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

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.