Abstracts

Rationale: Zonisamide is an antiepileptic drug (AED) approved in Europe as an add-on treatment of adult patients with partial seizures, with or without secondary generalization. Several post-marketing observational studies on zonisamide have been conducted in different European countries: France, Germany, Spain, Nordic countries (Denmark, Finland, Norway and Sweden), UK, and Italy. The objective of this study is to propose a methodology allowing the pooling of data from these different European observational studies performed on zonisamide. The aim is to describe the zonisamide intake, in particular the dosing regimen, and the duration of treatment, in routine clinical practice, for patients with partial epilepsy. Secondary objectives are to assess the efficacy and tolerance of zonisamide.Methods: Five of the 7 studies are available to carry out the analysis: Ozone (France), ZADE (Germany), Ezone-Galicia study (Spain), ZENIT (Nordic countries) and an observational study from the UK. As none of these studies have been performed exactly with the same methodology (design, duration of follow-up, eligibility criteria...), it has been decided to conduct a pooled analysis of patient-level data. A definition of specific inclusion criteria related to the analysis will be required to homogenize the study population, in particular in terms of age, type and severity of epilepsy. Special attention will be paid to find common endpoints.Results: These studies will provide a data pool from a total of around 1000 patients: 428, 365, 203, 150 and 33 patients from studies from France, Germany, UK, Nordic countries and Spain respectively. In view of designs and gathered data of the studies, the dosing regimen will be described regarding maintenance dose attained and the duration of treatment regarding the time between the initiation of treatment and the end of follow-up or the date of discontinuation. The efficacy of zonisamide will be assessed (overall and by study) in terms of proportion of seizure-free patients in the last month, and potentially in the last two and three months, and proportion of responders (patients with a decrease by at least 50% in monthly seizure frequency compared to the start of zonisamide). Tolerability of zonisamide will be evaluated regarding adverse events (especially psychiatric and metabolic or nutrition disorders and.weight loss) Statistical models will allow us to consider different variables as age, gender and study (because of heterogeneity between designs). Subgroup analyses will be carried out, such as an analysis of AED combinations (zonisamide with other AEDs, among levetiracetam, lamotrigine, valproic acid, carbamazepine or topiramate). Conclusions: This pooled analysis of patient-level data should allow a new insight of zonisamide in routine clinical practice, in terms of dosing regimen and duration of treatment, and an assessment of the efficacy and tolerability with a higher number of patients. Improving the statistical power, this analysis should also allow subgroup analyses such as the assessment of efficacy of zonisamide in AED combinations