests that either the measures should be strengthened or that the lowest level of VPA use has been reached. In this context, the introduction of a new RMM (in 2018) needs to be evaluated.
欧洲药品管理局(EMA)已制定风险最小化措施(RMM)以减少致畸药物丙戊酸钠(VPA)的使用。目的是评估这些 RMM 在法国癫痫女性中的影响。
我们使用了来自法国国家健康保险数据库(SNDS)的数据,包括 114936 名年龄在 50 岁以下、2011 年 1 月至 2017 年 12 月有抗癫痫药物报销索赔记录的女性,她们被确定为癫痫患者。我们按照年龄进行了分层的对照中断时间序列分析:女孩(0-14 岁)和生育年龄的妇女(15-49 岁),并以 129917 名男性作为对照。
在 RMM 发布后,癫痫女孩和生育年龄妇女中 VPA 的普遍使用显著下降(与对照组相比,每季度每 1000 名高危女性分别减少了 5 名和 4 名使用者)。我们没有发现 VPA 新发病例使用的任何显著变化。
在研究期间,癫痫女性中 VPA 的使用有所减少,但在 2017 年仍有 317 名妇女和 206 名女孩开始使用 VPA 治疗(每 1000 名高危女性中有 8 名和每 1000 名高危女性中有 18 名)。这表明,要么应加强这些措施,要么已经达到了 VPA 使用的最低水平。在这种情况下,需要评估新的 RMM(2018 年)的引入。