Sativex in resistant multiple sclerosis spasticity - PLOS

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Aug 1, 2017 - (CRESM)—San Luigi Gonzaga Hospital, Orbassano, Italy, 24 Multiple Sclerosis Centre—Cattolica University, ..... College Station TSL. 17.
RESEARCH ARTICLE

Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study)

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OPEN ACCESS Citation: Messina S, Solaro C, Righini I, Bergamaschi R, Bonavita S, Bossio RB, et al. (2017) Sativex in resistant multiple sclerosis spasticity: Discontinuation study in a large population of Italian patients (SA.FE. study). PLoS ONE 12(8): e0180651. https://doi.org/10.1371/ journal.pone.0180651 Editor: Orhan Aktas, Heinrich-Heine-Universitat Dusseldorf, GERMANY Received: February 6, 2017 Accepted: June 19, 2017 Published: August 1, 2017 Copyright: © 2017 Messina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Silvia Messina1☯, Claudio Solaro2, Isabella Righini3, Roberto Bergamaschi4, Simona Bonavita5, Roberto Bruno Bossio6, Vincenzo Brescia Morra7, Gianfranco Costantino8, Paola Cavalla9, Diego Centonze10,11, Giancarlo Comi12, Salvatore Cottone13, Maura Chiara Danni14, Ada Francia15, Alberto Gajofatto16, Claudio Gasperini17, Mauro Zaffaroni18, Loredana Petrucci19, Elisabetta Signoriello20, Giorgia Teresa Maniscalco21, Gabriella Spinicci22, Manuela Matta23, Massimiliano Mirabella24, Graziella Pedà25, Letizia Castelli26, Marco Rovaris27, Edoardo Sessa28, Daniele Spitaleri29, Damiano Paolicelli30, Alfredo Granata31, Mario Zappia1, Francesco Patti1☯*, on behalf of the SA.FE. study group¶ 1 Department of Medical, Surgical Science and Advanced Technology "GF Ingrassia"–University of Catania, Catania, Italy, 2 Neurology Unit, Department Head And Neck, ASL3 Genova, Italy, 3 Department NEUROFARBA—University of Florence, Florence, Italy, 4 Department of Neurology—Neurology Institute C Mondino, Pavia, Italy, 5 I clinic Neurology—II University of Naples, Naples, Italy, 6 Neurology Operating Unit and Multiple Sclerosis Center—Provincial Health Authority of Cosenza, Cosenza, Italy, 7 Multiple Sclerosis Centre— University Federico II, Naples, Italy, 8 Demyelinating Diseases Centre—Foggia Hospital, Foggia, Italy, 9 A.O.U: Cittàdella Salute e dellaScienza di Torino, Torino, Italy, 10 Neuroscience Department—University Tor Vegata, Rome, Italy, 11 Unit of Neurology and of Neurorehabilitation, IRCCS Neuromed, Pozzilli (IS), Italy, 12 Department of Neurology–San Raffaele Hospital, Milan, Italy, 13 Neuroimmunology Unit—Villa SofiaCervello Hospital, Palermo, Italy, 14 Neurology Clinic—Ancona Hospital, Ancona, Italy, 15 Multiple Sclerosis Center, Dept. Neurol. Psich—Sapienza University, Rome, Italy, 16 Department of Neuroscience, Biomedicine and Movement Multiple Sclerosis Centre–University of Verona, Verona, Italy, 17 Neurology Division—San Camillo Hospital, Rome, Italy, 18 Multiple Sclerosis Centre—Sant’Antonio Abate Hospital, Gallarate, Italy, 19 Multiple Sclerosis Centre—University Hospital Pisa, Pisa, Italy, 20 Multiple Sclerosis Center—Second University of Naples, Naples, Italy, 21 Multiple Sclerosis Centre—Cardarelli Hospital, Naples, Italy, 22 Department of Medical Sciences—University of Cagliari, Cagliari, Italy, 23 Multiple Sclerosis Centre (CRESM)—San Luigi Gonzaga Hospital, Orbassano, Italy, 24 Multiple Sclerosis Centre—Cattolica University, Rome, Italy, 25 Multiple Sclerosis Centre—Vaio Hospital, Fidenza, Italy, 26 Multiple Sclerosis Centre—S. Andrea Hospital, Rome, Italy, 27 Multiple Sclerosis Centre—IRCCS Don Gnocchi Foundation, Milan, Italy, 28 Multiple Sclerosis Centre—IRCCS-Bonino Pulejo Centre, Messina, Italy, 29 Multiple Sclerosis Centre—San G. Moscati Hospital, Avellino, Italy, 30 Department of Basic Medical Sciences, Neuroscience and Sense Organs —University of Bari “Aldo Moro” Bari, Italy, 31 Department of Medical Sciences, Institute of Neurology— University “Magna Graecia”, Catanzaro, Italy ☯ These authors contributed equally to this work. ¶ The complete membership of the author group can be found in the Acknowledgments. * [email protected]

Data Availability Statement: All relevant data are within the paper and its Supporting Information files.

Abstract

Funding: The authors received no specific funding for this work.

Background

Competing interests: Dr Messina has received honoraria for scientific lectures form Biogen, Almirall, travel payment from Novartis, Biogen Idec, Genzyme, Almirall Bayer Schering, Merck Serono, Teva, and she serves on a scientific

The approval of Sativex for the management of multiple sclerosis (MS) spasticity opened a new opportunity to many patients. In Italy, the healthcare payer can be fully reimbursed by the involved pharma company with the cost of treatment for patients not responding after a 4 week (28 days) trial period (Payment by Results, PbR), and 50% reimbursed with the cost of 6 weeks (42 days) treatment for other patients discontinuing (Cost Sharing, CS). The aim

PLOS ONE | https://doi.org/10.1371/journal.pone.0180651 August 1, 2017

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Sativex in resistant MS spasticity

advisory board for Biogen. Dr Solaro received honoraria from Biogen, Genzyme, Novartis, Merck Serono, Almirall, Teva. Dr Righini has nothing to disclose. Dr Bergamaschi has received honoraria for scientific lectures and travel payment from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Prof Bonavita received speaker and advisory board honoraria from Biogen, Novartis and Merck-Serono. Dr Bruno Bossio received a grant for advisory board activities from Almirall. Dr Brescia Morra has received honoraria for scientific lectures and travel payment from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Dr Costantino reveived honoraria for speaking activities from Genzyme, Merck-Serono, Biogen and Novartis. Dr Cavalla has nothing to disclose. Prof DiegoCentonze is an Advisory Board member of Almirall, Bayer Schering, Biogen, Genzyme, GW Pharmaceuticals, Merck-Serono, Novartis, Teva and received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen Idec, Genzyme, GW Pharmaceuticals, Merck Serono, Novartis, Sanofi-Aventis, Teva. He is also an external expert consultant of the European Medicine Agency (EMA), and the principal investigator in clinical trials for Bayer Schering, Biogen Idec, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-aventis, Teva. His preclinical and clinical research was supported by grants from Bayer, Biogen, MerckSerono, Novartis e Teva. Prof Comi has received honoraria for scientific lectures from Biogen, Novartis, Teva, Genzyme, Bayer Schering, Merck Serono, Almirall. Dr Cottone has received honoraria for advisory board activity from Bayer Schering. Prof Danni has received honoraria for scientific lectures from Novartis, Merck-Serono, Biogen, Teva. Dr Francia received a grant for advisory board activities from Almirall. Dr Gajofatto has received support for travel to scientific meetings from Almirall, Biogen, Genzyme, MerckSerono and Novartis. Dr Gasperini received honoraria from Biogen, Genzyme, Novartis, Merck Serono, Almirall, Teva. Dr Zaffaroni received honoraria from Biogen, Genzyme, Novartis, Merck Serono, Almirall, Teva. Dr Petrucci has nothing to disclose. Dr Signoriello has nothing to disclose. Dr Maniscalco received speaking and advisory honoraria from Biogen, Novartis and Teva. Dr Spinicci has nothing to disclose. Dr. Matta received honoraria for serving in the scientific advisory boards of Almirall, Novartis, Biogen, Genzyme. Dr Mirabella received honoraria from Biogen, Genzyme, Novartis, Merck Serono, Almirall, Teva. Dr Pedà has nothing to disclose. Dr Castelli has nothing to disclose. Dr Rovaris received honoraria from Biogen, Genzyme, Novartis, Merck Serono,

of our study was to describe the Sativex discontinuation profile from a large population of spasticity treated Italian MS patients.

Methods We collected data of patients from 30 MS centres across the country starting Sativex between January 2014 and February 2015. Data were collected from the mandatory Italian Medicines Agency (AIFA) web-registry. Predictors of treatment discontinuation were assessed using a multivariate Cox proportional regression analysis.

Results During the observation period 631 out of 1597 (39.5%) patients discontinued Sativex. The Kaplan-Meier estimates curve showed that 333 patients (20.8%) discontinued treatment at 4 weeks while 422 patients (26.4%) discontinued at 6 weeks. We found after adjusted modeling that a higher NRS score at T1 (adjHR 2.23, 95% 2.07–2.41, p