Efficacy and Tolerability Assessment of Cenobamate Treatment After Failure of 1 or 2 Asms
Abstract number :
2.268
Submission category :
4. Clinical Epilepsy / 4C. Clinical Treatments
Year :
2024
Submission ID :
15
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Abigail Heath, BS – Mid Atlantic Epilepsy and Sleep Center
Dylan Huynh, BS – Mid Atlantic Epilepsy and Sleep Center
Ivana Tyrlikova, MD – Mid Atlantic Epilepsy and Sleep Center
Pavel Klein, MD – Mid Atlantic Epilepsy and Sleep Center
Salman Hashmi, MBBS, MS – Mid Atlantic Epilepsy and Sleep Center
Rationale: Cenobamate (CNB) is effective in treatment of patients with established drug refractory epilepsy (DRE). It may therefore be effective in early refractory epilepsy. We evaluated patients with early-stage DRE (2 failed ASMs) and patients with a high risk of DRE (1 ASM failed for lack of efficacy [LOE]).
Methods: This was a prospective open-label study. Patients were treated with CNB as 2nd or 3rd ASM, after either (1) failure of 2 ASMs or (2) failure of 1 ASM with high risk of developing DRE (ASM failure for LOE). Seizure diaries were kept before and during CNB treatment. CNB was titrated up to seizure freedom, side effects, or maximum CNB dose of 450mg/day. ≥50%-, 75%-, 90%- and 100% (0 seizures) responder rates (RR, seizure reduction from baseline) were assessed for the whole treatment and maintenance treatment periods, defined as treatment lasting ≥1 month after the last maximum CNB dose adjustment at ≥50mg/d. Patients who stopped CNB before 50mg/d or were lost to follow-up before reaching the maximum tolerated dose were deemed non-responders. Safety and tolerability measures included treatment-emergent adverse events (TEAEs), discontinuation due to TEAEs, and SAEs.
Results: 40 patients started CNB (62.5%F, mean age 41.9Y [range 17-75 y]): 23 (57.5%) as 2nd ASM and 17 (42.5%) as 3rd ASM. Commonest etiologies were cryptogenic (52.5%), TBI (17.5%), ante/peri/postnatal injury (5%), and developmental/congenital (5%). 39 patients had focal and 1 generalized epilepsy.
Efficacy: 5 patients (12.5%) stopped at < 6 months of treatment. Median CNB whole- and maintenance treatment durations were 15.2 and 8.3 months (ranges: 4-109 and 2–53). Median maintenance dose was 200mg/d (range 150-450).
The whole group:
11/40 (27.5 %) patients were seizure-free during the whole treatment, and 22/40 (55%) during the maintenance treatment periods. ≥90% seizure reduction occurred in 50% (n=20)and 62.5% (n=25) during the whole- and maintenance treatment periods. 11 patients (27.5%) were seizure free for ≥12 months at last follow up.
CNB as 2nd ASM cohort:
10/23 patients (43.5%) were seizure-free during the whole treatment, and 15/23 (65.2%) during the maintenance treatment.
CNB as 3rd ASM cohort:
1/17 patients (5.9%)and 7/17 (41.2%) were seizure-free during the whole treatment and maintenance treatment periods.
Reduced and discontinued ASMs:
Patients had median 1 (range 1-2) concomitant ASMs at the time of CNB initiation. 25% of patients (n=10) stopped ≥1 concomitant ASMs after CNB initiation; 50% (n=20) reduced the dose of ≥1 concomitant ASMs. 5/40 patients (12.5%) were on CNB monotherapy at the time of analysis.
Adverse Events:
Main TEAEs affecting ≥5% of patients are shown in Table 1; cognitive and psychiatric TEAEs in Table 2. Most TEAEs were mild to moderate. 5 (12.5%) patients stopped due to TEAEs: rash (n=2), somnolence and ataxia (n=1), elevated LFTs (n=1), and depression + aggression (n=1). There was no DRESS. One patient died of SUDEP, aged 30, seizure free 9 months after starting CNB, on 200mg/d.
Conclusions: CNB as 2nd or 3rd ASM was generally safe and well tolerated in early DRE or DRE-high risk patients. A significant proportion of patients achieved seizure freedom.
Funding: N/A
Clinical Epilepsy