THUR 058 Eslicarbazepine acetate as monotherapy in clinical practice

PurposeTo assess eslicarbazepine acetate (ESL) as monotherapy in everyday clinical practice.MethodEuro-Esli was a pooled analysis of 14 European studies. In a subanalysis, data were compared for patients treated initially with ESL monotherapy versus adjunctive therapy, and for patients treated at last visit with ESL monotherapy versus adjunctive therapy.Assessments included responder rate (≥50% seizure frequency reduction), seizure freedom rate (seizure freedom at least since prior visit) and incidence of adverse events (AEs).ResultsESL was used as monotherapy in 88/2045 and 229/1340 patients initially and at last visit, respectively. At 12 months, responder and seizure freedom rates were significantly higher in patients treated initially with ESL monotherapy versus adjunctive therapy (responder: 94.1% versus 74.8%; seizure freedom: 88.2% versus 39.0%), and in patients treated at last visit with ESL monotherapy versus adjunctive therapy (responder: 93.2% versus 70.4%; seizure freedom: 77.4% versus 25.9%). Overall incidence of AEs was similar in patients treated initially with ESL monotherapy and adjunctive therapy (29.4% versus 34.4%), and in patients treated at last visit with ESL monotherapy and adjunctive therapy (27.1% versus 30.8%).ConclusionESL was significantly more effective when used as monotherapy compared with adjunctive therapy; safety/tolerability was generally comparable.Supported by Eisai

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WED 063 Eslicarbazepine acetate switch from carbamazepine or oxcarbazepine

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-abn.27 ◽

2018 ◽

Vol 89 (10) ◽

pp. A7.3-A7

Author(s):

Peltola Jukka ◽

McMurray Rob ◽

Villanueva Vicente

Keyword(s):

Clinical Practice ◽

Adverse Events ◽

Seizure Frequency ◽

Pooled Analysis ◽

Responder Rate ◽

Seizure Freedom ◽

European Studies ◽

Eslicarbazepine Acetate ◽

Adequate Control ◽

Poor Tolerability

PurposeTo investigate eslicarbazapine acetate (ESL) in patients transitioning from carbamazepine or oxcarbazepine in clinical practice.MethodEuro-Esli was a pooled analysis of 14 European studies. Data were analysed for patients transitioning from carbamazepine and oxcarbazepine to ESL due to lack of efficacy or poor tolerability. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment, and at last visit. Safety/tolerability analysis evaluated adverse events (AEs) and ESL discontinuation due to AEs.ResultsEuro-Esli included 2058 patients; 233 (11.3%) transitioned from carbamazepine and 134 (6.5%) transitioned from oxcarbazepine. After 12 months, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n=163) were 70.0% and 30.9%, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n=90) were 57.1% and 25.0%, respectively. Among patients who transitioned from carbamazepine (n=64) and oxcarbazepine (n=61) due to poor tolerability, 26.6% and 39.5% experienced AEs; 8.3% and 6.8% discontinued ESL due to AEs, respectively.ConclusionESL may be a useful option for patients experiencing intolerable AEs or not achieving adequate control with carbamazepine or oxcarbazepine.Supported by Eisai.

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PERMIT study: a global pooled analysis study of the effectiveness and tolerability of perampanel in routine clinical practice

Journal of Neurology ◽

10.1007/s00415-021-10751-y ◽

2021 ◽

Cited By ~ 1

Author(s):

Vicente Villanueva ◽

Wendyl D’Souza ◽

Hiroko Goji ◽

Dong Wook Kim ◽

Claudio Liguori ◽

...

Keyword(s):

Clinical Practice ◽

Status Epilepticus ◽

Pooled Analysis ◽

Routine Clinical Practice ◽

Responder Rate ◽

Seizure Freedom ◽

Everyday Clinical Practice ◽

Analysis Study ◽

Full Analysis ◽

Generalized Epilepsy

AbstractThe PERaMpanel pooled analysIs of effecTiveness and tolerability (PERMIT) study was a pooled analysis of data from 44 real-world studies from 17 countries, in which people with epilepsy (PWE; focal and generalized) were treated with perampanel (PER). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness assessments included 50% responder rate (≥ 50% reduction in seizure frequency from baseline) and seizure freedom rate (no seizures since at least the prior visit); in PWE with status epilepticus, response was defined as seizures under control. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 5193 PWE. Retention, effectiveness and safety/tolerability were assessed in 4721, 4392 and 4617, respectively. Retention on PER treatment at 3, 6, and 12 months was 90.5%, 79.8%, and 64.2%, respectively. Mean retention time on PER treatment was 10.8 months. The 50% responder rate was 58.3% at 12 months and 50.0% at the last visit, and the corresponding seizure freedom rates were 23.2% and 20.5%, respectively; 52.7% of PWE with status epilepticus responded to PER treatment. Overall, 49.9% of PWE reported AEs and the most frequently reported AEs (≥ 5% of PWE) were dizziness/vertigo (15.2%), somnolence (10.6%), irritability (8.4%), and behavioral disorders (5.4%). At 12 months, 17.6% of PWEs had discontinued due to AEs. PERMIT demonstrated that PER is effective and generally well tolerated when used to treat people with focal and/or generalized epilepsy in everyday clinical practice.

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Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Neurology ◽

10.1212/wnl.0000000000010154 ◽

2020 ◽

Vol 95 (9) ◽

pp. e1244-e1256 ◽

Cited By ~ 13

Author(s):

Dileep R. Nair ◽

Kenneth D. Laxer ◽

Peter B. Weber ◽

Anthony M. Murro ◽

Yong D. Park ◽

...

Keyword(s):

Quality Of Life ◽

Seizure Frequency ◽

Focal Epilepsy ◽

Responder Rate ◽

Seizure Freedom ◽

Open Label ◽

Cognitive Domains ◽

Signed Rank

ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04–9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

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Retention Rate and Efficacy of Perampanel with a Slow Titration Schedule in Adults

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2020.174 ◽

2020 ◽

pp. 1-7

Author(s):

Mazen Basheikh ◽

R. Mark Sadler

Keyword(s):

Seizure Frequency ◽

Retention Rate ◽

Responder Rate ◽

Dose Titration ◽

Seizure Freedom ◽

Chart Audit ◽

Generalized Seizures ◽

Included Patient ◽

Generalized Epilepsy

ABSTRACT: Rationale: The manufacturer of perampanel (PER) suggests an initial adult dose of 2–4 mg/day and an upward dose titration of 2 mg at no more frequently than 1- or 2-week intervals when used with enzyme-enhancing antiepileptic drugs (AEDs) or nonenzyme-enhancing AEDs, respectively. The general practice in our clinic is an initial dose of PER 2 mg/day and titrated by 2 mg/4 weeks to an initial target of 6 mg/day. Methods: Retrospective chart audit of patients starting PER in an adult epilepsy clinic between September 2013 and November 2016 with at least one 6-month follow-up visit was reviewed. Data collection included patient demographics, seizure characteristics, past and concurrent therapy, monthly seizure frequency before PER and at 6-month visit, and characteristics of PER discontinuation. Efficacy of treatment was assessed with the Engel classification and 50% responder rate. Results: N = 102 patients; mean age = 40 years and 54% females. Focal onset seizures 85%, generalized 13%, and unknown 2%. Median prior AED exposure = 6 (range 3–20); median concomitant AED use = 2 (range 1–5). Follow-up range was 6–37 months. The median seizure frequency/month prePER treatment was 6 (range 0–30) for focal onset seizures and 1 (range 0–6) for generalized seizures. The retention rate amongst all patients at 6 months was 78.4%. At 6-month follow-up, 36% of all patients achieved Engel class I (seizure freedom) (30.7% of patients with focal onset seizures and 63.6% with generalized epilepsy). The 50% responder rate was 52% and 82% for focal and generalized epilepsy, respectively. Conclusion: PER has a good retention rate when titrated slowly and thus encouraging seizure freedom results in an otherwise medically refractory epilepsy population.

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Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-317168 ◽

2018 ◽

Vol 89 (7) ◽

pp. 741-753 ◽

Cited By ~ 63

Author(s):

Emily Stockings ◽

Dino Zagic ◽

Gabrielle Campbell ◽

Megan Weier ◽

Wayne D Hall ◽

...

Keyword(s):

Adverse Events ◽

Seizure Frequency ◽

Observational Studies ◽

Number Needed To Treat ◽

Seizure Freedom ◽

Low Grade ◽

Serious Adverse Events ◽

Seizure Reduction ◽

Increased Risk ◽

Randomised Controlled

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.PROSPERO registration numberCRD42017055412.

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SAFETY AND EFFICACY OF ESLICARBAZEPINE ACETATE IN ELDERLY PATIENTS

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2015-312379.52 ◽

2015 ◽

Vol 86 (11) ◽

pp. e4.143-e4

Author(s):

R Costa ◽

N Lopes ◽

H Gama ◽

R Sousa ◽

T Nunes ◽

...

Keyword(s):

Elderly Patients ◽

Seizure Frequency ◽

Adjunctive Therapy ◽

Vital Signs ◽

Phase Iii ◽

Controlled Study ◽

Elderly Subjects ◽

Maintenance Period ◽

Eslicarbazepine Acetate ◽

Once Daily

PurposeTo evaluate the safety/tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in elderly patients with partial-onset seizures (POS).MethodPhase III, multicentre, open-label, non-controlled study in patients aged ≥65 years with ≥2 POS during an 8-week baseline and treated with 1–2 antiepileptic drugs. Following baseline, patients entered a 26-week maintenance period. ESL was initiated at 400 mg once-daily and adjusted (400–1200 mg/day) based on individual response. Safety/tolerability evaluations included treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiogram and physical/neurological examinations. Efficacy evaluations included change in standardised seizure frequency (SSF; seizure frequency/4 weeks).ResultsOf the 72 patients included, 47 (65.3%) experienced 152 TEAEs; most commonly, dizziness (12.5%), somnolence (9.7%), fatigue (8.3%), convulsion (8.3%) and hyponatraemia (8.3%). Three patients died of cardiac failure, glioblastoma multiforme and ischaemic stroke (relationship unlikely/not related). Overall, 16 (22.2%) patients discontinued due to TEAEs. Incidence of clinically significant findings was low for vital signs, electrocardiogram and physical/neurological examinations. SSF decreased from 2.9 at baseline to 1.2 during the maintenance period (median relative change: –54.1%).ConclusionOnce-daily ESL (400–1200 mg) as adjunctive therapy in elderly subjects with POS did not raise major safety concerns and was efficacious. Supported by Bial.

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