Seizure-free days as a clinical outcome measure of reduced epilepsy burden: 5-year outcomes with cenobamate treatment

Abstract Background Sustained seizure freedom without intolerable adverse events is the main goal of epilepsy treatment, but may be challenging to achieve for some patients, particularly following the failure of multiple anti-seizure medications (ASMs). A majority of days without seizures is another important clinical outcome that can lead to meaningful improvement in quality of life. The objective of this post-hoc analysis was to evaluate the percentage of seizure-free days by responder groups during the open-label extension (OLE) of study C017 with a focus on patients who achieved near-seizure freedom that was sustained during the duration of the study (≥ 90%-< 100% responders group). The study also evaluated retention rates and the impact of concomitant antiseizure medications. Methods Study C017 (NCT01866111) was a double-blind, randomized, placebo-controlled, dose–response trial evaluating adults 18–70 years old who were taking 1–3 concomitant ASMs. Participants completed the 18-week double-blind treatment period and entered the OLE. This post-hoc analysis quantified the proportion of seizure-free days by responder category and by number and type of concomitant ASMs. The occurrence and severity of treatment-emergent adverse events during the OLE were also reported. Results Sixty (16.9%) of the 354 study participants were ≥ 90%-< 100% responders (median age 42.5 years, 46.7% [n = 28] female, median number of concomitant ASMs at baseline was 2). The study population also included 91 (25.7%) patients who were ≥ 50%-< 75% responders, 62 (17.5%) patients who were ≥ 75%-< 90% responders, and 13 (3.7%) patients who were 100% responders. The median duration of cenobamate exposure was 5.6 years for the ≥ 90%-< 100% responders; 1.8 years for the non-responders; 5.5 years for the ≥ 50%-< 75% responders; 5.5 years for the ≥ 75%-< 90% responders; and 5.6 years for the 100% responders. The percentage of seizure-free days during the entire OLE was 97.9% in the ≥ 90%-< 100% responder group, compared to 93.5% in the ≥ 75%-< 90% group and 83.9% in the ≥ 50%-< 75% group. The number and mechanism of action of concomitant ASMs did not meaningfully impact the proportion of days without seizures. The percentage of days with seizures in the ≥ 90%-< 100% responder group declined from 33.2% at baseline to 1.2% at Year 5. At Year 5, the ≥ 90%-< 100% responder group had a high retention rate (90%). The most commonly occurring adverse events were dizziness, somnolence, and headache. Conclusions Participants taking cenobamate who achieved ≥ 90%-< 100% responder rates were seizure-free for nearly 98% of days during the 5 years of the OLE. These results suggest that a high reduction of seizure burden can be achieved and maintained by many people with epilepsy taking cenobamate.