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Rapid versus slow withdrawal of antiepileptic monotherapy in 2-year seizure-free adult patients with epilepsy (RASLOW) study: a pragmatic multicentre, prospective, randomized, controlled study

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Abstract

Antiepileptic drug withdrawal may be an option for patients who have been seizure free for some years. The best withdrawal rate is questionable; in particular, it is unknown whether “rapid” withdrawal is associated with a higher risk of relapse as compared to “slow” withdrawal. We aim to establish if a slow or a rapid withdrawal schedule of antiepileptic monotherapy influences relapse rate in adult patients with focal or generalized epilepsy who have been seizure free for at least 2 years. This multicentre, prospective, randomized controlled study will enroll adult patients with focal or generalized epilepsy, who are seizure free on monotherapy. Patients will be randomized to a slow (160 days) or a rapid (60 days) schedule. Follow-up will last 1 year after randomization. The primary endpoint is the time to seizure relapse; secondary endpoints are compliance to the assigned schedule, occurrence of status epilepticus, of seizure-related injuries and mortality. A sample size of 350 patients has been planned. Univariate and multivariate analysis by Kaplan–Meier curves and Cox regression (primary endpoint) and by logistic regression (secondary endpoint) will be performed. The present study should contribute to better define the best withdrawal period for AED treatment in adult patients with epilepsy.

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Acknowledgments

Elio Agostoni (Department of Neurology and Stroke Unit, Niguarda Ca’ Granda Hospital, Milan, Italy), Paolo Aloisi, Nicola Cimini, Alfonso Marrelli, Claudio Martinazzo (Neuroscience Department and Neurophysiopathology Unit, L’Aquila, Italy), Harald Ausserer, Francesco Brigo (Department of Neurology, Franz Tappeiner Hospital, Merano, Italy), Vincenzo Belcastro (Neurology Unit, Sant’Anna Hospital, Como, Italy), Simone Beretta, Jacopo Di Francesco (Neurology Unit, “San Gerardo” Hospital, Monza, Italy), Paolo Benna, Elisa Montalenti (Neuroscience Department, University of Turin, Italy), Amedeo Bianchi, Martina Guadagni (Department of Neurology and Epilepsy Centre, San Donato Hospital, Arezzo, Italy), Giorgio Bono (Department of Neurology, Circolo Hospital, University of Insubria, Varese, Italy), Roberto Campostrini (Epilepsy Center, Misericordia e Dolce Hospital, Prato, Italy), Roberto Cantello, Gionata Strigaro, Claudia Varrasi (Neurology Unit, Novara Hospital, Italy), Teresa Cantisani, Michela Cecconi, Rossella Papetti, (Neurophysiopathology Unit, Azienda Ospedaliera Perugia, Perugia, Italy), Filippo Dainese, Francesco Paladin (Neurologic Unit, SS. Giovanni e Paolo Hospital, Venezia, Italy), Giovanni De Maria (Neurology Unit, “Spedali Civili” Hospital, Brescia, Italy), Roberto De Simone (Neurologic Unit, Epilepsy Center, Sant’Eugenio Hospital, Rome, Italy), Carlo Di Bonaventura, Anna Teresa Giallonardo, Oriano Mecarelli (Department of Neurological Sciences, “La Sapienza” University, Rome, Italy), Maurizio Elia (IRCCS OASI, Troina, Italy), Daniela Fatuzzo, Loretta Giuliano, Vito Sofia (Department “GF.Ingrassia”, Neurologic Clinic, University of Catania, Italy), Monica Ferlisi, Tiziano Zanoni (Division of Neurology, University Hospital, Verona, Italy), Teresa Francavilla, Angela La Neve (Epilepsy Center, Neurologic Clinic, Policlinico di Bari, Bari, Italy), Carlo Andrea Galimberti (IRCCS Mondino, Pavia, Italy), Antonio Gambardella, Angelo Labate, Laura Mumoli (Neurology Clinic, Magna Graecia University, Catanzaro, Italy), Paola Gambaro, Silvia Rosa (Neurology Unit, Sacco Hospital, Milan, Italy), Filippo S. Giorgi, Alfonso Iudice, Chiara Pizzanelli (Department of Experimental and Clinical Medicine, Section of Neurology, University of Pisa, Pisa, Italy), Gabriele Greco, Mario Santangelo (Department of Neurology, Ospedale di Carpi, Modena, Italy), Francesca Izzi, Claudio Liguori, Grazia Marciani, Fabio Placidi, Andrea Romigi (Neuroscience Department and Neurologic Clinic, Tor Vergata University, Rome, Italy), Adriana Magaudda, Francesco Pisani (Department of Neurosciences, University of Messina, Messina, Italy), Daniela Marino, Raffaele Rocchi, Gianpaolo Vatti (Neurologic Institute, University of Siena, Italy), Walter Merella (Department of Neurology, “G. Brotzu” Hospital, Cagliari, Italy), Roberto Michelucci (IRCCS Bellaria Hospital, Bologna, Italy), Fabio Minicucci (IRCSS S. Raffaele, Milan, Italy), Fabrizio Monti (Neurologic Unit, Riuniti Hospital, Trieste, Italy), Leandro Provinciali (Experimental and Clinical Medicine Department—Clinical Neuroscience Section, Ancona, Italy), Marina Saladini (Department of Neurological Sciences, University of Padua, School of Medicine, Padua, Italy), Andrea Salmaggi (Department of Neurology, “Alessandro Manzoni” Hospital, Lecco, Italy), Francesco Sasanelli (Neurologic Unit, Pedrabissi Hospital, Melegnano, Italy), Enrico Sasso (Neurologic Clinic, University of Parma, Italy), Luigi Specchio (Neurologic Clinic, Riuniti Hospital, University of Foggia, Foggia, Italy), Paolo Tinuper (Biomedical and Neuromotor Sciences Department, University of Bologna, Italy), Gaetano Zaccara (Neurologic Unit, S. Giovanni di Dio Hospital, Florence, Italy).

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Correspondence to Umberto Aguglia.

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This research project is financed by Italian Health Ministry (Targeted Research for Young Investigators, 2013). Project code is GR-2013-02358677. Dr. Beghi serves on the editorial advisory boards of Amyotrophic Lateral Sclerosis, Clinical Neurology and Neurosurgery, and Neuroepidemiology; he has received funding for travel and speaker honoraria from UCB-Pharma, Sanofi-Aventis, GSK, EISAI; funding from GSK for educational presentations, and from AIFA, Sanofi-Aventis, Janssen-Cilag, EISAI, Lombardy Region, Istituto Superiore di Sanità and American ALS Association for the coordinating activity of RCT and observational study protocol.

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On behalf of the Epilepsy Study Group of the Italian Neurological Society.

The members of the Epilepsy Study Group of the Italian Neurological Society are listed in acknowledgments.

S. Gasparini and E. Ferlazzo contributed equally to this work.

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Gasparini, S., Ferlazzo, E., Giussani, G. et al. Rapid versus slow withdrawal of antiepileptic monotherapy in 2-year seizure-free adult patients with epilepsy (RASLOW) study: a pragmatic multicentre, prospective, randomized, controlled study. Neurol Sci 37, 579–583 (2016). https://doi.org/10.1007/s10072-016-2483-3

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