Defining the risk factors for the conversion to secondary progressive multiple sclerosis: a retrospective cohort study of the Italian MS Register
ECTRIMS Online Library. Iaffaldano P. 09/12/19; 279454; 156
Pietro Iaffaldano
Pietro Iaffaldano
Contributions
Abstract

Abstract: 156

Type: Scientific Session

Abstract Category: Clinical aspects of MS - Progressive MS

P. Iaffaldano1, G. Lucisano2, F. Patti3, V. Brescia Morra4, G. De Luca5, A. Lugaresi6,7, M. Zaffaroni8, M. Inglese9,10, G. Salemi11, E. Cocco12, E. Millefiorini13, P. Sola14, S. Calgani15, R. Bergamaschi16, C. Pozzilli17, M. Salvetti18,19, G. Lus20, M. Rovaris21, G.T. Maniscalco22, F.O. Logullo23, D. Paolicelli1, M. Achille1, M. Aiello24, V. Lovato24, G. Comi25, M.P. Amato26, M. Trojano1, on behalf of the Italian MS Register

1Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, 2Center for Outcomes Research and Clinical Epidemiology, Pescara, 3Dipartimento di Scienze Mediche e Chirurgiche e Tecnologie Avanzate, GF Ingrassia, Sez. Neuroscienze, Centro Sclerosi Multipla, Università di Catania, Catania, 4Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, 5Clinica Neurologica, Universita' G. D'Annunzio, Chieti, 6IRCCS Istituto delle Scienze Neurologiche di Bologna, 7Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, 8Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate (Varese), 9Dipartimento Di Neuroscienze, Riabilitazione, Oftalmologia, Genetica E Scienze Materno - Infantili (DINOGMI), Universita' di Genova, 10Ospedale Policlinico San Martino, IRCCS, Genova, 11Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, 12Department Medical Science and Public Health, Centro Sclerosi Multipla, University of Cagliari, Cagliari, 13Multiple Sclerosis Center, Policlinico Umberto I, Sapienza University, Rome, 14Department of Neurosciences, Neurology Unit, Nuovo Ospedale Civile S. Agostino/Estense, University of Modena and Reggio Emilia, Modena, 15Centro Sclerosi Multipla - Azienda Ospedaliera S. Camillo Forlanini, Rome, 16IRCCS Mondino Foundation, Pavia, 17Multiple Sclerosis Center, S.Andrea Hospital, Department of Human Neuroscience, 18CENTERS Centro Neurologico Terapie Sperimentali - Azienda Ospedaliera S. Andrea, Sapienza University, Rome, 19IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, 20Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, 21Multiple Sclerosis Center, IRCCS Fondazione don Carlo Gnocchi ONLUS, Milan, 22Neurological Clinic and Multiple Sclerosis Center, A Cardarelli Hospital, Naples, 23Centro Sclerosi Multipla - UOC Neurologia - Ospedale di Macerata, Macerata, 24Roche S.p.A., Monza, 25Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, 26Department of NEUROFARBA, University of Florence, Florence, Italy

Background: No clear metrics for sensitive and reliable identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive (SP)MS are available.
Objectives: to evaluate the prevalence of, and the risk factors for, the conversion to SPMS in a cohort of RRMS patients extracted from the Italian MS Registry using two different definitions of SPMS.
Methods: patients with ≥5 years follow-up, and ≥3 EDSS score evaluations were selected from the Italian MS Registry.Two definitions of SPMS were applied: firstly, the date of conversion to SP annotated in the database, which was based on the subjective judgement of the neurologists, was extracted; secondly, a data driven definition, based on an EDSS increase with at least 3-month apart confirmation in the absence of a relapse, a minimum EDSS step ≥4 and pyramidal score ≥2, was applied. The risk of reaching the SPMS was assessed by using multivariate Cox proportional hazards models.
Results: a cohort of 19,318 RRMS patients was included in the analysis. A total of 3,868 (20.0%) patients were classified as SP by the neurologist' judgement.
By applying our algorithm definition 2,343 (12.1%) patients were classified as SP.
Based on the neurologist' definition the median (IQR) time to conversion to SP was 12.0(7.0-18.7) years, the mean age at SP was 44.3(10.1) years and the median EDSS score at the time of conversion was 4.5(4.0 - 6.0), ranging from 0 to 9.0.
By applying the algorithm definition, the median time to conversion to SPMS was 14.4(9.9-22.5) years, the median age at SP was 47.2(40.2-54.9) years and the median EDSS score at the time of conversion was 4.5(4.0-6.0), ranging from 4 to 9.0.
Both the multivariate models showed that an age at onset >40 years, a multifocal onset, a higher baseline EDSS score and a higher number of relapses during the RR phase were all significant risk factors for the conversion to SP. Female sex, a longer duration of the RR phase and a longer exposure to disease modifying therapies (DMTs) were all protective factors against the transition to the SP. Only for the neurologist' definition a shorter time from disease onset to the first DMT start was associated to a reduced risk of conversion to SP.
Conclusions: Real-world data from the Italian MS Registry suggests that a timely and continuous DMTs exposure reduces the risk of conversion from RR to SPMS.
Disclosure: This project was supported by Roche S.p.A., Monza, Italyon the basis of a Sponsored Research Agreement in place with the University of Bari Aldo Moro.
MA and VL are employees of Roche S.p.A., Monza, Italy.
All the authors report no competing interest related to this specific project.
The authors report no conflicts of interest with respect to the contents of the current study, but note that the patients in the study were treated with a number of disease modifying drugs and that authors PI, FP, VBM, GDL, AL, MZ, MI, GS, EL, EM, PS, SG, RB, CP, MS, GL, MR, GTM, FOL, DP, GC, MPA, and MT report have received advisory board membership, speakers honoraria, travel support, research grants, consulting fees, or clinical trial support from the manufacturers of those drugs, including Actelion, Allergan, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Forward Pharma, Ipsen, Medday, Merck, Merz, Mylan, Novartis, Sanofi, Roche, Teva, and their local affiliates.
GL, MA have nothing to disclose.

Abstract: 156

Type: Scientific Session

Abstract Category: Clinical aspects of MS - Progressive MS

P. Iaffaldano1, G. Lucisano2, F. Patti3, V. Brescia Morra4, G. De Luca5, A. Lugaresi6,7, M. Zaffaroni8, M. Inglese9,10, G. Salemi11, E. Cocco12, E. Millefiorini13, P. Sola14, S. Calgani15, R. Bergamaschi16, C. Pozzilli17, M. Salvetti18,19, G. Lus20, M. Rovaris21, G.T. Maniscalco22, F.O. Logullo23, D. Paolicelli1, M. Achille1, M. Aiello24, V. Lovato24, G. Comi25, M.P. Amato26, M. Trojano1, on behalf of the Italian MS Register

1Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, 2Center for Outcomes Research and Clinical Epidemiology, Pescara, 3Dipartimento di Scienze Mediche e Chirurgiche e Tecnologie Avanzate, GF Ingrassia, Sez. Neuroscienze, Centro Sclerosi Multipla, Università di Catania, Catania, 4Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, 5Clinica Neurologica, Universita' G. D'Annunzio, Chieti, 6IRCCS Istituto delle Scienze Neurologiche di Bologna, 7Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, 8Multiple Sclerosis Center, S.Antonio Abate Hospital, Gallarate (Varese), 9Dipartimento Di Neuroscienze, Riabilitazione, Oftalmologia, Genetica E Scienze Materno - Infantili (DINOGMI), Universita' di Genova, 10Ospedale Policlinico San Martino, IRCCS, Genova, 11Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, 12Department Medical Science and Public Health, Centro Sclerosi Multipla, University of Cagliari, Cagliari, 13Multiple Sclerosis Center, Policlinico Umberto I, Sapienza University, Rome, 14Department of Neurosciences, Neurology Unit, Nuovo Ospedale Civile S. Agostino/Estense, University of Modena and Reggio Emilia, Modena, 15Centro Sclerosi Multipla - Azienda Ospedaliera S. Camillo Forlanini, Rome, 16IRCCS Mondino Foundation, Pavia, 17Multiple Sclerosis Center, S.Andrea Hospital, Department of Human Neuroscience, 18CENTERS Centro Neurologico Terapie Sperimentali - Azienda Ospedaliera S. Andrea, Sapienza University, Rome, 19IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, 20Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, 21Multiple Sclerosis Center, IRCCS Fondazione don Carlo Gnocchi ONLUS, Milan, 22Neurological Clinic and Multiple Sclerosis Center, A Cardarelli Hospital, Naples, 23Centro Sclerosi Multipla - UOC Neurologia - Ospedale di Macerata, Macerata, 24Roche S.p.A., Monza, 25Department of Neurology, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, 26Department of NEUROFARBA, University of Florence, Florence, Italy

Background: No clear metrics for sensitive and reliable identification of the transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive (SP)MS are available.
Objectives: to evaluate the prevalence of, and the risk factors for, the conversion to SPMS in a cohort of RRMS patients extracted from the Italian MS Registry using two different definitions of SPMS.
Methods: patients with ≥5 years follow-up, and ≥3 EDSS score evaluations were selected from the Italian MS Registry.Two definitions of SPMS were applied: firstly, the date of conversion to SP annotated in the database, which was based on the subjective judgement of the neurologists, was extracted; secondly, a data driven definition, based on an EDSS increase with at least 3-month apart confirmation in the absence of a relapse, a minimum EDSS step ≥4 and pyramidal score ≥2, was applied. The risk of reaching the SPMS was assessed by using multivariate Cox proportional hazards models.
Results: a cohort of 19,318 RRMS patients was included in the analysis. A total of 3,868 (20.0%) patients were classified as SP by the neurologist' judgement.
By applying our algorithm definition 2,343 (12.1%) patients were classified as SP.
Based on the neurologist' definition the median (IQR) time to conversion to SP was 12.0(7.0-18.7) years, the mean age at SP was 44.3(10.1) years and the median EDSS score at the time of conversion was 4.5(4.0 - 6.0), ranging from 0 to 9.0.
By applying the algorithm definition, the median time to conversion to SPMS was 14.4(9.9-22.5) years, the median age at SP was 47.2(40.2-54.9) years and the median EDSS score at the time of conversion was 4.5(4.0-6.0), ranging from 4 to 9.0.
Both the multivariate models showed that an age at onset >40 years, a multifocal onset, a higher baseline EDSS score and a higher number of relapses during the RR phase were all significant risk factors for the conversion to SP. Female sex, a longer duration of the RR phase and a longer exposure to disease modifying therapies (DMTs) were all protective factors against the transition to the SP. Only for the neurologist' definition a shorter time from disease onset to the first DMT start was associated to a reduced risk of conversion to SP.
Conclusions: Real-world data from the Italian MS Registry suggests that a timely and continuous DMTs exposure reduces the risk of conversion from RR to SPMS.
Disclosure: This project was supported by Roche S.p.A., Monza, Italyon the basis of a Sponsored Research Agreement in place with the University of Bari Aldo Moro.
MA and VL are employees of Roche S.p.A., Monza, Italy.
All the authors report no competing interest related to this specific project.
The authors report no conflicts of interest with respect to the contents of the current study, but note that the patients in the study were treated with a number of disease modifying drugs and that authors PI, FP, VBM, GDL, AL, MZ, MI, GS, EL, EM, PS, SG, RB, CP, MS, GL, MR, GTM, FOL, DP, GC, MPA, and MT report have received advisory board membership, speakers honoraria, travel support, research grants, consulting fees, or clinical trial support from the manufacturers of those drugs, including Actelion, Allergan, Almirall, Bayer Schering, Biogen, Celgene, Excemed, Genzyme, Forward Pharma, Ipsen, Medday, Merck, Merz, Mylan, Novartis, Sanofi, Roche, Teva, and their local affiliates.
GL, MA have nothing to disclose.

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