Efficacy of once-daily extended-release topiramate (USL255): A subgroup analysis based on the level of treatment resistance

Abstract

Results from a previously conducted global phase III study (PREVAIL; NCT01142193) demonstrate the safety and efficacy of once-daily USL255, Qudexy™ XR (topiramate) extended-release capsules, as adjunctive treatment of drug-resistant partial-onset seizures (POSs). In this study, we report a post hoc analysis of PREVAIL data according to patient level of treatment resistance (based upon the number of concomitant antiepileptic drugs [AEDs] and lifetime AEDs) at baseline, with patients defined as either having "highly" drug-resistant seizures (≥2 concurrent AEDs and ≥4 lifetime AEDs) or having "less" drug-resistant seizures (1 concurrent AED or b 4 lifetime AEDs) at baseline. For each subgroup, median percent reduction in POS frequency (primary endpoint), responder rate, Clinical Global Impression of Change (CGI-C), and Quality of Life in Epilepsy -Problems (QOLIE-31-P) survey were assessed. Of 249 PREVAIL patients, 115 were classified as having highly drug-resistant seizures (USL255: n = 52, placebo: n = 63), and 134 were classified as having less drug-resistant seizures (USL255: n = 72, placebo: n = 62) at baseline. For the primary endpoint, USL255 resulted in significantly better seizure outcomes compared with placebo regardless of drug-resistant status (P = .004 and P = .040 for "highly" and "less", respectively). Responder rate was also significantly improved in patients with highly drug-resistant group (P = .023). The CGI-C scores indicated significant improvement in both subgroups (P = .003 and P = .013 for "highly" and "less", respectively). On the QOLIE-31-P, a significant improvement on the seizure worry subscale for the group with less drug-resistant seizures was noted in USL255-treated patients compared with placebo-treated patients (P = .003); the overall score and all other subscales were not significantly different for both subgroups. We conclude that USL255 led to significant improvements across multiple outcomes compared with placebo, including in those classified as having highly drug-resistant seizures to prior treatment, making it a valuable treatment option for patients with epilepsy.

Predicting Response to Treatment of Epileptic Seizures: How Much Time and How Many AEDs Do We Need to Try?

“…2 This definition strongly relied on a study of a large cohort of patients from Glasgow, Scotland, which showed that after failure of 2 monotherapy AEDs, the chance of the use of a third drug to produce seizure freedom was <10%. 8 However, other studies show that patients respond favorably to >2 AED trials, 9,10 so the current study gives further evidence that persistence in treatment with AEDs, typically working with at least 4 AEDs over approximately 3 years, will yield positive results for patients.…”

Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures

“…In regard to the post hoc analysis of efficacy by drug refractoriness, the authors acknowledge that the International League Against Epilepsy (ILAE) definition of drug-resistant epilepsy ("failure of adequate trials of two tolerated and appropriately chosen and used AED schedules") [27] was not used, as the PREVAIL OLE study design prevents verification of patient participation in two "adequate trials". Therefore, the definition for drug resistance in the post hoc analyses was based on clinical experience and a pharmacoeconomic study that classified 'patients with refractory seizures' as those on three or more AEDs [12,28]. Despite the limitations of defining drug resistance, many patients responded favorably to addition of USL255.…”

“…Patients were also evaluated for seizure-free intervals (defined as the percentage of patients who were seizure-free for an interval of 4, 12, 24, 36, or 48 weeks at any time during the study). Based on a surrogate measure of drug refractoriness (the number of current and lifetime AEDs), patients were divided into two groups: patients with ≥2 concurrent AEDs and ≥4 lifetime AEDs were defined as having "highly" drug-resistant seizures, while the rest of the study population comprised the group of patients with "less" drugresistant seizures (one concurrent AED and/or b 4 lifetime AEDs) [12].…”

Епілепсія, Мігрень, Гіперкінези: Механізм-Індукована Симптоматична Терапія

“…На рис. 2 зображено ефективність застосування ад'ювантної терапії топіраматом у пацієнтів із фармакорезистентною епілепсією [21].…”