Cenobamate: real-world data from a retrospective multicenter study

Journal of Neurology, vol. 271, pp. 6596–6604

Abstract

BACKGROUND: Clinical trials have shown that cenobamate (CNB) is an efficacious and safe anti-seizure medication (ASM) for drug-resistant focal epilepsy. Here, we analyzed one of the largest real-world cohorts, covering the entire spectrum of epilepsy syndromes, the efficacy and safety of CNB, and resulting changes in concomitant ASMs. METHODS: We conducted a retrospective observational study investigating CNB usage in two German tertiary referral centers between October 2020 and June 2023 with follow-up data up to 27 months of treatment. Our primary outcome was treatment response. Secondary outcomes comprised drug response after 12 and 18 months, seizure freedom rates, CNB dosage and retention, adverse drug reactions (ADRs), and changes in concomitant ASMs. RESULTS: 116 patients received CNB for at least two weeks. At 6 months, 98 patients were eligible for evaluation. Thereof 50% (49/98) were responders with no relevant change at 12 and 18 months. Seizure freedom was achieved in 18.4% (18/98) at 6 months, 16.7% (11/66), and 3.0% (1/33) at 12 and 18 months. The number of previous ASMs did not affect the seizure response rate. Overall, CNB was well-tolerated, however, in 7.7% (9/116), ADRs led to treatment discontinuation. The most frequent changes of concomitant ASMs included the discontinuation or reduction of sodium channel inhibitors, clobazam reduction, and perampanel discontinuation, while brivaracetam doses were usually left unchanged. CONCLUSIONS: CNB proved to be a highly effective and generally well-tolerated ASM in patients with severe drug-resistant epilepsy, comprising a broad array of epilepsy syndromes beyond focal epilepsy.

Authors 11

1. Stephan Lauxmann corresponding

   Hertie Institute for Clinical Brain Research · University of Tübingen

   Affiliation as printed

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany. stephan.lauxmann@uni-tuebingen.de

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

2. Jan Heckelmann Aachen Department of Epileptology and Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany

3. Florian P. Fischer Aachen Department of Epileptology and Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany

4. Melanie Schreiber

   Hertie Institute for Clinical Brain Research · University of Tübingen

   Affiliation as printed

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

5. Elisabeth Schriewer Aachen Department of Epileptology and Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany

6. Guido Widman Aachen Department of Epileptology and Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany

7. Yvonne G. Weber Aachen Department of Epileptology and Neurology

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany

8. Holger Lerche

   Hertie Institute for Clinical Brain Research · University of Tübingen

   Affiliation as printed

   Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

9. Michael Alber

   University Children's Hospital Tübingen · University of Tübingen

   Affiliation as printed

   Department of Pediatric Neurology and Developmental Medicine, University Children's Hospital, Tuebingen, Germany

10. Sigrid Schuh‐Hofer

    Hertie Institute for Clinical Brain Research · University of Tübingen

    Affiliation as printed

    Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany

11. Stefan Wolking Aachen Department of Epileptology and Neurology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Department of Epileptology and Neurology, RWTH Aachen University Hospital, Aachen, Germany