cenobamate的疗效很可能会超越其他第三代抗癫痫发作药吗？

The efficacy of cenobamate is likely to surpass that of other third-generation anti-epileptic seizure drugs. In clinical trials, cenobamate has shown a significant reduction in focal seizures, can improve patients' remission rate and seizure-free rate, and has good tolerability and safety.

The third-generation anti-epileptic drugs include many types of drugs, such as lamotrigine, oxcarbazepine, levetiracetam, etc. These drugs have good efficacy in treating epilepsy, but may have varying degrees of side effects and individual differences.

Cenobamate

is a new antiepileptic drug (ASM) approved in the United States for the treatment of focal-onset epilepsy in adults. In March 2021, the European Commission approved its use as an adjuvant treatment for adults with epilepsy who have focal-onset epilepsy that is not adequately controlled despite treatment with at least two ASMs.

cenobamate

Cenobate (CNB), a new treatment for ASD, showed unusually high efficacy in pivotal placebo-controlled randomized trials, with seizure-free rates sometimes exceeding 20% and improving quality of life in two studies.

Comparing the efficacy of cenobamate with other anti-epileptic drugs

Research purpose

The efficacy and safety of cenobate relative to other antiepileptic drugs (ASMs) have not been evaluated, and indirect treatment comparisons were conducted to determine whether adjuvant cenobamate compared with other adjuvant ASMs would increase the ≥50% response rate or odds ratio for discontinuation of ASM due to treatment-emergent adverse events (TEAEs).

research methods

A systematic literature review was conducted to identify randomized, double-blind, placebo-controlled trials (maintenance period ≥12 weeks) evaluating assisted spasticity in adults with uncontrolled focal epileptic seizures. Cenobamate was compared to a panel of seven other ASMs, branded ASM subgroups (brivaracetam, exibracetam acetate, parampanel) and older ASM subgroups (lamotrigine, levetiracetam, topiramate) at the FDA-recommended daily maintenance dose, all doses, maximum and minimum daily doses.

Research results

Twenty-one studies were eligible for analysis and showed that cenobamate had a higher placebo-adjusted response rate of ≥50% in FDA-RDMD. For response rates of ≥50%, there were no significant differences between RDMD FDA and RDMD FDA elderly ASMs.

No significant differences in response rates of ≥50% were found when comparing all doses and maximum/minimum doses of cenobamate to all seven brands and older ASM. Across four dose ranges, cenobamate demonstrated comparable TEAE abstinence rates with all seven ASMs, branded ASMs, and older ASMs.

Research conclusion

Compared with FDA-RDMD, patients receiving the seven ASMs and branded ASMs evaluated by FDA-RDMD were more likely to have a ≥50% reduction in seizures without increased treatment discontinuation due to TEAEs.

1. Initial dose: 12.5mg in the 1st and 2nd weeks, taken once a day.

2. Gradual increase: 25mg in the 3rd and 4th weeks, 50mg in the 5th and 6th weeks, 100mg in the 7th and 8th weeks, 150mg in the 9th and 10th weeks, also taken once a day.

3. Maintenance dose: 200mg in the 11th week and thereafter, taken once a day.

Summary

Cenobamate significantly reduces the frequency of focal epileptic seizures in adults, and the seizure freedom rate is relatively high. According to the results of multiple clinical trials, the efficacy of cenobamate is likely to surpass other third-generation anti-seizure drugs. However, individual differences, disease severity, drug interactions and other factors also need to be considered.

References:

Privitera M, Richy FF, Schabert VF. Indirect treatment comparison of cenobamate to other ASMs for the treatment of uncontrolled focal seizures. Epilepsy Behav. 2022 Jan;126:108429. doi: 10.1016/j.yebeh.2021.108429. Epub 2021 Dec 1. PMID: 34864380.

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