Impact of recommendations on sodium valproate prescription among women with epilepsy: An interrupted time-series study

Adeline Degremont (1, 2) , Elisabeth Polard (2, 1) , Sandrine Kerbrat (2) , Olivier Grimaud (3, 4, 2) , Annie-Pierre Jonville-Béra (5) , Virginie Ringa (6) , David Travers (1) , Emmanuel Oger (2, 1) , Arnaud Biraben (7) , Emmanuel Nowak (8, 9)

1 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
2 REPERES - Recherche en Pharmaco-épidémiologie et Recours aux Soins
3 EHESP - École des Hautes Études en Santé Publique [EHESP]
4 METIS - Département Méthodes quantitatives en santé publique
5 CHU Trousseau [Tours]
6 CESP - Centre de recherche en épidémiologie et santé des populations
7 LTSI - Laboratoire Traitement du Signal et de l'Image
8 SCINBIOS - Sciences et ingénierie en biologie santé
9 CIC Brest

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Mots clés: Epilepsy; Interrupted time series; Regulatory actions; Trend; Valproate

Domaines: Sciences du Vivant [q-bio]

Adeline Degremont, Elisabeth Polard, Sandrine Kerbrat, Olivier Grimaud, Annie-Pierre Jonville-Béra, et al.. Impact of recommendations on sodium valproate prescription among women with epilepsy: An interrupted time-series study. Epilepsy & Behavior, 2021, 125, pp.108449. ⟨10.1016/j.yebeh.2021.108449⟩. ⟨hal-03468475⟩