Pietro Iaffaldano1, Giuseppe Lucisano2, Francesco Patti3, Vincenzo Brescia Morra4, Giovanna De Luca5, Alessandra Lugaresi6, Mauro Zaffaroni7, Matilde Inglese8, Giuseppe Salemi9, Eleonora Cocco10, Antonella Conte11, Diana Ferraro12, Simonetta Galgani13, Roberto Bergamaschi14, Carlo Pozzilli15, Marco Salvetti16, Giacomo Lus17, Marco Rovaris18, Giorgia Teresa Maniscalco19, Francesco Ottavio Logullo20, Damiano Paolicelli1, Mariaclara Achille1, Giuseppina Marrazzo21, Valeria Lovato21, Giancarlo Comi22, Massimo Filippi22, Maria Pia Amato23, Maria Trojano1. 1. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy. 2. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro," Bari, Italy/Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy. 3. Dipartimento di Scienze Mediche e Chirurgiche e Tecnologie Avanzate, GF Ingrassia, Sez. Neuroscienze, Centro Sclerosi Multipla, Università di Catania, Catania, Italy. 4. Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience (NSRO), Federico II University, Naples, Italy. 5. Centro Sclerosi Multipla, Clinica Neurologica, Policlinico SS Annunziata, Università G. D'Annunzio, Chieti, Italy. 6. IRCCS Istituto delle Scienze Neurologiche di Bologna, Riabilitazione Sclerosi Multipla, Bologna, Italy/Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy. 7. Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate, Italy. 8. Dipartimento Di Neuroscienze, Riabilitazione, Oftalmologia, Genetica E Scienze Materno-Infantili (DINOGMI), Genova, Italy/Ospedale Policlinico San Martino, IRCCS, Genova, Italy. 9. Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy. 10. Department Medical Science and Public health, University of Cagliari/ Centro Sclerosi Multipla, ATS Sardegna, Cagliari, Italy. 11. Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy/IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy. 12. Department of Neurosciences, Neurology Unit, University of Modena and Reggio Emilia, Nuovo Ospedale Civile S. Agostino/Estense, Modena, Italy. 13. Centro Sclerosi Multipla-Azienda Ospedaliera S. Camillo Forlanini, Rome, Italy. 14. IRCCS Mondino Foundation, Pavia, Italy. 15. Multiple Sclerosis Center, S.Andrea Hospital, Dept. of Human Neuroscience, Sapienza University, Rome, Italy. 16. IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy/CENTERS Centro Neurologico Terapie Sperimentali-Sapienza University, S.Andrea Hospital, Rome, Italy. 17. Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Caserta, Italy. 18. Multiple Sclerosis Center, IRCCS Fondazione don Carlo Gnocchi ONLUS, Milan, Italy. 19. Centro regionale SM Ospedale A. Cardarelli, Napoli, Italy. 20. UOC Neurologia Macerata Area Vasta 3, Asur Marche, Macerata, Italy. 21. Roche SpA, Monza, Italy. 22. Department of Neurology, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy. 23. Department of Neurofarba, University of Florence, Florence, Italy/IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
Abstract
BACKGROUND: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. OBJECTIVE: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). METHODS: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. RESULTS: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. CONCLUSION: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
BACKGROUND: No uniform criteria for a sensitive identification of the transition from relapsing-remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available. OBJECTIVE: To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA). METHODS: Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models. RESULTS: SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0. CONCLUSION: A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
Authors: Corey C Ford; Jeffrey A Cohen; Andrew D Goodman; John W Lindsey; Robert P Lisak; Christopher Luzzio; Amy Pruitt; John Rose; Horea Rus; Jerry S Wolinsky; Shaul E Kadosh; Emily Bernstein-Hanlon; Yafit Stark; Jessica K Alexander Journal: Mult Scler Date: 2022-06-29 Impact factor: 5.855