Abstracts

Rationale: New Options are urgently needed in the treatment of Lennox-Gastaut-Syndrom (LGS). Since June 2007 rufinamide is available in Germany as adjunctice therapy in LGS. We report our experiences with rufinamide with respect to effectiveness and tolerability in the context of polytherapy over 4 years. Methods: Up to May 2011 114 adults were treated with rufinamide (age 18-68 years, mean 34,7 years, 52 men) on an open label, combined in- and out-patient base. All patients suffered from pharmacoresistant epilepsies and frequent seizures (45 patients with daily seizures), 75 patients suffered from LGS. 95 patients had antiepileptic polytherapy (2-4 AEDs, mean 2,5 AEDs) previous to the administration of rufinamide. 31 patients had a Vagal Nerve Stimulator (VNS). Rufinamide was titrated slowly (+200mg/3-7 days, target 500-3600mg/day, median 1800mg/day) Results: Responder rate was 14%/21%/33% after 6/12/24 months respectively. We saw worsening of seizures in one case (withdrawal after 3 months). In 20/114 patients (18%) side effects (toxic cerebellar syndrome, sedation) occurred. In 9 cases rufinamide had to be discontinued due to side effects. In the other cases side effects were intraindividually dose-dependent (not interindividually) and could be abolished either by reduction of co-medication or rufinamide. Retention rate was 77% (73/94) after 6 months, 62% (58/94) after12 months and 36% (34/94) patients are still were on rufinamide after 2 years. There was a trend towards better long term effectiveness in the non-LGS-group compared to the LGS-group: 5/10 (50%) responders vs. 7/24 (29%) respectively. Conclusions: Rufinamide is well tolerated even in complex polytherapy, pharmacokinetic interactions are insignificant. Side effects seemed to be related to individual doses and cumulative pharmacodynamic phenomena in polytherapy. Influence on seizure frequency is limited and freedom of seizures could not be achieved - a result not unexpected in LGS. But several worthwhile effects were observed, as well in syndromes closely related to LGS. Our experiences confirm earlier results of studies in children and adolescents with respect to effectiveness and retention rate (Glauser et al. 2008, Kluger et al. 2010). Tolerability was better in our group (sedation 9% and vomiting 10% vs. 24,3% and 21,6% respectively) compared to pivotal studies (Glauser et al. 2008) and was similar to the results of Kluger et al.. This effect may be induced by slower titration. Our data suggest a broad activity of rufinamide not only in LGS, but as well in related syndromes of (multi-)focal epilepsies with encephalopathy. Our results in a sample of adult patients do not significantly differ from those in children and adolescents published by other investigators. Further investigations are necessary to assess the role of rufinamide in the treatment of different epilepsy syndromes.