Time course of 75%-100% efficacy response of adjunctive brivaracetam

Pavel Klein, Cédric Laloyaux, Sami Elmoufti, Teresa Gasalla, Melinda S Martin, Pavel Klein, Cédric Laloyaux, Sami Elmoufti, Teresa Gasalla, Melinda S Martin

Abstract

Background: Time to sustained seizure frequency reduction can provide clinically meaningful epilepsy outcomes.

Aims of the study: To examine the time course of brivaracetam (BRV) efficacy in adults with focal seizures and focal to bilateral tonic-clonic seizures (FBTCS).

Methods: Post hoc analysis of data pooled from three randomized controlled trials of oral adjunctive BRV in adults with epilepsy. Patients with focal epilepsy and a subpopulation with FBTCS receiving BRV 50, 100, or 200 mg/d (initiated without up-titration) or placebo for 12 weeks were analyzed for time to sustained ≥75%, ≥90%, and 100% seizure reduction without interruption from first day until trial ends.

Results: Evaluation included 1160 patients with focal seizures, including 352 patients with FBTCS. Sustained ≥75%, ≥90%, and 100% response in focal seizures was higher from day 1 for BRV 100 and 200 mg/d vs placebo (P < .01). Sustained ≥75% and 100% FBTCS reduction from day 1 was higher for BRV 100 and 200-mg/d groups vs placebo (P < .01).

Conclusions: The majority of patients achieving 75%-100% sustained seizure frequency reduction (all focal seizure types and the subpopulation with FBTCS) with oral BRV (100 or 200 mg/d) achieved this response on the first-treatment day.

Keywords: antiepileptic drugs; focal epilepsy; focal to bilateral tonic-clonic seizures; partial-onset seizures; sustained seizure reduction.

Conflict of interest statement

P. Klein has served as a consultant for Abbott, SK Life Science and Neurelis, a speaker for Sunovion, a consultant, advisory board member, and speaker for Aquestive, Eisai, and UCB Pharma, is a member of the Medical Advisory Board of Alliance and of the Scientific Advisory Board of OB Pharma, and has received research support from Lundbeck, and from CURE/Department of Defense. C. Laloyaux, S. Elmoufti, T. Gasalla, and M. S. Martin are employees of UCB Pharma.

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
Kaplan‐Meier estimates of time to onset of sustained response in patients with focal seizures from treatment day 1 through treatment day 84. A, Sustained ≥75% responder status. For each day, P < .01 for BRV 100 and 200 mg/d vs placebo; P < .05 at days 16‐48 and 74‐84 for the BRV 50‐mg/d group. B, Sustained ≥90% responder status. For each day, P < .01 for BRV 100 and 200 mg/d vs placebo; P < .05 at days 42‐51 and 59‐62 for the BRV 50‐mg/d group. C, Sustained 100% responder status. For each day, P < .05 for BRV 50 mg/d, and P < .01 for BRV 100 and 200 mg/d, vs placebo. Analyses performed on the efficacy population. 5 BRV, brivaracetam
FIGURE 2
FIGURE 2
Percentage of patients attaining sustained response (at treatment day 1) by number of all prior AEDs. A, Sustained ≥75% response and B, sustained ≥90% response. In each trial, prior AEDs were discontinued before study entry. N01358 was the only trial capturing all history of prior AEDs used before entry; N01252 and N01253 collected AED use within 5 y before study entry and were not included. Analyses performed on efficacy population. 5 AED, antiepileptic drug; BRV, brivaracetam
FIGURE 3
FIGURE 3
Kaplan‐Meier estimates of time to onset of sustained response in patients with FBTCS from treatment day 1 through treatment day 84. A, Sustained ≥75% responder status. For each day, P < .01 for BRV 100 and 200 mg/d vs placebo; P‐values were not significant (NS) for BRV 50 mg/d vs placebo. B, Sustained ≥90% responder status. For each day, P < .01 for BRV 100 and 200 mg/d vs placebo; P‐values were NS for BRV 50 mg/d vs placebo. C, Sustained 100% responder status. For each day, P < .01 for BRV 100 and 200 mg/d vs placebo; P‐values were NS for BRV 50 mg/d vs placebo. Analyses performed on efficacy population. 5 BRV, brivaracetam; FBTCS, focal to bilateral tonic‐clonic seizures

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