Comparative Effectiveness of Brivaracetam, Cenobamate, Lacosamide, and Perampanel in Focal Epilepsy
- 4일 전
- 4분 분량
2026년 02월09일
JAMA Neurol. Published online: February 9, 2026
DOI:10.1001/jamaneurol.2025.5625
Abstract
Importance Treatment decisions in drug-resistant focal epilepsy remain largely empirical, as direct comparative evidence among newer antiseizure medications (ASMs) is limited. Real-world data can complement randomized clinical trials by providing insights into long-term effectiveness and safety across diverse populations.
Objective To compare effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy.
Design, Setting, and Participants This was a multicenter pooled analysis of 4 previously conducted retrospective real-world medical record–review studies (January 2017-January 2024). Included were adult patients (aged ≥16 years) with drug-resistant focal epilepsy, as defined by the International League Against Epilepsy. Participants were recruited from 71 epilepsy centers.
Exposures Add-on treatment with brivaracetam, cenobamate, lacosamide, or perampanel.
Main Outcomes and Measures The primary outcome was the responder rate at 6 months, defined as greater than or equal to 50% seizure frequency reduction from baseline. Secondary outcomes included 12-month responder rate, seizure freedom (≥3 months at 6 months and ≥6 months at 12 months), and 12-month ASM retention. Safety was assessed by incidence of adverse effects. Generalized linear mixed models adjusted for demographic and clinical covariates were used to compare treatment outcomes, with cenobamate as reference ASM.
Results Of 2386 ASM prescriptions screened, 1993 prescriptions from 1949 patients (1036 of 1947 female [53.2%]; sex information was missing in 0.1% of prescriptions) with a median (IQR) age of 42 (29-55) years at ASM prescription, met inclusion criteria and were included in the pooled analysis. Brivaracetam accounted for 953 prescriptions (47.8%), followed by perampanel (607 [30.5%]), lacosamide (241 [12.1%]), and cenobamate (192 [9.6%]). After adjustment, cenobamate demonstrated significantly higher odds of 50% or greater response at 6 months compared with brivaracetam (odds ratio [OR], 0.18; 95% CI, 0.12-0.28; P < .001), perampanel (OR, 0.26; 95% CI, 0.16-0.42; P < .001), and lacosamide (OR, 0.29; 95% CI, 0.17-0.49; P < .001). Results were consistent for secondary effectiveness outcomes at 12 months, with cenobamate outperforming other ASMs in terms of 50% or greater response and seizure freedom. Cenobamate was associated with the highest rate of adverse effects during follow-up (111 [57.8%]), and lacosamide was associated with the lowest (35 [14.8%]). Cenobamate was associated with a higher likelihood of treatment retention at 12 months compared with brivaracetam (OR, 0.43; 95% CI, 0.26-0.69; P < .001) and perampanel (OR, 0.56; 95% CI, 0.32-0.99; P = .047), with no significant difference vs lacosamide (OR, 0.81; 95% CI, 0.41-1.59; P = .53).
Conclusions and Relevance These study findings suggest superior effectiveness of cenobamate over brivaracetam, lacosamide, and perampanel in adults with drug-resistant focal epilepsy in a large real-world setting.
Key Points
Question What is the comparative effectiveness and safety of brivaracetam, cenobamate, lacosamide, and perampanel as adjunctive therapies in adults with drug-resistant focal epilepsy?
Findings In this pooled analysis of real-world medical record–review studies of 1949 patients with drug-resistant focal epilepsy, cenobamate was associated with higher responder rates and seizure freedom at 6 and 12 months compared with brivaracetam, lacosamide, and perampanel, albeit with a higher incidence of adverse effects.
Meaning These results suggest that cenobamate offers superior long-term effectiveness over other newer ASMs in drug-resistant focal epilepsy, although its increased risk of adverse effects should be carefully weighed in clinical decision-making.
요약
· 중요성 : 약물 내성 초점성 간질에서 치료 결정은 여전히 경험적(empirical)인 경우가 많으며, 새로운 항경련제(ASM)들 간의 직접 비교 근거는 제한적이다. 실제 진료(real-world) 데이터는 다양한 환자군에서 장기적인 효과와 안전성에 대한 정보를 제공함으로써 무작위 임상시험을 보완할 수 있다.
· 목적 : 약물 내성 초점성 간질 성인 환자에서 보조요법으로 사용된 brivaracetam, cenobamate, lacosamide, perampanel의 효과와 안전성을 비교하는 것.
· 설계, 환경 및 참가자 :
-연구 유형: 4개의 후향적 실제 진료 데이터 연구를 통합한 다기관 분석
-연구 기간: 2017년 1월 ~ 2024년 1월
-참여 센터: 총 71개 간질센터에서 환자 모집
-대상자: 만 16세 이상 성인
국제항간질연맹(ILAE) 기준의 약물 내성 초점성 간질 환자
· 노출 다음 항경련제의 추가 요법(add-on therapy):
-brivaracetam
-cenobamate
-lacosamide
-perampanel
· 주요 평가지표
-1차 평가 지표:
▪ 6개월 반응률 (responder rate)
→ 발작 빈도 ≥50% 감소
-2차 평가 지표:
▪ 12개월 반응률 (responder rate)
▪ 발작 완전 소실(seizure freedom)
→6개월 시점: ≥3개월 무발작
→12개월 시점: ≥6개월 무발작
▪ 12개월 약물 유지율 (retention)
-안전성 평가
▪ 이상반응 발생률
-분석 방법
▪ 인구학적/임상적 변수 보정 후
generalized linear mixed model 사용
▪ 기준 약물: cenobamate
· 결과 :
-연구 대상
▪ 총 2,386건 중 1,993 처방 (1,949명 환자) 포함
▪ 여성: 53.2%
▪ 중앙 연령: 42세 (IQR 29–55)
-약물분포
▪ brivaracetam: 953건 (47.8%)
▪ perampanel: 607건 (30.5%)
▪ lacosamide: 241건 (12.1%)
▪ cenobamate: 192건 (9.6%)
-효과비교
cenobamate가 모든 약물 대비 우수
▪vs brivaracetam: OR 0.18 (P<0.001)
▪vs perampanel: OR 0.26 (P<0.001)
▪vs lacosamide: OR 0.29 (P<0.001)
-12개월 결과
▪ 반응률 및 발작 소실 모두에서cenobamate가 가장 우수
-안전성
▪ 이상반응 가장 높음: cenobamate (57.8%)
▪ 가장 낮음: lacosamide (14.8%)
-약물 유지율 (12개월)
Cenobamate가
▪ brivaracetam보다 높음 (OR 0.43, P<0.001)
▪ perampanel보다 높음 (OR 0.56, P=0.047)
▪ lacosamide와는 차이 없음
· 결론 및 의의 : 이 연구는 실제 임상 환경에서 cenobamate가 brivaracetam, lacosamide, perampanel보다 우수한 효과를 보임을 시사한다. 다만, 이상반응 발생률은 더 높다는 점을 고려해야 한다.
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