Effect of lifetime antiepileptic drug treatment history on efficacy and tolerability of adjunctive brivaracetam in adults with focal seizures: Post-hoc analysis of a randomized, placebo-controlled trial
Autor: | Pavel Klein, Sami Elmoufti, Xavier Nondonfaz, Richard S. McLachlan, Kathy Foris, Svetlana Dimova, Christian Brandt |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male medicine.medical_specialty Adolescent Placebo-controlled study Brivaracetam Placebo 03 medical and health sciences Epilepsy Young Adult 0302 clinical medicine Double-Blind Method Seizures Internal medicine medicine Humans Adverse effect business.industry Middle Aged medicine.disease Pyrrolidinones Discontinuation 030104 developmental biology Treatment Outcome Neurology Tolerability Concomitant Anticonvulsants Drug Therapy Combination Female Neurology (clinical) Epilepsies Partial business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Epilepsy research. 167 |
ISSN: | 1872-6844 |
Popis: | Objective To evaluate the efficacy and tolerability of adjunctive brivaracetam (BRV) in adults with focal seizures by the number of lifetime (previous and concomitant) antiepileptic drugs (AEDs). Methods Post-hoc analysis of data from N01358 (NCT01261325), a randomized, double-blind, placebo (PBO)-controlled Phase III trial evaluating BRV 100 and 200 mg/day in patients ≥16 years of age with uncontrolled focal seizures. Efficacy and tolerability outcomes were assessed for the 12-week Treatment Period in subgroups of patients with 1–2, 3–4, 5–6, or ≥7 lifetime AEDs. Results 764 patients received at least one dose of trial medication (BRV: 503; PBO: 261; Safety Set), of whom 14.3% had 1–2, 20.8% had 3–4, 21.3% had 5–6, and 43.6% had ≥7 lifetime AEDs. In all lifetime AED subgroups, >85% of patients completed the trial. Patients with a higher number of lifetime AEDs had a younger age at epilepsy onset, longer epilepsy duration, and higher baseline seizure frequency. In patients on BRV, 50% responder rates were 49.3%, 44.4%, 47.2% and 27.4% in patients with 1–2 (n = 75), 3–4 (n = 99), 5–6 (n = 108) and ≥7 (n = 219) lifetime AEDs; 75% responder rates were 36.0%, 21.2%, 22.2% and 12.3%. In patients on PBO, 50% responder rates were 35.3%, 25.9%, 20.4% and 15.9% in patients with 1–2 (n = 34), 3–4 (n = 58), 5–6 (n = 54) and ≥7 (n = 113) lifetime AEDs; 75% responder rates were 26.5%, 6.9%, 3.7% and 4.4%. The Kaplan-Meier estimated probability of patients achieving a sustained 50% or 75% response from the first day of treatment was generally higher in patients with a lower number of lifetime AEDs (both in patients on BRV and PBO). In patients on adjunctive BRV, the incidence of drug related treatment-emergent adverse events (TEAEs) was 34.7%, 26.0%, 44.4% and 47.7% in patients with 1–2 (n = 75), 3–4 (n = 100), 5–6 (n = 108) and ≥7 (n = 220) lifetime AEDs; the incidence of discontinuations due to TEAEs was 1.3%, 3.0%, 8.3% and 10.5%. Conclusions This post-hoc analysis suggests a numerically higher response to adjunctive BRV in patients with fewer lifetime AEDs. The lowest response was observed in patients with ≥7 lifetime AEDs, although these patients could also benefit from adjunctive BRV treatment. Patients with fewer lifetime AEDs had lower discontinuation of BRV due to TEAEs. |
Databáze: | OpenAIRE |
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