Outcomes of sustained-release formulation of valproate and topiramate monotherapy in patients with epilepsy: a multi-centre, cohort study

Abstract

Background: New-generation antiepileptic drugs (AEDs) tend to replace traditional AEDs as the first-line choice for epilepsy. However, whether this change results in better outcome, especially in China, remains unknown.

Methodology/principal findings: Two broad spectrum AEDs, the traditional drug of sustained-release formulation of valproate (SRVPA) and the new-generation drug of topiramate, were compared in patients with epilepsy as monotherapy in this multi-centre, observational cohort study from 2000 to 2011. The primary outcome was time to treatment failure. The secondary outcomes included time to first seizure, time to 12-month remission, and time to 24-month remission. Drug tolerability was assessed. Cox proportional hazard models (95% confidence interval [CI]) were used to analyse the relative risks expressed as hazard ratios (HR). Of the 1008 recruited patients, 519 received SRVPA and 489 received topiramate. SRVPA was better than topiramate (28.3% vs. 41.5%; HR = 0.62, [95% CI 0.49-0.77]; p<0.0001) in primary outcome, and in time to first seizure (56.1% vs. 69.3%; HR = 0.73, [95% CI 0.62-0.86]; p = 0.0002). No significant difference was observed between two groups in time to 12-month remission (52.6% vs. 42.5%; HR = 1.01, [95% CI 0.84-1.23]; p = 0.88) and time to 24-month remission (34.7% vs. 25.2%; HR = 1.11, [95% CI 0.88-1.42]; p = 0.38). 36 patients (6.9%) in SRVPA group and 37 patients (7.6%) in topiramate group presented treatment failure associated with intolerable adverse events, there was no significant difference between the two groups (p = 0.70).

Conclusions: The SRVPA is more suitable than topiramate for Chinese epileptic patients, and our results support the viewpoint that traditional AEDs should be the first-line choice for epilepsy rather than new-generation AEDs.

Figure 1. Study flow diagram.

Figure 2. Kaplan-Meier estimates of clinical outcomes.

A: Probability of non-treatment failure; B: Probability of non-first seizure; C: Probability of 12-month remission of seizures; D: Probability of 24-month remission of seizures.