TY - JOUR
T1 - PROVE
T2 - Retrospective, non-interventional, Phase IV study of perampanel in real-world clinical care of patients with epilepsy
AU - Wechsler, Robert T.
AU - Wheless, James
AU - Zafar, Muhammad
AU - Huesmann, Graham R.
AU - Lancman, Marcelo
AU - Segal, Eric
AU - Chez, Michael
AU - Aboumatar, Sami
AU - Patten, Anna
AU - Salah, Alejandro
AU - Malhotra, Manoj
N1 - Robert T. Wechsler has been a clinical trial investigator for Aquestive, Biogen, Cavion, Cerevel, Eisai, Engage Pharma, Greenwich Biosciences, Lundbeck, Otsuka, Pfizer, SK Life Science, Sunovion, UCB Pharma, Xenon, and Zogenix; has served on advisory boards and/or carried out consulting work for Brain Sentinel, Cerevel, Eisai, Engage Pharma, Greenwich Biosciences, Lundbeck, Otsuka, SK Life Science, Sunovion, and UCB Pharma; has received speaker bureau honoraria from Aquestive, Eisai, Greenwich Biosciences, LivaNova, Neurelis, SK Life Science, Sunovion, and UCB Pharma; and is a member of the Epilepsy Study Consortium. James Wheless has received grant support from Aquestive, Eisai, Greenwich, INSYS Inc, LivaNova, Mallinckrodt, Neurelis, NeuroPace, the Shainberg Foundation, and West; has served as a consultant for Aquestive, BioMarin, Eisai, Greenwich, Mallinckrodt, Neurelis, NeuroPace, Shire, Supernus, and Zogenix; and has received speaker bureau honoraria from BioMarin, Eisai, Greenwich, LivaNova, Mallinckrodt, and Supernus. Muhammad Zafar has received research support from and has been a consultant for Eisai, LivaNova, and Marinus Pharmaceuticals; has received research support from Stoke Therapeutics and UCB Pharma; and has been a consultant for Mallinckrodt. Graham R. Huesmann has no disclosures to make in relation to this work. Marcelo Lancman has received research grant support from Eisai. Eric Segal has received honoraria from Eisai, GW Pharma, Lundbeck, and Zogenix. Michael Chez has served as a consultant for, and has received grant support and/or speaker or advisory honoraria from, Aquestive, Eisai, GW Pharma, Mallinckrodt Zogenix, Marinus, and UCB Pharma. Sami Aboumatar has served on advisory boards and/or has carried out consulting work for Eisai and Sunovion. Anna Patten is an employee of Eisai Europe Ltd. Alejandro Salah is a former employee of Eisai Inc. Manoj Malhotra is an employee of Eisai Inc. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.
The authors would like to thank the study participants. The PROVE study (NCT03208660) was funded by Eisai Inc. Medical writing support, under the direction of the authors, was provided by David Pertab, and Daniela DiBiase, of CMC AFFINITY, McCann Health Medical Communications, funded by Eisai Inc., in accordance with Good Publication Practice (GPP3) guidelines. The data reported in this paper have previously been presented at the 73rd Annual Meeting of the American Epilepsy Society, Baltimore, MD, USA, December 6-10, 2019.
The authors would like to thank the study participants. The PROVE study (NCT03208660) was funded by Eisai Inc. Medical writing support, under the direction of the authors, was provided by David Pertab, and Daniela DiBiase, of CMC AFFINITY, McCann Health Medical Communications, funded by Eisai Inc., in accordance with Good Publication Practice (GPP3) guidelines. The data reported in this paper have previously been presented at the 73rd Annual Meeting of the American Epilepsy Society, Baltimore, MD, USA, December 6‐10, 2019.
PY - 2022/6
Y1 - 2022/6
N2 - Objective: To assess retention, dosing, efficacy, and safety of perampanel in a large cohort of patients with epilepsy during routine clinical care. Methods: PROVE was a retrospective, non-interventional Phase IV study (NCT03208660). Data were obtained retrospectively from the medical records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinicians' recommendation. Retention rate was the primary efficacy endpoint. Secondary efficacy endpoints included median percent changes in seizure frequency per 28 days from baseline, seizure-freedom rate, and overall investigator impression of seizure effect. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs). Efficacy and safety were also assessed according to baseline use of enzyme-inducing antiseizure medications (EIASMs). Results: Overall, 1703 patients were enrolled and included in the Safety Analysis Set (SAS; ≥1 baseline EIASMs, n = 358 [21.0%]; no baseline EIASMs, n = 1345 [79.0%]). Mean (standard deviation [SD]) cumulative duration of exposure to perampanel was 17.4 (15.7) months; mean (SD) daily perampanel dose was 5.6 (2.7) mg. The most frequent perampanel titration intervals were weekly (23.4%) and every 2 weeks (24.7%). Across the SAS, 24-month retention rate was 48.1% (n = 501/1042). Based on overall investigator impression at the end of treatment, 51.9%, 35.8%, and 12.3% of patients in the SAS experienced improvement, no change, or worsening of seizures, respectively. TEAEs occurred in 704 (41.3%) patients; 79 (4.6%) had serious TEAEs. The most common TEAE was dizziness (7.3%). There was some variation in efficacy according to EIASM use, while retention rates and safety were generally consistent. Significance: In this final analysis of >1700 patients with epilepsy receiving perampanel in routine clinical care, favorable retention and sustained efficacy were demonstrated for ≥12 months.
AB - Objective: To assess retention, dosing, efficacy, and safety of perampanel in a large cohort of patients with epilepsy during routine clinical care. Methods: PROVE was a retrospective, non-interventional Phase IV study (NCT03208660). Data were obtained retrospectively from the medical records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinicians' recommendation. Retention rate was the primary efficacy endpoint. Secondary efficacy endpoints included median percent changes in seizure frequency per 28 days from baseline, seizure-freedom rate, and overall investigator impression of seizure effect. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs). Efficacy and safety were also assessed according to baseline use of enzyme-inducing antiseizure medications (EIASMs). Results: Overall, 1703 patients were enrolled and included in the Safety Analysis Set (SAS; ≥1 baseline EIASMs, n = 358 [21.0%]; no baseline EIASMs, n = 1345 [79.0%]). Mean (standard deviation [SD]) cumulative duration of exposure to perampanel was 17.4 (15.7) months; mean (SD) daily perampanel dose was 5.6 (2.7) mg. The most frequent perampanel titration intervals were weekly (23.4%) and every 2 weeks (24.7%). Across the SAS, 24-month retention rate was 48.1% (n = 501/1042). Based on overall investigator impression at the end of treatment, 51.9%, 35.8%, and 12.3% of patients in the SAS experienced improvement, no change, or worsening of seizures, respectively. TEAEs occurred in 704 (41.3%) patients; 79 (4.6%) had serious TEAEs. The most common TEAE was dizziness (7.3%). There was some variation in efficacy according to EIASM use, while retention rates and safety were generally consistent. Significance: In this final analysis of >1700 patients with epilepsy receiving perampanel in routine clinical care, favorable retention and sustained efficacy were demonstrated for ≥12 months.
KW - antiseizure medication
KW - dosing
KW - long-term observational
KW - postmarketing
KW - seizure
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U2 - 10.1002/epi4.12575
DO - 10.1002/epi4.12575
M3 - Article
C2 - 34942053
AN - SCOPUS:85126454333
SN - 2470-9239
VL - 7
SP - 293
EP - 305
JO - Epilepsia Open
JF - Epilepsia Open
IS - 2
ER -