Abstracts

RATIONALE: Most data regarding impact of new antiepileptic drugs is derived from randomized placebo-controlled trials of short duration. However it is also important to assess the potential for long-term benefit from these agents. Zonisamide (ZNS) regulatory trials were initiated up to 16 years prior to FDA approval. From these, patients entered long-term follow-up studies, during which seizure calendars and adverse event data were rigorously captured.
Objective: To assess the long-term therapeutic effects of ZNS by evaluating results from long-term extension studies
METHODS: After completion of regulatory trials with ZNS, patients were eligible to enroll in one of 3 long-term extension studies in Europe and the US. Criteria for enrollment in the original trials included history of treatment refractory partial seizures. During long-term extension medications could be added or eliminated. Monthly seizure calendars were rigorously maintained by patients and retrieved at quarterly study visits. Seizure data was maintained in a centralized database. Seizure frequency was assessed during the last 3 months of ZNS therapy, regardless of whether patients discontinued. This was compared to seizure rate at baseline, and at the time they initially attained their target dose, to determine whether tachyphylaxis occurred.
RESULTS: 381 patients entered extension studies. Data available from these patients included demographics, discontinuation (d/c) rates and reason for d/c. One European study was excluded from seizure outcome analysis, because substantial seizure data was missing. Therefore, 251/381 patients were eligible for analysis of seizure frequency over time. Mean duration of epilepsy prior to ZNS was 21.8 years. Median baseline seizure frequency was 9/month. Including those that d/c[ssquote]d, mean duration of ZNS therapy was 2.9 years (range .2-16).Retention rate after 4.5 years of therapy was 28%. 142/381 (37%) patients were on fewer concomitant AEDs at the end of ZNS exposure than at baseline. 54 were on ZNS monotherapy for a mean of 671 days. Specific reasons for d/c included adverse events in 13.7%, and lack of efficacy in 37.2%.
Seizure analysis (N=251): There was a median 38% reduction in seizures from baseline once target dose was reached. At the time of last evaluation (including patients who discontinued) there had been a median 61% partial seizure reduction from baseline. Of pts who d/c[ssquote]d, only 13% had an increase in seizures in the last 3 months of ZNS rx compared to baseline. Of those remaining on ZNS, 30 were seizure free at the last evaluation (11.3% of cohort).
CONCLUSIONS: ZNS is effective as long-term therapy. There is no evidence of tachyphylaxis. With long-term exposure, there appears to be a continued reduction in seizure frequency over time.
Objective: at the end of this presentation, individuals should be able to discuss long-term outcome with zonisamide use
[Supported by: Elan Pharma]; (Disclosure: Grant - Elan Pharma, Consulting - Elan Pharma, Honoraria - Elan Pharma, Other - Alissa Ruelle is an employee of statprobe. Statprobe was hired to perform statistics on this data set.)