title: 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 <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.
authors.affiliation: Washington University in St. Louis, Washington University School of Medicine, Adult Epilepsy Center, 660 S Euclid Ave., Campus Box 811, St. Louis, MO, USA. Electronic address: hogane@neuro.wustl.edu.
authors.forename: R Edward
authors.initials: RE
authors.lastname: Hogan
authors.affiliation: The Chaim Sheba Medical Center, Charles Clore Hospitalization Tower, East Wing, Tel Hashomer, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Blatt
authors.affiliation: Hospital Dr. Sótero del Río, Oficina de Investigaciones Médicas, Puente Alto, Chile.
authors.forename: Balduin
authors.initials: B
authors.lastname: Lawson
authors.affiliation: Neurological Clinic of Texas, 12221 Merit Dr., Suite 350, Dallas, TX, USA.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Nagaraddi
authors.affiliation: Bluegrass Epilepsy Research, 1401 Harrodsburg Rd B280, Lexington, KY, USA.
authors.forename: Toufic A
authors.initials: TA
authors.lastname: Fakhoury
authors.affiliation: Upsher-Smith Laboratories, Inc., 6701 Evenstad Drive, Maple Grove, MN, USA.
authors.forename: Bob
authors.initials: B
authors.lastname: Anders
authors.affiliation: Upsher-Smith Laboratories, Inc., 6701 Evenstad Drive, Maple Grove, MN, USA.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Clark
authors.affiliation: Upsher-Smith Laboratories, Inc., 6701 Evenstad Drive, Maple Grove, MN, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Laine
authors.affiliation: Upsher-Smith Laboratories, Inc., 6701 Evenstad Drive, Maple Grove, MN, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Halvorsen
authors.affiliation: Barrow Neurological Institute, 500 West Thomas Road, Suite 300, Phoenix, AZ, USA.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004351:Drug Resistance; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012640:Seizures / Q000188:drug therapy; D000077236:Topiramate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D000077236:Topiramate; D005632:Fructose
keywords: Antiepileptic drugs; Drug resistance; Extended-release; Partial seizures; Topiramate