Efficacy and safety of cenobamate in developmental and epileptic encephalopathies: A systematic review and meta-analysis

To evaluate the efficacy and safety of cenobamate in developmental and epileptic encephalopathies (DEE) through systematic review and meta-analysis.

We systematically searched electronic databases for studies reporting cenobamate outcomes in DEE. Primary outcome was the proportion of patients achieving ≥50 % seizure reduction. Secondary outcomes included seizure freedom, treatment retention, and treatment-emergent adverse events (TEAEs). Study quality was assessed using the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool. Generalized linear mixed-model (GLMM) meta-analyses with logit transformation were performed. Between-study heterogeneity was assessed using I² statistics. Leave-one-out sensitivity analysis identified influential studies. Meta-regression explored associations between study characteristics and outcomes. Evidence quality was evaluated using GRADE criteria.

Fourteen studies involving 368 DEE patients were included; individual studies reported mean ages ranging from 8.7 to 42 years and follow-up durations of 3 to 24 months. Patients had extensive treatment histories (8-15 prior antiseizure medications). The pooled ≥50 % responder rate was 56.8 % (95 % CI: 41.9-70.6 %; I² = 74.9 %). Sensitivity analysis excluding four influential studies produced a similar estimate (63.4 %, 95 % CI: 46.5-77.6 %) with no heterogeneity. Seizure freedom was achieved in 10.3 % (95 % CI: 6.6-15.7 %; I² = 21.3 %). Treatment retention was high at 88.6 % (95 % CI: 66.9-96.7 %), though longitudinal data showed decline over time. TEAEs occurred in 60.3 % (95 % CI: 53.5-66.7 %), most often somnolence, dizziness, and ataxia, typically manageable with dose adjustments. No cases of DRESS were reported. Meta-regression found no significant association between age, follow-up duration, or prior/current antiseizure medication burden and treatment response.

Cenobamate demonstrates promising efficacy in highly refractory DEEs, with over half of patients achieving ≥50 % seizure reduction and ∼10 % attaining seizure freedom despite extensive prior treatment failures. The high retention rate and manageable safety profile support its use as a valuable therapeutic option in this difficult-to-treat population.