TOPIRAMATE AS FIRST-LINE THERAPY IN NEWLY DIAGNOSED EPILEPSY CHARACTERIZED BY PARTIAL-ONSET OR PRIMARY GENERALIZED TONIC-CLONIC SEIZURES
Abstract number :
2.284
Submission category :
Year :
2003
Submission ID :
652
Source :
www.aesnet.org
Presentation date :
12/6/2003 12:00:00 AM
Published date :
Dec 1, 2003, 06:00 AM
Authors :
James W. Wheless, Santiago Arroyo, Liza Squires, Roy E. Twyman, Steven Wang Department of Neurology, University of Texas, Houston, TX; Medical College of Wisconsin, Milwaukee, WI; Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ
Seizure type often determines the selection of an antiepileptic drug (AED). In newly diagnosed epilepsy, available data for classification of seizure type/epilepsy syndrome are often limited to patient/witness description of a low number of events, patient history, and interictal EEG. Being effective in both partial-onset and generalized seizures and less likely to aggravate seizures, broad-spectrum AEDs such as topiramate (TPM) are especially useful when epilepsy first emerges and clinical information for accurately classifying seizure type/syndrome is limited. A recently completed double-blind study compared 50 and 400 mg/day TPM as first-line therapy in 470 patients; we report the results for patient subsets defined by baseline seizure type.
Adults and children ([ge]25 kg) in whom an epilepsy diagnosis had been confirmed [le]3 months before study entry (or who had relapsed while off AEDs) and who had 1 or 2 partial-onset (POS) or primary generalized tonic-clonic (GTCS) seizures in a 3-month retrospective baseline were randomized to 50 or 400 mg/day TPM. Patients continued double-blind treatment until the first POS or GTCS or 6 months after the last patient was randomized.
470 patients entered double-blind treatment; 32% were children/adolescents (6-15 yrs of age). Of 234 patients randomized to TPM 50, 57% (N=133) had POS in baseline; 43% (N=101) had GTCS. 58% (N=138) of 236 patients randomized to TPM 400 had baseline POS; 42% (N=98) had GTCS. With epilepsy having been diagnosed 1 mo (median) before study entry, syndromes were not identified for the majority of patients. Median treatment duration: TPM 50, 266 days; TPM 400, 267 days. Time to 1st seizure showed a statistically significant difference favoring TPM 400 vs. TPM 50 for both POS (P=0.009) and GTCS (P=0.005). Based on Kaplan-Maier analyses, 6-mo seizure-free rates in patients with POS were 67% in the TPM 50 group and 82% in the TPM 400 group (P=0.012); 1-yr seizure-free rates were 56% and 71% (P=0.02). 6-mo seizure-free rates in patients with GTCS were 76% in the TPM 50 group and 85% in the TPM 400 group (P=0.156); 1-yr seizure-free rates were 63% and 81% (P=0.006). Adverse events (AEs) were qualitatively and quantitatively similar across seizure types. Discontinuations due to AEs were higher with TPM 400 vs. TPM 50 (POS: 18% vs. 8%; GTCS: 15% vs. 3%).
As in other AED studies, the probability of being seizure-free was somewhat higher for GTCS than for POS. In patients with previously untreated epilepsy, TPM monotherapy is highly effective against both POS and GTCS, consistent with its profile as a broad-spectrum AED.
[Supported by: Johnson [amp] Johnson Pharmaceutical Research [amp] Development]