Effectiveness of risk minimisation measures for valproate: A drug utilisation study in Europe

Abstract

Purpose The purpose of this study was to evaluate the effectiveness of the risk minimisation measures (RMMs) implemented in Europe in 2014 for valproate‐containing products to mitigate their risk during pregnancy and to characterise valproate prescribing patterns in women of childbearing potential (WCBP) before and after implementation of RMMs. Methods A multinational cohort study based on existing data sources using a pre‐/post‐ design was performed in five European countries (France, Germany, Spain, Sweden, UK) in an outpatient setting. Effectiveness of RMMs was assessed by comparing the proportion of valproate initiations as second (or subsequent) line therapy before and after implementation of RMMs (primary outcome) with an increase in this proportion indicating success of RMMs. Overall use of valproate and incidence of pregnancies in WCBP were also examined. Results The proportion of valproate initiations as second line therapy increased after implementation of RMMs in incident female users in Sweden (from 81.1%, 95% CI 79.9%‐82.3% to 84.5%, 95% CI 83.5%‐85.5%) and the UK (from 66.4%, 95% CI 64.5%‐68.3% to 72.4%, 95% CI 70.0%‐74.9%), it remained the same in Germany and Spain and decreased in France from 48.7% (95% CI 45.6%‐51.9%) to 40.6% (95% CI 37.6%‐43.7%). In Sweden and the UK, the incidence of pregnancies exposed to valproate decreased in the post‐implementation period: 8.0 vs 9.5 and 10.9 vs 16.9 per 1000 person‐years, respectively. Conclusion The results on primary outcome of this study suggest limited effectiveness of the RMMs. Additional RMMs were implemented in 2018.

Valproate utilisation trends among women of childbearing potential in Ireland between 2014 and 2019: A drug utilisation study using interrupted time series

“…29 In addition, a recent drug utilisation study examined valproate prescribing patterns in five European countries (France, Germany, Spain, Sweden and the UK) and found that, in all countries, the proportion of WCBP prescribed valproate had decreased (between 30.1% and 52.3%) following the 2014 intervention. 30 Similarly, our study identified an overall decline in the month-to-month use of valproate among WCBP (16-44 years) following the 2014 EMA intervention.…”

“…These patterns observed, support our recent survey study findings from the Irish HCP setting, which found that all responding neurologists reported that they had considered an alternative treatment before initiating their patient on valproate 29 . In addition, a recent drug utilisation study examined valproate prescribing patterns in five European countries (France, Germany, Spain, Sweden and the UK) and found that, in all countries, the proportion of WCBP prescribed valproate had decreased (between 30.1% and 52.3%) following the 2014 intervention 30 . Similarly, our study identified an overall decline in the month‐to‐month use of valproate among WCBP (16–44 years) following the 2014 EMA intervention.…”

Characterization of pregnancies among women with epilepsy using valproate before or during pregnancy – A longitudinal claims data analysis from Germany

“…Despite these positive trends, there are studies supporting our impression that the use of alternative drugs before valproate initiation is still suboptimal in Germany. A study assessing the proportion of women with newly diagnosed epilepsy using valproate as second-line rather than first-line therapy in various European countries--before and after implementation of risk minimization measures--did not observe a change in Germany, while the proportion increased in Sweden, the UK, and Spain (Toussi et al, 2021b). The same study also investigated changes in the incidence of valproate-exposed pregnancies, but for this part of the analysis, no data from Germany were available.…”

Measures to Mitigate Sodium Valproate Use in Pregnant Women With Epilepsy

“…On these grounds, the European Medical Association introduced extra measures to enforce the previous restrictions. Further studies are underway to determine the effectiveness of the new measures and to monitor valproate use in women with childbearing potential and pregnancies exposed to it [36].…”