Abstracts

RATIONALE: Initial double-blind placebo-controlled trials of topiramate (TPM) in adult patients with refractory epilepsy evaluated dosages of 400-1,000 mg/day. Recent data and postmarketing experience suggest that [lte]200 mg/day add-on is an effective and well tolerated dose. In this observational study the efficacy and tolerability of TPM add-on was evaluated in patients with epilepsy allowing flexible dosing. We report the results of patients receiving [lte] 200 mg TPM/day compared to those with higher doses.
METHODS: In this prospective multicenter observational study patients [gte] 16 years of age were evaluated at baseline and 4, 8, 12 and 26 weeks thereafter. Seizure frequency and adverse events (AEs) were assessed at every visit. Dosages of TPM and concomitant AEDs could be adjusted according to patient response.
RESULTS: 574 patients (54% male, mean age 39 [plusminus] 13 years, median time since diagnosis 13 years, [gt]80% partial epilepsy) completed the 26 weeks observational period: n = 282 received [lte]200 mg (mean dose 160 [plusminus] 52 mg/day, group [A]) and n = 292 more than 200 mg TPM/day (mean dose 380 [plusminus] 110 mg/day, group [B]). Both groups were comparable in demographics and epilepsy history. Baseline seizure frequency was 4/months in [A] and 6/month in [B] (p[lt]0.001). At endpoint, median seizure reduction was 80% [A] and 67% [B] (p[lt]0.0001 vs. baseline each, p=0.005 between groups). Responder rates ([gte]50% reduction in seizure frequency) were 71.3% and 68.9%, with 25.6% of the patients in [A] and 9.8% in [B] remaining seizure free for [gte]3 months (p[lt]0.001). Interestingly, there was no significant difference in total AEs (27.0% [A] and 27.1% [B]). AEs reported by [gte]5% of the patients were somnolence (8.2% and 5.8%), dizziness (5.1% and 5.0%) and weight loss (6.4% and 4.8%) for groups A and B, respectively. Mean weight reduction at 6 months was similar in both groups (2.0 [plusminus] 4.4 kg [A] and 1.6 [plusminus] 4.6 kg [B], n.s.).
CONCLUSIONS: In this large patient population topiramate add-on showed significant efficacy in dosages both [lte] 200 and [gt] 200 mg/day. Individual dosing of TPM and adjustment of concomitant AEDs in this study seems to contribute to the good tolerability and to the fact that we did not observe significant differences in tolerability with higher doses of topiramate as add-on therapy
[Supported by: This study was funded by Janssen-Cilag Germany.]; (Disclosure: Salary - Andreas Schreiner is a full-time employee of Janssen-Cilag Germany.)