Effectiveness and safety of cenobamate in Lennox-Gastaut syndrome: A multicenter real-world study in Spain

Objective

Lennox-Gastaut syndrome (LGS) is a rare treatment-resistant epilepsy classed as developmental and epileptic encephalopathy (DEE). In this study we investigated the effectiveness and safety of cenobamate (CNB) as adjunctive therapy in adults with LGS under real-world conditions.

Methods

We conducted a retrospective analysis of clinical data collected from patients diagnosed with LGS who were prescribed CNB in 8 different sites. Data was sourced from patient clinical records. Effectiveness was evaluated by seizure type (total seizures, focal onset seizures, generalized tonic-clonic seizures [GTCS], drop seizures and atypical absence) and included ≥50 %, ≥75 %, ≥90 % responder rate and seizure freedom rate at 3, 6 and 12month visits. Changes in the number of co-antiseizure medication (co-ASM) were also analyzed. Safety/tolerability was monitored by documenting the incidence of adverse events (AE) and AEs leading to discontinuation.

Results

18 patients with LGS were included in the analysis (34.4 % women, mean age 25.2 years, and median number of seizures per month 195 (IQR: 12–1416)). The median of number of prior ASMs and concomitant ASMs were 12 (IQR: 8–16) and 3 (IQR: 2–6) respectively. Median CNB dosages/day was 200 mg (IQR: 50–350) at 3, 6 and 12 months. At 3, 6, and 12 months, 94.4 %, 94.4 % and 83.3 % of participants were retained on CNB treatment, respectively. At the last available visit, the seizure freedom rate was 12.5 %, ≥50 %, ≥75 %, ≥90 % responder rates were 46.2 %, 23.1 %, and 0 %, respectively. The number of co-ASMs was reduced in 36 % of patients. The percentage of patients with AEs and AEs leading to discontinuation was 0 %. The most frequent AEs were somnolence and bradypsychia or dizziness.

Conclusion

In this study, CNB demonstrated high effectiveness and good tolerability in patients with LGS when administered in adjuvancy in real-world practice after the failure of multiple ASMs. AEs were frequent but mostly mild-to-moderate.