Edoardo Ferlazzo1,2, Giorgia Giussani3, Sara Gasparini1,2, Elisa Bianchi3, Vittoria Cianci2, Vincenzo Belcastro4, Roberto Cantello5, Gionata Strigaro5, Matilde Lazzari5, Amedeo Bianchi6, Martina Guadagni6, Silvia Pradella6, Angela La Neve7, Teresa Francavilla7, Nicola Pilolli7, Paola Banfi8, Francesco Turco8, Marta Piccioli9, Luigi Polidori9, Teresa Anna Cantisani10, Rossella Papetti10, Michela Cecconi10, Elisabetta Pupillo3, Emilio Davide Arippol3, Gabriele Enia3, Sabrina Neri1,2, Umberto Aguglia11,12, Ettore Beghi3. 1. Department of Medical and Surgical Sciences, "Magna Græcia" University of Catanzaro, Catanzaro, Italy. 2. Regional Epilepsy Centre, Great Metropolitan Hospital, Via Melacrino, 89100, Reggio Calabria, Italy. 3. Laboratory of Neurological Disorders, Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. 4. Neurology Unit, Maggiore Hospital, ASST Lodi, Lodi, Italy. 5. Neurology Unit, Department of Translational Medicine, University of Piemonte Orientale, Azienda Ospedaliero-Universitaria "Maggiore Della Carità", Novara, Italy. 6. Department of Neurology and Epilepsy Centre, San Donato Hospital, Arezzo, Italy. 7. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy. 8. Department of Emergency, Medicine Epilepsy Center, Neurology Unit, Circolo Hospital, Varese, Italy. 9. UOC Neurology, PO San Filippo Neri, ASL Roma 1, Rome, Italy. 10. Neurophysiopathology, Perugia Hospital, Perugia, Italy. 11. Department of Medical and Surgical Sciences, "Magna Græcia" University of Catanzaro, Catanzaro, Italy. aguglia@unicz.it. 12. Regional Epilepsy Centre, Great Metropolitan Hospital, Via Melacrino, 89100, Reggio Calabria, Italy. aguglia@unicz.it.
Abstract
PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.
PURPOSE: To establish whether a slow or a rapid withdrawal of antiepileptic monotherapy influences relapse rate in seizure-free adults with epilepsy and calculates compliance and differences in the severity of relapses, based on the occurrence of status epilepticus, seizure-related injuries, and death. METHODS: This is a multicentre, prospective, randomized, open label, non-inferiority trial in people aged 16 + years who were seizure-free for more than 2 years. Patients were randomized to slow withdrawal (160 days) or rapid withdrawal (60 days) and were followed for 12 months. The primary outcome was the probability of a first seizure relapse within the 12-months follow-up. The secondary outcomes included the cumulative probability of relapse at 3, 6, 9, and 12 months. A non-inferiority analysis was performed with non-inferiority margin of - 0.15 for the difference between the probabilities of seizure recurrence in slow versus rapid withdrawal. RESULTS: The sample comprised 48 patients, 25 randomized to slow withdrawal and 23 to rapid withdrawal. Median follow-up was 11.9 months. In the intention-to-treat population, 3 patients in the slow-withdrawal group and 1 in the rapid withdrawal group experienced seizure relapses. The corresponding probabilities of seizure recurrence were 0.12 for slow withdrawal and 0.04 for rapid withdrawal, giving a difference of 0.08 (95% CI - 0.12; 0.27), which is entirely above the non-inferiority margin. No patients developed status epilepticus and seizure-related injuries or died. Risks were similar in the Per-Protocol population. CONCLUSIONS: Seizure-relapse rate after drug discontinuation is lower than in other reports, without complications and unrelated to the duration of tapering.
Authors: Ettore Beghi; Giorgia Giussani; Salvatore Grosso; Alfonso Iudice; Angela La Neve; Francesco Pisani; Luigi M Specchio; Alberto Verrotti; Giuseppe Capovilla; Roberto Michelucci; Gaetano Zaccara Journal: Epilepsia Date: 2013-10 Impact factor: 5.864