Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: Second interim analysis of 6-month data from a prospective observational study in Europe

Steinhoff, Bernhard J.; Christensen, Jakob; Doherty, Colin P.; Majoie, Marian; Backer, Marc De; Hellot, Scarlett; Leunikava, Iryna; Leach, John Paul

doi:10.1016/j.eplepsyres.2020.106329

Cited by 18 publications

(33 citation statements)

References 17 publications

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“…In the cohort of patients included in the BRIVAFIRST who have a long disease duration, a considerable number of previously failed ASMs, and a high number of ongoing ASMs, the rates of seizure freedom and seizure response at 12-month follow-up were 16% and 37%, respectively. These figures indicate the efficacy of BRV to control seizures when added to the pre-existing therapeutic regimen in everyday clinical practice in patients with difficult-to-treat epilepsy, and confirm previous evidence [21][22][23][24][25][26][27][28]. In line with other ASMs [29,30], an inverse relationship between response to adjunctive BRV and the number of lifetime medications was observed, confirming that the higher the number of failed treatments, the lower the likelihood that the patient may benefit from subsequent interventions [31].…”

Section: Discussionsupporting

confidence: 83%

“…During the 1-year study period, the overall rate of treatment discontinuation was about 25%, which was similar to that observed in other studies focusing on BRV and newer ASMs in clinical practice, including eslicarbazepine, perampanel, and lacosamide [21][22][23][24][25][26][27][28][29][34][35][36]. The main reason for drug withdrawal was inadequate efficacy, and BRV was interrupted within the first 3 months of treatment in almost half of the cases.…”

Section: Discussionsupporting

confidence: 81%

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Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

et al. 2021

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Background In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drugresistant focal epilepsy. Studies performed in a naturalistic setting are a useful complement to characterize the drug profile. Objective This multicentre study assessed the effectiveness and tolerability of adjunctive BRV in a large population of patients with focal epilepsy in the context of real-world clinical practice. Methods The BRIVAFIRST (BRIVAracetam add-on First Italian netwoRk STudy) was a retrospective, multicentre study including adult patients prescribed adjunctive BRV. Patients with focal epilepsy and 12-month follow-up were considered. Main outcomes included the rates of seizure-freedom, seizure response (≥ 50% reduction in baseline seizure frequency), and treatment discontinuation. The incidence of adverse events (AEs) was also considered. Analyses by levetiracetam (LEV) status and concomitant use of strong enzyme-inducing antiseizure medications (EiASMs) and sodium channel blockers (SCBs) were performed. Results A total of 1029 patients with a median age of 45 years (33-56) was included. At 12 months, 169 (16.4%) patients were seizure-free and 383 (37.2%) were seizure responders. The rate of seizure freedom was 22.3% in LEV-naive patients, 7.1% in patients with prior LEV use and discontinuation due to insufficient efficacy, and 31.2% in patients with prior LEV use and discontinuation due to AEs (p < 0.001); the corresponding values for ≥ 50% seizure frequency reduction were 47.9%, 29.7%, and 42.8% (p < 0.001). There were no statistically significant differences in seizure freedom and seizure response rates by use of strong EiASMs. The rates of seizure freedom (20.0% vs. 16.6%; p = 0.341) and seizure response (39.7% vs. 26.9%; p = 0.006) were higher in patients receiving SCBs than those not receiving SCBs; 265 (25.8%) patients discontinued BRV. AEs were reported by 30.1% of patients, and were less common in patients treated with BRV and concomitant SCBs than those not treated with SCBs (28.9% vs. 39.8%; p = 0.017). ConclusionThe BRIVAFIRST provided real-world evidence on the effectiveness of BRV in patients with focal epilepsy irrespective of LEV history and concomitant ASMs, and suggested favourable therapeutic combinations.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 81%

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

et al. 2021

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“…The most frequently reported AEs pertaining to changes in behavior were irritability, depression, and anxiety, which were reported by 1% to 3% of the participants. These findings confirmed the overall favorable tolerability of adjunctive BRV and were consistent with the profile reported in randomized and nonrandomized studies 8–13 …”

Section: Discussionsupporting

confidence: 88%

“…Brivaracetam treatment was discontinued by around one‐fifth of the population. Despite differences in study methodology, the overall rate of withdrawal for adjunctive BRV was substantially consistent with those observed in several retrospective noninterventional studies, 9–12 but lower than the proportion reported by Steinhoff et al, probably due to the inclusion of patients with more severe epilepsies 13 . The main reason for drug withdrawal was lack of efficacy, and the number of lifetime ASMs was an independent predictor of retention time.…”

Section: Discussionsupporting

confidence: 79%

“…Furthermore, if the median time to event is 5 months, this means that one‐half of the patients had their seizure frequency reduced by at least 40%. These figures substantially prove the efficacy of BRV to control seizures when added to the pre‐existing therapeutic regimen in everyday clinical practice and expand from a novel perspective the available findings 8–13 …”

Section: Discussionmentioning

confidence: 60%

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Brivaracetam as add‐on treatment in focal epilepsy: A real‐world time‐based analysis

et al. 2020

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The study assessed the clinical response to add‐on brivaracetam (BRV) in real‐world practice by means of time‐to‐baseline seizure count methodology. Patients with focal epilepsy who were prescribed add‐on BRV were identified. Primary endpoint was the time‐to‐baseline seizure count defined as the number of days until each patient experienced the number of focal seizures that occurred in the 90 days before BRV initiation. Subgroup analysis was performed according to levetiracetam (LEV) status (naive vs prior use). Three‐hundred eighty‐seven patients were included. The overall median time‐to‐baseline seizure count was 150 (95% confidence interval [CI] = 130‐175) days. The median time‐to‐baseline seizure count was 198 (lower limit of 95% CI = 168) days for LEV‐naive patients, 126 (95% CI = 105‐150) days for patients with prior LEV use and withdrawal due to insufficient efficacy, and 170 (95% CI = 128‐291) days for patients who discontinued LEV due to adverse events (P = .002). The number of prior antiseizure medications (adjusted hazard ratio [adjHR] = 1.07, 95% CI = 1.02‐1.13, P = .009) and baseline monthly seizure frequency (adjHR = 1.004, 95% CI = 1.001‐1.008, P = .028) were independently associated with the primary endpoint. Add‐on BRV improved seizure control in LEV‐naive and LEV‐prior patients. The time‐to‐baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.

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Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal‐onset seizures: A phase III randomized, double‐blind, placebo‐controlled trial

Inoue,

Tiamkao,

Zhou

et al. 2024

Epilepsia Open

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ObjectiveEvaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal‐onset seizures (FOS).MethodsPhase III, randomized, double‐blind, placebo‐controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16–80 years) with FOS with/without secondary generalization (focal to bilateral tonic–clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8‐week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12‐week treatment period. Efficacy outcomes: percent reduction over placebo in 28‐day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment‐emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs.ResultsIn this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28‐day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p < 0.0001) with BRV 50 mg/day and 200 mg/day, respectively, 50% responder rate was 19.0%, 41.1%, and 49.3% with placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p < 0.0001 for both BRV groups vs. placebo). Median percent reduction in FOS frequency from baseline was 21.3%/38.9%/46.7% in patients on placebo/BRV 50 mg/BRV 200 mg/day, respectively. Overall, 0, 7 (4.6%), and 10 (6.8%) patients were classified as seizure‐free during the treatment period on placebo, BRV 50 mg/day, and BRV 200 mg/day, respectively (p = 0.0146/p = 0.0017 for BRV 50 mg/200 mg/day vs. placebo, respectively). TEAE incidences were similar between patients on placebo (58.4%) and all patients receiving BRV (58.5%); TEAE incidences for BRV 50 mg/day and BRV 200 mg/day were 57.0% and 60.1%, respectively. Overall, 0.7% of patients on placebo and 2.0% of all patients on BRV reported serious TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 1.3% and 2.7%, respectively), 20.1% of patients on placebo and 33.1% of all patients on BRV reported drug‐related TEAEs (incidences for BRV 50 mg/day and BRV 200 mg/day were 26.5% and 39.9%, respectively), and 4.7% of patients on placebo and 3.0% of all patients on BRV discontinued due to TEAEs (discontinuation incidences for BRV 50 mg/day and BRV 200 mg/day were 2.6% and 3.4%, respectively).SignificanceAdjunctive BRV was efficacious and well tolerated in adult Asian patients with FOS. Efficacy and safety profiles were consistent with BRV studies in predominantly non‐Asian populations.Plain Language SummaryBrivaracetam is used to treat partial or focal seizures in people with epilepsy. Most studies with brivaracetam tablets have involved people from non‐Asian racial backgrounds. In this study, 449 Asian adults with epilepsy took part. One third took 50 mg of brivaracetam, one third took 200 mg of brivaracetam, and one third took a placebo each day for 12 weeks. On average, those who took brivaracetam had fewer seizures than those given the placebo. Most of the side effects were mild and the number and type of side effects seen were as expected for this medication.

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Effectiveness and tolerability of adjunctive brivaracetam in patients with focal seizures: Second interim analysis of 6-month data from a prospective observational study in Europe

Cited by 18 publications

References 17 publications

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Adjunctive Brivaracetam in Focal Epilepsy: Real-World Evidence from the BRIVAracetam add-on First Italian netwoRk STudy (BRIVAFIRST)

Brivaracetam as add‐on treatment in focal epilepsy: A real‐world time‐based analysis

Efficacy, safety, and tolerability of adjunctive brivaracetam in adult Asian patients with uncontrolled focal‐onset seizures: A phase III randomized, double‐blind, placebo‐controlled trial

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