Dataset Information

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

ABSTRACT:

Introduction

Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design.

Objective

The aim of this study was to systematically review the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

Methods

Electronic and clinical trials databases were searched for RCTs of perampanel published up to March 2013. Outcomes of interest were 50 % responder rates, seizure freedom, treatment-emergent adverse events (TEAEs) and incidence of withdrawal. Meta-analysis was performed to investigate the outcomes of interest.

Results

Five RCTs with a total of 1,678 subjects were included. The 50 % responder rates were significantly greater in patients receiving 4, 8 and 12 mg perampanel versus placebo, with risk ratios of 1.54 (95 % CI 1.11-2.13), 1.80 (95 % CI 1.38-2.35) and 1.72 (95 % CI 1.17-2.52), respectively. There was no statistical evidence of a difference in seizure freedom between 8 or 12 mg perampanel and placebo. Of the five commonly reported TEAEs included, both dizziness and somnolence were statistically associated with 8 mg perampanel, whilst dizziness was statistically associated with 12 mg perampanel. Incidences of withdrawal due to adverse events were significantly higher in the 8 mg and 12 mg perampanel groups versus placebo.

Conclusion

The use of perampanel resulted in a statistically significant reduction of seizure frequency with respect to the 50 % responder rate in patients with partial-onset epilepsy. Perampanel is well tolerated at 4 mg and reasonably tolerated at 8 and 12 mg. Further clinical and pharmacovigilance studies are required to investigate the long-term efficacy and safety of perampanel in the management of other types of epilepsy.

SUBMITTER: Hsu WW

PROVIDER: S-EPMC3784051 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

Hsu Warrington W Q WW Sing C W CW He Ying Y Worsley Alan J AJ Wong Ian C K IC Chan Esther W EW

CNS drugs 20131001 10

<h4>Introduction</h4>Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design.<h4>Objective</h4>The ...[more]

PMID: 23918722

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Project description:Introduction: China has ~6 million patients with active epilepsy every year, around 60% of whom suffer from partial-onset seizures. Perampanel (PER) is a novel anti-epileptic drug for partial-onset seizures. PER has been included in the latest Chinese National Reimbursement Drug List (NRDL) in 2020. However, there is still a lack of evaluation evidence on the value of PER in China. Methods: This study selected a health system perspective. A Markov model was established to simulate the lifelong transition of different response levels and calculate the number of seizures in Chinese patients. Based on the utility value and mortality risk, the life years and quality-adjusted life years (QALYs) of patients using PER vs. lacosamide (LCM) were estimated. Efficacy data were derived from clinical trials and the literature. Cost data (in US dollars) included drug costs and medical service costs. A lifetime horizon was adopted. Health outcomes and costs were discounted at an annual discount rate of 5%. Deterministic sensitivity analysis, probability sensitivity analysis, and scenario analysis were performed. The impact of the inclusion of PER in the NRDL on the medical insurance budget over 3 years (2021-2023) was also estimated. Results: Cost-effectiveness analysis indicates that 8 mg/day of PER increases QALYs by 0.054 and saves costs by $2,390 compared with 400 mg/day of LCM. 4 mg/day of PER increases QALYs by 0.010 and saves costs by $860 compared with 200 mg/day of LCM. Deterministic sensitivity analysis reveals that utility value and the extreme discount rate are the factors with the greatest impact on the incremental cost-effectiveness ratio. Probabilistic sensitivity analysis and scenario analysis show that the results are robust. Budget impact analysis indicates that after inclusion of PER in the NRDL, the incremental budget would be $1.28, $2.83, and $4.56 million from 2021 to 2023, respectively, but covering more eligible epileptic patients in the same time (1,918, 4,287, and 8,983, respectively). Conclusion: PER (8 or 4 mg/day) is of relatively high value as an add-on therapeutic regimen for partial-onset seizures in China because of its dominate advantage of cost-effectiveness over LCM and acceptable budget impact.

Project description:Introduction:Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies. Aim:The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures. Evidence review:ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up. Conclusion:Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and was fairly well tolerated in adults with focal onset epilepsy. Starting treatment at 400 mg/day, followed by 400 mg increments every 7-14 days, could provide the optimal balance of efficacy and tolerability.

Project description:IntroductionFenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy.MethodsWe systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome.ResultsThree trials were identified and a total of 469 Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73-11.54) and 4.71 (95% CI 0.57-39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33-5.02) and 0.50 (95% CI 0.031-7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89-3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93-14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment.ConclusionFenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA.

Project description:ImportanceDespite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.ObjectiveTo evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.Data sourcesSystematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.Study selectionRandomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.Data extraction and synthesisData extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.Main outcomes and measuresShort-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.ResultsOf 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event-related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.Conclusions and relevanceThis study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

Dataset Information

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

Introduction

Objective

Methods

Results

Conclusion

Publications

Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

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