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Topiramate Monotherapy Appears to Offer Substantial Seizure Reduction in Patients with Epilepsy: Presented at EFNS

By Chris Berrie

BRUSSELS, BELGIUM -- August 27, 2007 -- Topiramate, a broad-spectrum anticonvulsant, was well tolerated and associated with a substantial reduction in seizure frequency and a high seizure-free rate in patients with epilepsy who were not responsive to valproic acid (VPA), another broad-spectrum anticonvulsant, say researchers.

Speaking at the 11th Congress of the European Federation of Neurological Societies (EFNS) on August 26th, Barbara Schauble, MD, Principal Investigator and Germany Medical Development Manager (Neurology), Medical and Scientific Affairs EMEA, Janssen-Cilag, Neuss, Germany, pointed out that VPA is a highly effective first-line medication against generalised seizures and partial epilepsies. However, many patients show substantial adverse effects, including weight gain, tremors, somnolence, insulin resistance and hepatopathy.

As topiramate has recently been demonstrated to be effective and well tolerated as monotherapy for treatment of seizures, the aim of this multicentre, open-label, single-arm, non-interventional study was to explore in the setting of neurological practices and outpatients clinics in Germany the effectiveness and tolerability of topiramate after prior treatment with VPA.

Patients in the study had to be over 12 years of age with any seizure type or epilepsy syndrome who were switched from VPA to topiramate due to insufficient effectiveness and/or insufficient tolerability with VPA.

The 147 patients (mean age, 42 years; male, 41%) were assessed at baseline, with primary outcomes of effectiveness (seizure frequency, compared to 12-week retrospective baseline) and tolerability of topiramate, followed to 20 weeks. The secondary outcomes were treatment effectiveness as seizure reductions and responder rates. The safety assessment monitored patient vital signs and body weight, along with treatment-emergent/ related adverse events (AEs).

Insufficient effectiveness of previous VPA therapy was seen in 61% of these patients, with 81% having shown side effects that related to weight gain (37%), tremor (29%), somnolence (21%) and cognition (10%).

The baseline clinical characteristics showed their mean duration of epilepsy as 9 years, with a median of 2 previous AED treatments. During the 12-week retrospective baseline, 77% of these patients had seizures, with the most common seizure types of generalised tonic-clonic (52%), complex partial (23%), simple partial (12%) and absence (10%); the median number of all-type seizures during this period was 1.3/month.

At first administration of topiramate, the mean dose of VPA was 1,286 mg, and the mean topiramate dose at study endpoint of 125 mg/day comprised 12.9% of patients at less than 50 mg/day, 36.7% at 75 to 100, 15.0% at 125 to 150, 24.5% at 175 to 200, and 10.9% at greater than 200 mg/day.

The mean seizure frequency was significantly reduced during the maintenance stage to 3 per month, from the baseline of 32 per month (P <.0001), with 94% of seizure-free patients during baseline remaining seizure-free throughout the study.

The ratings for the physicians' global assessments for tolerability (very good, good) and for improvements (a little/ much better) as compared to baseline were in favour of topiramate use (83%, 79%, respectively), as were physician and patient assessments of the treatment switch (86%, 80%, respectively).

The only treatment-related AEs (total, 14.3%) seen in 3% or more of patients were weight decrease (4.8%) and paraesthesia (4.2%), with speech disorder seen in only 2.7%; furthermore, only 8% of patients withdrew due to an AE and 3% due to insufficient effectiveness of topiramate treatment.

Dr Schauble said, "The main message is that switching the patients to topiramate was associated with a very substantial seizure reduction, seizure-free patients, and an excellent tolerability profile, with many of these patients actually receiving topiramate monotherapy at a dose of around 100 to 150 mg [per day]."

Dr Schauble added, "We have also been examining patients on other anticonvulsants and looking at what happens with them when they switch onto topiramate monotherapy, and we were able to see substantial seizure reductions not only with valproic acid, but also with carbamazepine, oxcarbamazepine and even phenytoin pre-treatment, which was associated also with a very good tolerability profile."

The study was sponsored by Janssen-Cilag.

[Presentation title: Effectiveness of topiramate in patients with epilepsy transitioning from valproic acid – Results from an open-label, non-interventional trial. Abstract P1229]

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