IRCCS Istituto delle Scienze Neurologiche di Bologna, full member of the European Reference Network EpiCARE, Bologna, Italy.
IRCCS Istituto delle Scienze Neurologiche di Bologna, Epidemiology and Statistics Unit, Bologna, Italy.
Epilepsia. 2023 Apr;64(4):910-918. doi: 10.1111/epi.17526. Epub 2023 Feb 20.
Due to significant risks to the offspring after intrauterine exposure, the European Medicines Agency issued recommendations in 2014 and 2018 restricting the use of valproate (VPA) in women of childbearing age (WOCA). We aimed to evaluate their impact in the Emilia-Romagna region (ERR) of Northern Italy.
Using administrative databases, we identified all the ERR residents who received antiseizure medication (ASM) prescriptions from 2010 to 2020. Time series of incidence rates by sex and age group were evaluated for all ASMs. Focusing on VPA, an interrupted time series analysis was applied to assess the impact of the restrictions in WOCA with epilepsy (WOCA-E) and WOCA with psychiatric disorders (WOCA-P). We then evaluated the chronological order of ASM prescriptions with regard to the position of VPA.
Incidence rates of VPA prescriptions overall decreased over time. A significant decrease was observed only for females. The effect was stronger for WOCA, after both the first (incidence rate ratio [IRR] = .85, 95% confidence interval [CI] = .75-.96) and the second restriction (IRR = .67, 95% CI = .55-.82). The decrease was significant after the second restriction both for WOCA-E (IRR = .43, 95% CI = .27-.68) and for WOCA-P (IRR = .49, 95% CI = .35-.70), as well as VPA as a first prescription in both populations. VPA prescriptions as further choice did not show the same trend.
After the regulatory restrictions, an overall significant decline in the use of VPA in WOCA was observed in ERR. The second restriction has been effective in consolidating the prescription trend. However, VPA appears still to be a commonly used drug in WOCA when other ASMs have failed.
由于宫内暴露对子代有重大风险，欧洲药品管理局分别于 2014 年和 2018 年发布建议，限制育龄妇女（WOCAs）使用丙戊酸（VPA）。我们旨在评估这些建议在意大利北部艾米利亚-罗马涅地区（ERR）的影响。
我们使用行政数据库，确定了 2010 年至 2020 年期间从ERR 居民处获得抗癫痫药物（ASM）处方的所有患者。评估了所有 ASM 按性别和年龄组划分的发病率时间序列。针对 VPA，采用中断时间序列分析评估了对癫痫（WOCA-E）和精神障碍（WOCA-P）WOCAs 中限制 VPA 用药的影响。然后，我们评估了 VPA 处方的时间顺序与 VPA 位置的关系。
总体而言，VPA 处方的发病率随时间呈下降趋势。仅观察到女性的下降具有统计学意义。对于 WOCAs，在第一次（发病率比 [IRR] = 0.85，95%置信区间 [CI] = 0.75-0.96）和第二次限制（IRR = 0.67，95%CI = 0.55-0.82）之后，效果更强。第二次限制后，WOCA-E（IRR = 0.43，95%CI = 0.27-0.68）和 WOCA-P（IRR = 0.49，95%CI = 0.35-0.70）的发病率下降均具有统计学意义，VPA 作为这两种人群的一线处方也同样如此。VPA 作为二线处方并未显示出相同的趋势。
在监管限制之后，ERR 中 WOCAs 中 VPA 的总体使用量明显下降。第二次限制已有效巩固了处方趋势。然而，当其他 ASM 治疗失败时，VPA 似乎仍然是 WOCAs 中常用的药物。
