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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5203_Библиотеки_им_академика_М_И_Перельмана.pdf
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seizures, 16% with generalized seizures and 3% with unclassied seizures. Nine
patients received BRV monotherapy. At the rst follow-up, 56 patients (36%)
showed seizure cessation, 24 patients (15%) had no signicant change in seizure
frequency, 6 patients (4%) had an increase in seizure frequency, and 9% had a
decrease of less than 50% in seizure frequency. Adverse events occurred in 26
patients (17%) but were not life-threatening. The authors concluded that BRV is an
effective, easy to use and safe ASM.
Stephen etal. [739] described the practice of BRV treatment in epilepsy clinics.
They initiated BRV after 12weeks of stable ASM treatment in patients older than
16 years with refractory epilepsy, at a target dose of 200mg/day, and repeated
examinations at 12- to 16-week intervals. A total of 108 patients were enrolled in
the study, including 38 men and 70 women. Eighty-eight patients presented with
focal epilepsy, 20 with hereditary generalized epilepsy, and 53 patients had previously used LEV and discontinued it due to ineffectiveness or side effects. Seizure
reduction of more than 50% was observed in 71 patients (65.7%), 23 of whom
(21.3%) remained seizure-free for more than 6months. Four patients with juvenile
myoclonic epilepsy had complete control of generalized tonic–clonic seizures,
absence seizures and myoclonic seizures. The authors suggest that BRV is effective
in various seizure types with a wide range of doses. BRV is also effective for patients
who failed to respond to LEV treatment.
Nearly half of patients with epilepsy (PWE) have seizure clusters (SCs) and are
at risk of subsequent hospitalization. Orlandi N etal. [740] evaluated the treatment
of SCs (≥2seizures/24h) with intravenous BRV.Of 97 patients (mean age 62years)
enrolled, 74 (76%) had a history of epilepsy (with drug-resistant seizures in 49% of
cases); BRV was administered as rst-line therapy in 16% of patients, whereas it
was used as a rst-line/second-line agent after benzodiazepine failure in 49% and
35% of patients, respectively. It was found that 58% of patients were seizure-free at
24h after BRV administration, and 75 of 97 patients (77%) were not using other
drugs. In patients without a history of epilepsy and who used BRV as a second or
third-line agent, a higher likelihood of seizure recurrence and/or evolution to status
epilepticus was observed. No serious treatment-emergent adverse events were
observed. The authors concluded that intravenous BRV administration was welltolerated in the treatment of SCs and could be considered as a treatment option,
especially in the case of an in-hospital onset.
Long-Term Efcacy andSafety ofBRV
To evaluate the long-term efcacy, retention, and tolerability of BRV add-on therapy, Strzelczyk etal. [741] conducted a multicenter, retrospective cohort study of
patients treated with BRV between February and November 2016. They analyzed
data from a 5-year observation period of 262 patients (mean age, 40years; range,
5–81years; 129 men), 227 of whom (87%) were diagnosed with focal epilepsy, 19
(7%) with hereditary generalized epilepsy, and 16 (6%) with other or unclassied
epilepsy syndromes. Only 26 patients (10%) had never received LEV and 133
(50.8%) had switched from LEV to BRV.The total duration of BRV treatment was
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6829 person-months (569 years). Seizures were reduced by more than 50% in
33.1% (79/239) patients, and 10.9% of them were seizure-free. Twenty-three
patients were lost to follow-up. The retention rate was 61.1% at 12months and
50.8% over the course of the study. At the last follow-up, 133 patients had received
BRV at a mean dose of 222±104mg. Of these patients, 52 (39.1%) exceeded the
upper limit of the recommended dose (200mg). The authors concluded that although
90% of the patients had previously used LEV, there was still a 33% efcacy at
12months, with an overall retention rate of >50%. They concluded that BRV had a
good long-term efcacy and was well-tolerated for those types of epilepsy.
To evaluate the long-term efcacy and safety of BRV in patients with epilepsy,
Manuel Toledo etal. [742] conducted a multicenter clinical trial with the use of variable doses of BRV for the treatment of patients with focal or generalized epilepsy.
Of 766 patients treated with BRV (753 with focal seizures and 13 with generalized
seizures), 51.7% had a >50% reduction in seizure frequency; 26% of patients were
seizure-free at 6months and 17.9% were seizure-free at 12months, with a median
of 52.0% reduction in seizure frequency. 42.4% of patients had a clinically meaningful improvement in the weighted Quality of Life Epilepsy Questionnaire 31 total
score at 12months and 46.8% at 24months. The Kaplan–Meier calculated retention
rate was 71.9% at 12months and 53.7% at 36months; 257 patients (33.6%) had
drug-related adverse events, 49 (6.4%) had somnolence, and 41 (5.4%) had dizziness. Ninety-one patients (11.9%) discontinued BRV due to adverse events. The
authors concluded that BRV was safe and generally effective. Simona Lattanzi etal.
[743] conducted a network meta-analysis (NMA) to evaluate and compare the efcacy and safety of BRV, cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM), and perampanel (PER) for adult focal seizures. They systematic
searched MEDLINE, the Cochrane Central Register of Controlled Trials
(CENTRAL), and the US National Institutes of Health Clinical Trials Registry
(http://www.clinicaltrials.gov). These randomized, double-blinded, controlled,
parallel- group studies compared oral administration of the above ASMs with other
comparators over a maintenance period of at least 12weeks. The efcacy outcome
was the proportion of patients with ≥50% and 100% reduction in baseline seizure
frequency during the maintenance period, and the tolerability outcome was the proportion of participants who experienced at least one treatment-emergent adverse
event (TEAE) and who experienced at least one TEAE leading to discontinuation of
treatment. A total of 16 trials were included, including an overall enrollment of
4507 patients randomized to ASM treatment (BRV=803, CNB=221, ESL=990,
LCM=1104, PER=1389) and 2246 patients given placebo. Finally, cenobamate
scored best for efcacy, and BRV and LCM were better-tolerated than the
other drugs.
Efcacy ofBRV onEpileptic Seizures inChildren
Ferretjans etal. [744] studied the efcacy and safety of BRV in 66 children with
epilepsy. The mean age of the patients was 8.8years (range 1–16years). 93.4% of
the patients had drug-resistant epilepsy, and 27 of them had epileptic
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W. Jing et al.
encephalopathy. The median dose of BRV used was 4.3mg/kg/day. The results
showed that 30.3% of the patients had a >50% reduction in seizure frequency, and
9% of the patients became seizure-free. When LEV treatment was ineffective, LEV
was switched to BRV, and the efcacy was better in patients receiving higher doses.
The authors speculated that BRV was effective for children with refractory epilepsy.
Alberto Verrotti etal. [745] noted that most studies on efcacy and tolerability
have been conducted in adult cohorts, while few studies have been conducted in
children, especially in those with generalized epilepsy and epilepsy syndromes;
BRV is an ASM suitable for focal epilepsy in children. To evaluate the efcacy of
BRV in children with epilepsy and epilepsy syndromes, the authors conducted a
comprehensive review of the relevant literature and concluded that BRV was effective and safe in children with epilepsy. Among the children, there was more evidence of its effectiveness in children aged 4–16years with focal seizures. Benets
have also been reported in patients with epileptic encephalopathy, such as Jeavons
epilepsy, Dravet syndrome, Lennox–Gastaut syndrome, and juvenile myoclonic
epilepsy. Song T etal. [746] searched four databases including PubMed, Embase,
Web of Science and Cochrane Library. A total of 1884 articles were obtained on the
use of BRV monotherapy or adjuvant therapy in the included children (age
≤18years), and 9 articles were ultimately included, including 503 children with
epilepsy. The retention rate of BRV treatment was 78%, the response rate (≥50%
reduction in seizure frequency) was 35%, the seizure freedom rate was 18%, and the
incidence of all treatment-related adverse events (TEAEs) was 39%. The most common TEAEs were somnolence (9%) and mental or behavioral disorders (12%).
These results suggested that BRV seems to be safe and effective in the treatment of
epilepsy in children.
BRV Treatment ofRefractory Epilepsy
Ersilia Savastano etal. [747] evaluated the clinical and electroencephalographic
effects of BRV (50–200mg) in 76 patients aged ≥16years with drug-resistant focal
epilepsy. Seizure frequency of the 54 patients remaining in the study at 6months
was reduced >50% in 29.6% of cases (responders), <50% in 31.5% (nonresponders
1), and it remained unchanged in 38.8% (nonresponders 2). Twenty-nine percent of
patients discontinued BRV early because of a lack of efcacy or minor adverse
effects (AEs) like irritability, asthenia or headache. EEG quantitative analysis
showed a signicant decrease in α absolute power at 6months. The θ band power of
patients with no response was signicantly higher than that of patients who
responded. The δ+θ/α+β index of patients with side effects was higher than that
of patients who did not have side effects. The authors speculated that BRV has a
good efcacy, safety and tolerability, with a good behavioral prole. The reduction
of α band power was related to its sedative effect, the increase of θ band power can
be considered as a predictor of inadequate response to treatment, and the increase of
δ+θ/α+β index may be a predictor of adverse events.
Svendsen T etal. [748] retrospectively collected data on patients older than 18years
of age with refractory epilepsy and started to receive BRV treatment from 2016 to
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253
2019, and followed the clinical and laboratory data of the patients for more than 1year
or when the patient stopped BRV treatment. The results suggested that BRV treatment
had a response rate of 48% in adults with intractable epilepsy after 1year, and BRV
was generally well tolerated, but psychiatric adverse effects such as increased irritability, anxiety, and depressive symptoms occurred in one-third of patients.
Anniko Snoeren etal. [749] explored whether BRV could signicantly improve
the treatment effect and reduce treatment-induced adverse events (TEAEs) in
patients with refractory epilepsy who had failed to respond to previous LEV treatment. The mean time since the rst seizure in the enrolled patients was 25.4years.
Among the 379 patients, 82.8% were diagnosed with focal epilepsy and 9.8% with
generalized epilepsy. The median duration of treatment was 39months for LEV and
20months for BRV.The mean maximum dose was 1749.9mg/day for LEV and
144.2mg/day for BRV.Two hundred and eight patients (54.9%) directly switched
from LEV to BRV.There was a certain time interval between LEV withdrawal and
BRV initiation in 171 (45.1%) patients. The average interval was 77.7months. Of
the patients who discontinued BRV, 30 (24.8%) switched back to
LEV. Discontinuation of initial LEV therapy was due to TEAEs in 63.6% of
patients, including behavioral TEAEs in 55.1% of patients. 24.0% of the patients
discontinued BRV due to inadequate efcacy, 47.1% due to TEAEs, and 22.3% due
to both inadequate efcacy and TEAEs. Regarding efcacy, the analysis showed no
signicant difference between positive response rates to LEV or BRV. 78.0% of the
patients who responded positively to LEV treatment also responded positively to
BRV treatment. 46.2% of the nonresponders to LEV had a positive response to
BRV.Compared with those treated with LEV, patients treated with BRV reported
signicantly fewer TEAEs. The difference in TEAEs was greatest in the “behavior”
category. Newly discovered behavioral TEAEs after switching from LEV to BRV
accounted for 7.1%. The authors suggested that BRV was better tolerated than LEV,
especially for behavioral TEAE. Efcacy analysis showed that when patients
responded positively to LEV, they were likely to respond positively to BRV.The
lack of response to LEV did not affect the positive response to BRV.In summary,
BRV appeared to be an alternative treatment option for patients previously treated
with LEV.
BRV onEpilepsy withOther Diseases
Patients with intellectual disabilities are often excluded from clinical trials, and little is known about the best way to treat epilepsy in patients with intellectual disabilities. BRV is a new type of ASM and is often used as an adjuvant therapy for focal
epilepsy patients with or without secondary generalized seizures. To understand the
effect and safety of BRV on seizures in epilepsy patients with intellectual impairment, Ruby M E Gillis etal. [750] investigated the efcacy and tolerability of BRV
in patients with epilepsy and intellectual impairment who had or had not previously
received LEV treatment. The study enrolled 116 patients (mean age 34.9years;
44% women). All patients completed 3months of follow-up, 76 patients completed
6months of follow-up and 39 patients completed 1year of follow-up. The median
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initial dose of BRV was 50mg/day, and an average of 2.6 other ASMs were simultaneously used. It was found that more than 50% of the patients had a reduction in
seizure frequency. The retention rates after 3, 6, and 12months were 84.4%, 75.5%,
and 58.1%, respectively. There were no signicant differences in seizure reduction
and side effects between patients with and without prior LEV treatment. The authors
concluded that BRV was effective and well-tolerated in epilepsy patients with intellectual impairment, and in patients who had failed previous treatment with LEV.
Approximately 13% of cancer patients have seizures. Patients who cannot normally use ASMs are treated by subcutaneous injection of midazolam, but this may
cause sedation. BRV is an effective ASM for cancer patients with partial and refractory epilepsy with or without generalized seizures. It has fewer behavioral or psychiatric side effects than LEV, has a very low incidence of drug interactions, can be
administered by injection, and thus may be used in patients with seizures that occur
secondary to cancer. Bond etal. [751] described three cancer patients in whom subcutaneous BRV injection successfully controlled seizures during inpatient palliative
care. The dose of BRV was switched from oral to subcutaneous injection at a ratio
of 1:1, and no adverse effects were observed.
Poststroke epilepsy (PSE) is one of the most common causes of acquired epilepsy, accounting for approximately 10–15% of all newly diagnosed epilepsy.
Simona Lattanzi etal. [752] evaluated the efcacy and tolerability of adjuvant BRV
in the treatment of PSE patients for 12months. At 12months, 32 patients (42.7%)
had at least a 50% reduction in baseline seizure frequency, and 26 of 75 patients
(34.7%) were seizure-free. During the 1-year study period, ten patients (13.3%)
discontinued BRV due to poor efcacy in six patients (8.0%) and four patients
(5.3%) discontinued BRV due to poor tolerability. Adverse events were reported in
13 patients (20.3%), 84.6% of which were mild and 15.4% were moderate. It can be
seen that in clinical practice, adjuvant BRV therapy is signicantly effective and
generally well-tolerated when used in PSE patients, and BRV can be a suitable treatment option for PSE patients.
Evidence-Based Medical Research
Madhuri Khilari etal. [753] speculated that the efcacy of BRV as a new type of
ASM in early addition to treatment was not clear. To evaluate the efcacy and safety
of BRV as an early addition treatment for refractory focal epilepsy, six randomized,
parallel, and controlled trials were selected from Medline and Cochrane Central
databases for meta-analysis. Among 1938 patients with focal epilepsy who received
BRV as early add-on therapy, the hazard ratio for a 50% reduction in seizure numbers was 1.88, and the overall hazard ratio was 5.82. The authors suggest that their
study provides some evidence for the clinical efcacy of BRV as an adjuvant in the
early treatment of focal epilepsy, and that its efcacy in several other indications
needs further clinical trials and evaluation. Eleonora Tulli etal. [754] retrospectively analyzed randomized controlled trials, retrospective studies and prospective
studies of BRV in the treatment of partial epilepsy published before December 2020
from the MEDLINE, EMBASE and Clinical Trial databases. It was considered that
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255
analysis of literature data had demonstrated the safety and efcacy of BRV in pediatric epilepsy patients, with more evidence in children who developed focal epilepsy between the ages of 4–16years. BRV may also be effective in some patients
with epileptic encephalopathy, but comparative efcacy studies with other ASMs
are needed to better determine the role and potential of this ASM.
Rebecca Bresnahan etal. [755] published a Cochrane review in 2022 to evaluate
the efcacy and tolerability of BRV as an additional treatment for drug-resistant
epilepsy patients and included six studies. They found that BRV, when used as an
add-on therapy in patients with drug-resistant epilepsy, may be effective in reducing
the frequency of seizures and may help patients achieve seizure freedom. However,
BRV add-on therapy, compared with placebo, may be associated with treatment
discontinuation due to adverse events. Only one eligible study included subjects
with generalized epilepsy, none of the included studies involved subjects under
16years of age, and all were short-term studies. Therefore, the results of this evaluation were mainly applicable to adult patients with drug-resistant focal epilepsy.
Efcacy-Based onReal-World Studies
Simona Lattanziet al. [756] used a time-baseline counting method to evaluate the
clinical efcacy of BRV addition in practical applications. A total of 387 patients
were included in the study. The overall median time-to-baseline seizure count was
150days. The median time-to-baseline seizure count was 198days for LEV-naïve
patients, 126days for patients with prior LEV use and withdrawal due to insufcient efcacy, and 170 days for patients who discontinued LEV due to adverse
events (P=0.002). The number of prior ASMs used and baseline monthly seizure
frequency were independently associated with the primary endpoint. Add-on BRV
treatment improved seizure control in LEV-naïve and LEV-prior use patients. The
time-to-baseline seizure count represents an informative endpoint alongside traditional study outcomes and designs.
Due to the aging population, the management of epilepsy in the elderly has
become a daily issue. Simona Lattanzi etal. [757] evaluated the effectiveness and
tolerability of adjuvant BRV treatment for 12 months in middle-aged and elderly
epilepsy patients (≥65years old) in the real world. A total of 1029 patients with
focal epilepsy were included in this multicenter retrospective study. Efcacy outcomes included the rate of seizure remission (≥50% reduction in baseline seizure
frequency), freedom from seizures, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse
events and the incidence of adverse events. Date of patients aged ≥65years (elderly
group, 111 patients, 10.8%) was compared with that of patients aged <65years
(younger group). The results showed that at 3months, the median daily BRV dose
was 100 (100–175) mg in the elderly group and 100 (100–200) mg in the young
group. 150 (100–200) mg was the median dose in both groups at 6 months or
12months. At 12months, 49 elderly patients (44.1%) and 334 younger patients
(36.4%) had at least a 50% reduction in baseline seizure frequency, and seizure-free
rates were 35/111 (31.5%) and 134/918 (14.6%), respectively. During the one-year
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W. Jing et al.
study period, 20 patients (18.0%) in the older group and 245 patients (26.7%) in the
younger group discontinued BRV.Discontinuation of treatment because of inadequate efcacy was less common in older patients than in younger patients. Adverse
events were reported by 24.2% of the older patients and 30.8% of the younger
patients. The most common adverse events were somnolence, nervousness and/or
agitation, vertigo, and fatigue in both study groups. The authors concluded that
BRV was an effective, well-tolerated adjuvant drug, and no new or unexpected
safety issues have emerged in clinical use. In the elderly population, brivaracetam is
a suitable treatment option.
BRV forStatus Epilepticus
Martellino C etal. [758] evaluated the efcacy and tolerability of intravenous BRV
as a second-line treatment for status epilepticus (SE). Twenty-one patients (median
age 68±17.28years) were treated with BRV (50–200mg) as second-line add-on
therapy for SE.Nearly a quarter of the patients had generalized seizures, while the
vast majority (76.2%) presented with focal seizures. In 52.4% of the patients, the
underlying cause was cerebrovascular disease. Fourteen patients (66.7%) showed a
good early response to the drug within 6h after the onset of seizures, and eight
patients (38%) and 11 patients (52.4%) were seizure-free at 12 and 24h, respectively. This study suggested that BRV can be used as an advantageous weapon for
early addition treatment of SE.
Orlandi etal. [759] studied the efcacy and adverse events of intravenous BRV
for SE in 24 Italian hospitals. Fifty-six patients were enrolled; their mean age was
62years, 57% were men, and 21 (38%) had previous epilepsy. Regarding SE etiology classication, 46% of the patients were acute symptomatic, 18% were remote,
and 16% were progressive symptomatic. About 80% of the patients had motor seizures. After benzodiazepine treatment failure, BRV was used as a rst choice in
21% of patients and as a second or third (or more) choice in 38% of each. The
median loading dose of BRV therapy was 100mg (range 50–300mg). Responses
were found in 32 patients (57%). An early response was documented in 22 patients
(39% of the whole sample). The use of the BRV within 6h from SE onset was independently associated with an early SE resolution. No severe treatment-emergent
adverse events were observed. The authors concluded that BRV was safe and effective in the treatment of SE, especially in the early stage of SE.
Alfredo De Liso etal. [760] reported a rare case of successful control of nonconvulsive status epilepticus by enteral administration of BRV. The patient was an
82-year-old woman who presented with elevated blood pressure, severe headache,
and two focal motor seizures 4days after right carotid endarterectomy. A CT scan
showed right hemisphere edema with a 5 mm midline shift. EEG monitoring
revealed persistent epileptiform discharges in the right hemisphere, consistent with
the diagnosis of SE.She was treated with intravenous phenytoin (PHT), lacosamide
(LCM), and LEV, but these were not effective. After an experimental treatment with
200mg BRV administered through a nasogastric tube, her seizures improved signicantly. The authors suggested that BRV could improve clinical seizures in
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patients with refractory status epilepticus. Enteral administration through a nasogastric tube should be considered.
Methodological Studies onClinical Use ofBRV
Junichi Yamamoto et al. [761] conducted intravenous injection of 100mg BRV,
15min of infusion, and oral administration in 24 healthy subjects, and found that
there was no need to adjust the dose when changing from oral dose to intravenous
dose because the response of epilepsy patients to BRV was related to the exposure
dose (AUC). Beatriz Chavarria etal. [762] observed electrophysiological changes
10min after intravenous injection of BRV (100mg) correlated with its effects on
brain dynamics after blood–brain barrier diffusion. They suggest that rapid BRV IV
infusion has a favorable safety prole and is effective in controlling seizure series in
the short term.
Mark Kristof Farkaset al. [763] evaluated the pharmacokinetics, safety, and tolerability of BRV in children with epilepsy between 15min intravenous infusion and
a single injection (≤2min injection). Children received up to 5mg/kg/day BRV (no
more than 200mg/day). No new safety concerns were identied in children 1month
to 16years of age. Plasma concentrations were within the expected range, and no
unanticipated pharmacokinetic differences were observed between patients who
received either a 15-min infusion or a one-time injection.
Kiwon Lee etal. [764] also evaluated the clinical pharmacology, safety, tolerability, efcacy, and effectiveness of the use of intravenous BRV in the treatment of
acute seizures in critically ill patients. PubMed was searched from its inception to
April 13, 2021, and a total of 12 studies were included. The results showed that
intravenous BRV was generally well-tolerated in patients with acute seizures in the
hospital setting, with a low incidence of individual TEAEs classied as behavioral
disorders. Intravenous BRV administration demonstrated efcacy and effectiveness,
with a rapid onset of action, clinical and electrophysiological improvement of seizures observed within minutes, and general tolerability in patients with status epilepticus. The authors suggested that intravenous BRV showed efcacy and was
generally well tolerated in the treatment of acute epilepsy in hospitalized patients
requiring rapid dosing, which represents a possible use of BRV in an intensive care
setting.
To understand the effects of different doses of BRV on seizures, Ben-Mnachem
etal. [765] analyzed the long-term safety and tolerance of individualized doses of
BRV in patients with focal epilepsy or generalized epilepsy or Unverricht-Lundborg
disease. Overall, 72.6% patients discontinued the trial, mainly due to lack of efcacy (41.5%), adverse events (11.7%), and patient choice (11.5%). Overall, 720/853
(84.4%) patients reported TEAEs, 451 (52.9%) had a drug-related TEAE, and 95
(11.1%) discontinued BRV due to a TEAE.In the ULD subgroup, 87/94 (92.6%)
patients reported TEAEs, 60 (63.8%) had a drug-related TEAE, and 16 (17.0%)
discontinued due to a TEAE.
The most commonly used BRV dose was 150mg/day (48.7%). In the UnverrichtLundborg subgroup, the most common BRV dose was 100 mg/day (46.8%) and
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39.4% of patients took BRV for 96months. Focal seizure frequency compared to
baseline was 43.1%, the 50% responder rate was 43.6%, and 6-and 12-month seizure freedom rates were 22.2% and 15.8%, respectively. The authors concluded
that, overall, BRV was well-tolerated as a long-term adjuvant therapy in patients
with focal epilepsy, generalized epilepsy, or Unverricht-Lundborg syndrome, with
continuous improvement in focal seizure frequency maintained over time.
To understand the relationship between different doses of BRV and the number
of ASMs taken before medication and clinical efcacy and safety, Sang-Kun Lee
etal. [432] randomly assigned focal epilepsy patients taking 1–2 kinds of ASMs to
take 50, 100, or 200mg/day BRV or a placebo, and evaluated the results after summarizing the data. The results showed that in the subgroups of ≥5 ASMs (50, 100,
and 200mg/day BRV), the percentage of decrease in focal seizure frequency after
28days of adjustment compared to placebo was 13.0% in the 50mg/day group,
18.1% in the 100mg/day group, 19.8% in the 200mg/day group, and 17.0% in all
BRV treatment groups. The 50% reduction rates of epileptic seizures in the 50, 100,
200, and 50–200 mg/day BRV groups were 26.9%, 29.9%, 30.0%, and 29.7%,
respectively (placebo: 13.2%); For the 100, 200, and 50–200mg/day BRV groups,
there was a statistically signicant difference in the ratio compared to the placebo
group. In the immediate administration of 0–4 ASMs subgroups (50, 100, 200mg/
day BRV), all BRV dose groups showed statistical differences in the following three
aspects: (1) Compared with the placebo group, the frequency of focal epileptic seizures adjusted for 28days decreased to 21.4–28.7%; (2) Compared with the placebo
group, there was a signicant difference in the median percentage reduction of focal
seizure frequency from baseline after 28days of adjustment, with the BRV groups
accounting for 35.5–45.9% and the placebo group accounting for 21.3%; (3)
Compared to the placebo group, the advantage of a 50% reduction in seizures was
more favorable for the BRV groups. Among patients receiving BRV treatment, the
incidence of adverse events was 73.8%, with 10.5% discontinuing medication due
to adverse events. Adverse events were more common in subgroups using ≥5 ASMs
than in subgroups using 0–4 ASMs. Serious adverse reactions were rare in both
subgroups (3.1% for past ≥5 ASMs; 2.9% for past 0–4 ASMs), indicating that the
addition of BRV in the treatment of focal epilepsy in adults was effective and welltolerated, regardless of the number and type of ASMs previously taken.
Side Effects ofBRV
About 24.2% of 66 patients treated by Ferretjans etal. [744] experienced side effects
of varying degrees, the most common of which were irritability and lethargy. In a
study of 262 patients using BRV long-term, Strzelczyk etal. [741] found that psychological and behavioral abnormalities occurred in 1/10 patients. Ruby M E Gillis
etal. [750] studied the safety of BRV in 116 epilepsy patients with or without previous LEV treatment and intellectual disability, and found that the most-reported side
effects were drowsiness, dizziness, and aggression. In a study by Linda Stephen
[739], among 108 patients taking BRV, 37 (34.3%) discontinued brivaracetam, 23
of which were due to side effects, four due to ineffectiveness, and 10 due to both.
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Sedation was the most common side effect leading to the discontinuation of brivaracetam, followed by mental and behavioral abnormalities. Kuan-Ying Li etal. [766]
conducted a literature review using Cochrane Library, PubMed/MEDLINE, and
Embase, and the analysis showed that BRV had limited effects on cognition and
behavior. For patients who could not tolerate LEV and had side effects of LEVrelated behavioral disorders, A switch to BRV may be benecial.
Cost-Utility ofBRV Addition inPatients withEpilepsy
To evaluate the cost-utility of BRV compared with the third generation ASMs,
Barrachina-Martinez etal. [767] used the Markov model to simulate the cost-utility
of BRV in 2years of treatment, and found that the incremental cost-utility ratio of
BRV was better than that of LCM and zonisamide. Treatment with BRV was considered to be highly cost-effective. However, there were different views. Mehta D
etal. [768] compared all-cause and epilepsy-specic pharmacy costs and total costs
associated with initiation of eslicarbazepine acetate (ESL) or brivaracetam (BRV)
among patients with focal seizures in long-term care (LTC) in the United States.
The results suggested that ESL initiation, compared with BRV, was associated with
33.3% lower all-cause pharmacy costs, 34.4% lower epilepsy-specic pharmacy
costs, 21.3% lower all-cause total costs and 30.9% lower epilepsy-specic total costs.
2.1.3.4 Runamide (RFN)
Drug Characteristics
[Chemical name] 1-(2,6-Diuorobenzyl)-1H-1,2,3-triazole-4-formamide
[Structural formula]
[Molecular formula] C10H8F2N4O
[Molecular weight] 238.193
[Indications] This novel antiepileptic compound can be used as an adjunct therapy
for Lennox–Gastaut syndrome.
[Specications] 100mg