Skuteczność i bezpieczeństwo cenobamianu u dzieci i młodzieży z oporną na leki epilepsją: przegląd systematyczny, metaanaliza i meta-regresja
Real-world effectiveness and safety of cenobamate in children and adolescents with drug-resistant epilepsy: a systematic review, meta-analysis, and meta-regression
W skrócie
Badacze przeanalizowali dostępne dane z 16 badań dotyczących stosowania cenobamianu (nowego leku przeciwpadaczkowego) u 720 dzieci i młodzieży, których padaczka nie reaguje na tradycyjne leki. Okazało się, że około 60 procent pacjentów osiągnęło znaczną zmianę - przynajmniej o połowę mniej napadów, a efekty uboczne leku zaobserwowano u połowy dzieci. Jednak do bardziej pewnych wniosków konieczne są badania obserwacyjne na większą skalę, ponieważ dotychczasowe dane pochodziły głównie ze starszych dokumentacji medycznej.
Oryginalny abstract (angielski)
BACKGROUND AND OBJECTIVES: Cenobamate is a third-generation antiseizure medication (ASM) approved for focal-onset seizures in adults; pediatric use remains off-label and supported primarily by retrospective studies. We conducted a systematic review, meta-analysis, and meta-regression to evaluate the real-world effectiveness and safety of adjunctive cenobamate in pediatric drug-resistant epilepsy (DRE). METHODS: We conducted a PRISMA 2020-compliant systematic review and meta-analysis (PROSPERO: CRD420261475361) of real-world studies including patients ≤18 years with DRE. Single-arm proportions were pooled using random-effects generalized linear mixed models. Heterogeneity was assessed using I and τ. Pre-specified random-effects meta-regression explored study-level moderators of ≥50 % seizure reduction. Risk of bias was assessed using the JBI Critical Appraisal Checklist for Case Series. RESULTS: Sixteen retrospective cohorts comprising 720 pediatric patients from 10 countries were included. The pooled proportion achieving ≥50 % seizure reduction was 59.9 % (95 % CI, 51.4 %-67.9 %; 95 % prediction interval, 30.2 %-83.8 %; I = 68.2 %). Pooled estimates were 41.9 % (95 % CI, 26.4-59.2 %) for >75 % seizure reduction, 18.6 % (95 % CI, 12.3-27.1 %) for seizure freedom, and 49.9 % (95 % CI, 44.1-55.7 %) for any adverse effect. Leave-one-out analysis showed that no individual study disproportionately influenced the pooled ≥50 % seizure-response proportion (58.3-61.9 %). Visual and regression-based assessments did not detect marked funnel-plot asymmetry or an association between study size and effect estimates. No pre-specified moderator, including age, prior ASM burden, cenobamate dose, follow-up duration, focal epilepsy, clobazam exposure, or etiology, was significantly associated with response. CONCLUSIONS: Approximately six in ten pediatric patients with DRE achieved ≥50 % seizure reduction with cenobamate. However, persistent unexplained heterogeneity and exclusively retrospective evidence limit subgroup-level inference. Prospective individual-patient-data registries with standardized outcome and dosing measures are needed to better define effectiveness, safety, and predictors of response in pediatric populations.