Safety, tolerability, and seizure control during long‐term treatment with adjunctive brivaracetam for partial‐onset seizures

Toledo, Manuel; Whitesides, John; Schiemann, Jimmy; Johnson, Martin; Eckhardt, Klaus; McDonough, Belinda; Borghs, Simon; Kwan, Patrick

doi:10.1111/epi.13416

Cited by 63 publications

(92 citation statements)

References 35 publications

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“…Data deriving from a pooled analysis76 including Phase IIb,66,67 Phase III68–71 and associated LTFU studies were consistent with those reported earlier. More in detail, 1,848 (84.5%) out of 2,186 patients treated with BRV 50–200 mg/day, experienced at least one TEAE, which was considered to be drug related in 1,184 (54.2%).…”

Section: Brivaracetamsupporting

confidence: 83%

“…At the clinical cutoff date, BRV exposure was up to 96 months for one LTFU trial. As reported in a pooled analysis,76 the overall median baseline-adjusted reduction in POS/28 days was 48.8%, which increased from 43.1% for the 1,834 patients who received BRV during a 1–3-month period, to 77% for the 540 patients receiving BRV for 58–60 months. Similarly, the percentage of patients with a ≥50% response increased over time, from 43.5% for 1–3 months to 71.0% for 58–60 months.…”

Section: Brivaracetammentioning

confidence: 52%

“…Variables influencing HRQoL are TEAE rate due to anti-epileptic therapy, depression, anxiety, perceived stigma of epilepsy and consequent lack of independence. In this regard, HRQoL was assessed in a large pooled analysis76 including patients from Phase IIb, III and LTFU studies, using the Quality of Life in Epilepsy Inventory-31 (QOLIE-31P), a patient-reported instrument evaluating seven subscales. In the efficacy population (BRV modal doses 50–200 mg/day, n=1,836), improvements in HRQoL were reported in 45% of patients from month 2, with a tendency to increase until month 42 for patients who entered LTFU studies.…”

Section: Patient-focused Perspectivesmentioning

confidence: 99%

“… Note: Data from Toledo et al76 Abbreviations: BRV, brivaracetam; LTFUs, long-term follow-up studies; SAE, serious adverse event; SUDEP, sudden unexpected death in epilepsy; TEAE, treatment-emergent adverse event.…”

Section: Tablementioning

confidence: 99%

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New developments in the management of partial-onset epilepsy: role of brivaracetam

Coppola¹,

Iapadre²,

Operto³

et al. 2017

DDDT

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Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children. Among the newest anticonvulsant drugs, brivaracetam, a high-affinity synaptic vesicle protein 2A ligand, reported to be 10- to 30-fold more potent than levetiracetam, is highly effective in a broad range of experimental models of focal and generalized seizures. Unlike levetiracetam, brivaracetam does not inhibit high-voltage Ca2+ channels and AMPA receptors and appears to inhibit neuronal voltage-gated sodium channels playing a role as a partial antagonist. Brivaracetam has a linear pharmacokinetic profile, is extensively metabolized and is excreted by urine (only 8%–11% unchanged). It does not seem to influence the pharmacokinetics of other antiepileptic drugs. It was approved in the European Union in January 2016 and in the US in February 2016 as an adjunctive therapy for the treatment of POS in patients older than 16 years of age. To date, its clinical efficacy as adjunctive antiepileptic treatment in adults with refractory POS at doses between 50 and 200 mg daily has been extensively assessed in two Phase IIb and four Phase III randomized controlled studies. Long-term extension studies show sustained efficacy of brivaracetam. Overall, the drug is generally well tolerated with only mild-to-moderate side effects. This is true also by intravenous route. Brivaracetam has not yet been evaluated as monotherapy or in comparison with other new anticonvulsant drugs.

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Section: Brivaracetamsupporting

confidence: 83%

Section: Brivaracetammentioning

confidence: 52%

Section: Patient-focused Perspectivesmentioning

confidence: 99%

Section: Tablementioning

confidence: 99%

See 2 more Smart Citations

New developments in the management of partial-onset epilepsy: role of brivaracetam

Coppola¹,

Iapadre²,

Operto³

et al. 2017

DDDT

View full text Add to dashboard Cite

show abstract

“…BRV had a placebo‐adjusted nonpsychotic behavior rate of 2.6% compared to 6.1% for LEV, which resulted in an odds ratio of 0.68 (95%CI 0.32‐1.45) . The discontinuation rate of BRV due to any adverse effects was 12.1% (risk ratio 1.58; 95%CI 1.04‐2.40, P = .034) …”

Section: Adverse Drug Reactions and Drug‐drug Interactionsmentioning

confidence: 99%

Brivaracetam: An Adjunctive Treatment for Partial-Onset Seizures

Kappes

Hayes

Strain

et al. 2017

The Journal of Clinical Pharmacology

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Brivaracetam is an analogue of levetiracetam that is Food and Drug Administration-approved for adjunctive treatment of partial-onset seizures in patients 16 years and older. In placebo-controlled trials adjunct brivaracetam demonstrated efficacy in reducing the frequency of seizures. The most commonly reported adverse effects are somnolence, dizziness, and fatigue. Clinical trials have evaluated brivaracetam for safety and efficacy in adjunctive treatment of partial-onset seizures in patients 16 years and older for up to 16 weeks. Brivaracetam's mechanism is similar to that of levetiracetam but with greater receptor binding affinity on synaptic vesicle protein 2A and inhibitory effects on sodium channels. Clinically significant differences between these agents are undetermined. Brivaracetam is available as oral tablets, oral solution, and intravenous solution. The Food and Drug Administration-approved dose is 50 mg twice daily, and titration is not required. Brivaracetam does not need dose adjustment for renal impairment and has minimal drug-drug interactions. Current limitations of brivaracetam include lack of head-to-head trials, limited long-term safety and efficacy data, and cost. Overall, brivaracetam is a viable adjunct therapeutic option for refractory partial-onset seizures in those who have failed conventional therapies.

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Brivaracetam substituting other antiepileptic treatments: Results of a retrospective study in German epilepsy centers

et al. 2020

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Objective To evaluate the success of initiation of adjunctive brivaracetam in patients who required a change in antiepileptic drug (AED) regimen and substituted at least one AED with brivaracetam. Methods In this retrospective noninterventional study conducted in specialized epilepsy centers across Germany, patients initiated adjunctive brivaracetam between February 15, 2016, and August 31, 2016, as part of an intended change in AED regimen. The primary effectiveness variable was the proportion of patients who continued on brivaracetam after 3 months, and withdrew at least one AED either before or within 6 months after brivaracetam initiation. Results Five hundred and six patients had at least one brivaracetam dose and were included in the safety set (SS). Four hundred and seventy patients started to reduce the dose of one AED before/after brivaracetam initiation, had at least one concomitant AED at brivaracetam initiation, and were included in the full analysis set (FAS) for effectiveness analyses. At baseline, patients had a median of seven lifetime AEDs and a median of 3.8 seizures/28 days. In the SS, 85.2% of patients withdrew one AED before/after initiation of brivaracetam, most commonly levetiracetam (49.4%). 46.2% of patients substituted another AED with brivaracetam within 24 hours (fast withdrawal). The proportions of patients (FAS) who continued on brivaracetam after 3 and 6 months and withdrew one AED were 75.5% and 46.6%, respectively. After 6 months, 32.1% of patients were 50% responders; 13.0% were seizure‐free. In the SS, 34.6% of patients reported treatment‐emergent adverse events (TEAEs); 21.9% had TEAEs that were assessed by the treating physician as drug‐related. Incidences of behavioral AEs before (3‐month baseline) and after brivaracetam initiation in patients who withdrew levetiracetam were 19.2% and 8.0%, respectively (5.0% and 7.7% in patients who withdrew other AEDs). Significance Brivaracetam was effective and well‐tolerated in patients who required a change in AED drug regimen and initiated adjunctive brivaracetam in German clinical practice.

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Safety, tolerability, and seizure control during long‐term treatment with adjunctive brivaracetam for partial‐onset seizures

Cited by 63 publications

References 35 publications

New developments in the management of partial-onset epilepsy: role of brivaracetam

New developments in the management of partial-onset epilepsy: role of brivaracetam

Brivaracetam: An Adjunctive Treatment for Partial-Onset Seizures

Brivaracetam substituting other antiepileptic treatments: Results of a retrospective study in German epilepsy centers

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