Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial

Toledo, Manuel; Brandt, Christian; Quarato, Pier Paolo; Schulz, Anne-Liv; Cleveland, Jody M.; Wagener, Gilbert; Klein, Pavel

doi:10.1016/j.yebeh.2021.107897

Cited by 13 publications

(13 citation statements)

References 22 publications

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“…Brivaracetam was effective and well-tolerated in this drugresistant cohort, with acceptable retention rates over 36 months of treatment. Our responder rate is comparable to previous cohort studies [16][17][18][19][20][21][22][23][24][25]. For instance, a study reported a responder rate of 53.7% at 36 months [25], comparable to our rate of 57%.…”

Section: Discussionsupporting

confidence: 90%

“…Our responder rate is comparable to previous cohort studies [16][17][18][19][20][21][22][23][24][25]. For instance, a study reported a responder rate of 53.7% at 36 months [25], comparable to our rate of 57%. The retention rates in this cohort, of 57% at 36 months, were higher than those observed in our historical cohort of people on perampanel (43%) and lacosamide (35%) [26,27].…”

Section: Discussionsupporting

confidence: 90%

“…We assessed outcomes of BRV treatment for refractory epilepsy at a single tertiary center. A broad range of clinical phenotypes were evaluated, including people with generalized epilepsy, on more concomitant medications and over more extended followup periods, making this cohort more heterogeneous than previous observational studies [16][17][18][19][20][21][22][23][24][25]. Most of the cohort had previously discontinued LEV due to tolerability issues.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center

Green

Hare²,

Kassam³

et al. 2022

Epilepsy & Behavior

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center

Green

Hare²,

Kassam³

et al. 2022

Epilepsy & Behavior

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“…23 Further, well-controlled seizures result in reduced average annual overall health care costs for all types of seizures ($23 238 in 2007 to $13 839 in 2009) and improved quality of life compared with uncontrolled seizures. [24][25][26] This highlights potential annual savings in care of $9399, inflation-adjusted to $11 644 in 2021, that might be realized if an accurate diagnosis leads to a change in treatment that controls seizures. 25 These observations, together with the finding that genetic testing for epilepsy is a cost-effective strategy in patients without an etiology, 27 demonstrate the benefits of standardizing the use of genetic testing for epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

et al. 2022

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ImportanceIt is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes.ObjectiveTo evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes.Design, Setting, and ParticipantsThis was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals.ExposuresGenetic test results.Main Outcomes and MeasuresClinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms.ResultsAmong 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%).Conclusions and RelevanceResults of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes.

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“…There is a suspect that all ASMs, as a class and across all ranges of indications, may be associated with a small increment of suicidal thoughts or behaviour 32 even though a more recent analysis failed to confirm this finding. 33 In the open-label CNB study, 16 [34][35][36][37][38] are still not available. Hence, we do not know how many drug-resistant patients with focal epilepsies that achieved seizure freedom over few months in the randomized, double-blind studies will keep on without seizures over the years.…”

Section: Drug Reaction With Eosinophilia and Systemicmentioning

confidence: 99%

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults

Zaccara¹,

Lattanzi²,

Leo³

et al. 2021

NDT

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Cenobamate (CNB) is the latest antiseizure medication (ASM) authorized for the treatment of focal-onset seizures in adults. Although the precise mechanism of action of CNB is not yet fully understood, this drug inhibits the persistent, rather than transient, voltage-gated sodium channel currents and is a positive allosteric modulator of synaptic and extrasynaptic GABA A receptors, differently from benzodiazepines. CNB has a non-linear pharmacokinetic with a terminal half-life range of about 50/60 hours within the therapeutic dose range, which allows once daily administration. Cenobamate inhibits cytochrome P450 (CYP) 2C19 and induces CYP3A4 and 2B6, and hence can potentially interact with ASMs (eg, phenytoin, carbamazepine and clobazam) and no-ASMs drugs. In two randomized, double-blind, placebo-controlled trials in patients with focal epilepsies, CNB has shown a particularly good efficacy with a rate of seizure freedom of about 20% during the maintenance period in participants treated with the dose of 400 mg/day. The most common treatment-emergent adverse effects include central nervous systemrelated symptoms, like dizziness, diplopia, somnolence, and gait disturbances. Safety issues of particular interest are severe skin reactions (drug reaction with eosinophilia and systemic symptoms) and QT shortening, which contraindicates its use in subjects with familial short QT syndrome or in combination with other QT-shortening drugs. The recommended starting dose is 12.5 mg/day, which can be gradually titrated to the target dose (200 mg/day) and further increased up to 400 mg/ day. There are several aspects of CNB that need to be still addressed, including the long-term efficacy and the efficacy in patients with generalized seizures. Ongoing studies will clarify these issues. The clinical relevance of the peculiar pharmacokinetics and the pattern of drug-drug interactions also require further investigation.

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Long-term safety, efficacy, and quality of life during adjunctive brivaracetam treatment in patients with uncontrolled epilepsy: An open-label follow-up trial

Cited by 13 publications

References 22 publications

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center

Retention of brivaracetam in adults with drug-resistant epilepsy at a single tertiary care center

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

Critical Appraisal of Cenobamate as Adjunctive Treatment of Focal Seizures in Adults

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