Alexandra Rohracher1, Georg Zimmermann1,2,3, Vicente Villanueva4, Iñigo Garamendi5, Josemir W Sander6,7,8, Tim Wehner6,9, Rohit Shankar10, Elinor Ben-Menachem11, Martin J Brodie12, Max C Pensel13, Giancarlo Di Gennaro14, Aude Maurousset15, Adam Strzelczyk16, Sylvain Rheims17, Attila Rácz13, Katja Menzler18, Vicente Bertol-Alegre19, Irene García-Morales20, Francisco Javier López-González21, Manuel Toledo22, Katherine J Carpenter23, Eugen Trinka1,3,24. 1. Department of Neurology, Christian Doppler Medical Center and Center for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria. 2. Department of Mathematics, Paris Lodron University, Salzburg, Austria. 3. Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria. 4. University Hospital and Polytechnic La Fe, Valencia, Spain. 5. Cruces University Hospital, Baracaldo, Spain. 6. NIHR University College London Hospitals Biomedical Research Centre, UCL Institute of Neurology, Queen Square, London, UK. 7. Chalfont Centre for Epilepsy, Chalfont St Peter, UK. 8. Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands. 9. Ruhr-Epileptology, Department of Neurology, Knappschaftskrankenhaus Bochum, Bochum, Germany. 10. Cornwall Partnership NHS Foundation Trust, Truro, UK. 11. Sahlgrenska Academy, University of Gothenburg, Gotheburg, Sweden. 12. Epilepsy Unit, West Glasgow ACH, Yorkhill, Glasgow, UK. 13. Department of Epileptology, University Hospital of Bonn, Bonn, Germany. 14. IRCCS NEUROMED (IS), Pozzilli, Italy. 15. University Hospital Bretonneau and INSERM U 930, Tours, France. 16. Epilepsy Center Frankfurt Rhine-Main, Goethe University, Frankfurt, Germany. 17. Department of Functional Neurology and Epileptology, Hospices Civils de Lyon and University of Lyon, Lyon, France. 18. Epilepsy Center Hessen, University Hospital Marburg, Marburg, Germany. 19. University Hospital Miguel Servet, Zaragoza, Spain. 20. Hospital Clinic San Carlos, Madrid, Spain. 21. University Hospital Complex Santiago, Santiago de Compostela, Spain. 22. University Hospital Vall d'Hebron, Barcelona, Spain. 23. Freelance Medical Writer, Hitchin, Hertfordshire, UK. 24. Institute of Public Health, Medical Decision Making and HTA, Private University for Health Sciences Medical Informatics and Technology, Hall in Tyrol, Austria.
Abstract
OBJECTIVE: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. METHODS: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. RESULTS: The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%. SIGNIFICANCE: Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel. Wiley Periodicals, Inc.
OBJECTIVE: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. METHODS: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. RESULTS: The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%. SIGNIFICANCE: Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel. Wiley Periodicals, Inc.
Authors: Robert T Wechsler; James Wheless; Muhammad Zafar; Graham R Huesmann; Marcelo Lancman; Eric Segal; Michael Chez; Sami Aboumatar; Anna Patten; Alejandro Salah; Manoj Malhotra Journal: Epilepsia Open Date: 2022-03-20