First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis

Predicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsin...

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Main Authors: Simona Toscano, Tim Spelman, Serkan Ozakbas, Raed Alroughani, Clara G. Chisari, Salvatore Lo Fermo, Alexandre Prat, Marc Girard, Pierre Duquette, Guillermo Izquierdo, Sara Eichau, Pierre Grammond, Cavit Boz, Tomas Kalincik, Yolanda Blanco, Katherine Buzzard, Olga Skibina, Maria Jose Sa, Anneke van der Walt, Helmut Butzkueven, Murat Terzi, Oliver Gerlach, Francois Grand'Maison, Matteo Foschi, Andrea Surcinelli, Michael Barnett, Alessandra Lugaresi, Marco Onofrj, Bassem Yamout, Samia J. Khoury, Julie Prevost, Jeannette Lechner-Scott, Davide Maimone, Maria Pia Amato, Daniele Spitaleri, Vincent Van Pesch, Richard Macdonell, Elisabetta Cartechini, Koen de Gans, Mark Slee, Tamara Castillo-Triviño, Aysun Soysal, Jose Luis Sanchez-Menoyo, Guy Laureys, Liesbeth Van Hijfte, Pamela McCombe, Ayse Altintas, Bianca Weinstock-Guttman, Eduardo Aguera-Morales, Masoud Etemadifar, Cristina Ramo-Tello, Nevin John, Recai Turkoglu, Suzanne Hodgkinson, Sarah Besora, Bart Van Wijmeersch, Ricardo Fernandez-Bolaños, Francesco Patti
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Neurotherapeutics
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Online Access:http://www.sciencedirect.com/science/article/pii/S1878747925000303
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author Simona Toscano
Tim Spelman
Serkan Ozakbas
Raed Alroughani
Clara G. Chisari
Salvatore Lo Fermo
Alexandre Prat
Marc Girard
Pierre Duquette
Guillermo Izquierdo
Sara Eichau
Pierre Grammond
Cavit Boz
Tomas Kalincik
Yolanda Blanco
Katherine Buzzard
Olga Skibina
Maria Jose Sa
Anneke van der Walt
Helmut Butzkueven
Murat Terzi
Oliver Gerlach
Francois Grand'Maison
Matteo Foschi
Andrea Surcinelli
Michael Barnett
Alessandra Lugaresi
Marco Onofrj
Bassem Yamout
Samia J. Khoury
Julie Prevost
Jeannette Lechner-Scott
Davide Maimone
Maria Pia Amato
Daniele Spitaleri
Vincent Van Pesch
Richard Macdonell
Elisabetta Cartechini
Koen de Gans
Mark Slee
Tamara Castillo-Triviño
Aysun Soysal
Jose Luis Sanchez-Menoyo
Guy Laureys
Liesbeth Van Hijfte
Pamela McCombe
Ayse Altintas
Bianca Weinstock-Guttman
Eduardo Aguera-Morales
Masoud Etemadifar
Cristina Ramo-Tello
Nevin John
Recai Turkoglu
Suzanne Hodgkinson
Sarah Besora
Bart Van Wijmeersch
Ricardo Fernandez-Bolaños
Francesco Patti
author_facet Simona Toscano
Tim Spelman
Serkan Ozakbas
Raed Alroughani
Clara G. Chisari
Salvatore Lo Fermo
Alexandre Prat
Marc Girard
Pierre Duquette
Guillermo Izquierdo
Sara Eichau
Pierre Grammond
Cavit Boz
Tomas Kalincik
Yolanda Blanco
Katherine Buzzard
Olga Skibina
Maria Jose Sa
Anneke van der Walt
Helmut Butzkueven
Murat Terzi
Oliver Gerlach
Francois Grand'Maison
Matteo Foschi
Andrea Surcinelli
Michael Barnett
Alessandra Lugaresi
Marco Onofrj
Bassem Yamout
Samia J. Khoury
Julie Prevost
Jeannette Lechner-Scott
Davide Maimone
Maria Pia Amato
Daniele Spitaleri
Vincent Van Pesch
Richard Macdonell
Elisabetta Cartechini
Koen de Gans
Mark Slee
Tamara Castillo-Triviño
Aysun Soysal
Jose Luis Sanchez-Menoyo
Guy Laureys
Liesbeth Van Hijfte
Pamela McCombe
Ayse Altintas
Bianca Weinstock-Guttman
Eduardo Aguera-Morales
Masoud Etemadifar
Cristina Ramo-Tello
Nevin John
Recai Turkoglu
Suzanne Hodgkinson
Sarah Besora
Bart Van Wijmeersch
Ricardo Fernandez-Bolaños
Francesco Patti
author_sort Simona Toscano
collection DOAJ
description Predicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsing-remitting MS (RRMS). We recruited patients from MSBase Registry covering the period between 1996 and 2022. All patients were diagnosed with RRMS and actively followed-up for at least 5 years to explore the following outcomes: clinical relapses, confirmed disability worsening (CDW) and improvement (CDI), EDSS 3.0, EDSS 6.0, conversion to secondary progressive MS (SPMS), new MRI lesions, Progression Independent of Relapse Activity (PIRA). Predictors included demographic, clinical and radiological data, and sub-optimal response (SR) within the first year of treatment. Female sex (HR 1.27; 95 ​% CI 1.16–1.40) and EDSS at baseline (HR 1.19; 95 ​% CI 1.15–1.24) were independent risk factors for the occurrence of relapses during the first 5 years after diagnosis, while high-efficacy treatment (HR 0.78; 95 ​% CI 0.67–0.91) and age at diagnosis (HR 0.83; 95 ​% CI 0.79–0.86) significantly reduced the risk. SR predicted clinical relapses (HR ​= ​3.84; 95 ​% CI 3.51–4.19), CDW (HR ​= ​1.74; 95 ​% CI 1.56–1.93), EDSS 3.0 (HR ​= ​3.01; 95 ​% CI 2.58–3.51), EDSS 6.0 (HR ​= ​1.77; 95 ​% CI 1.43–2.20) and new brain (HR ​= ​2.33; 95 ​% CI 2.04–2.66) and spinal (HR 1.65; 95 ​% CI 1.29–2.09) MRI lesions. This study highlights the importance of selecting the appropriate DMT for each patient soon after MS diagnosis, also providing clinicians with a practical tool able to calculate personalized risk estimates for different outcomes.
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spelling doaj-art-855bb5f1ff16447c94e70232e554a1d32025-08-20T02:18:00ZengElsevierNeurotherapeutics1878-74792025-03-01222e0055210.1016/j.neurot.2025.e00552First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosisSimona Toscano0Tim Spelman1Serkan Ozakbas2Raed Alroughani3Clara G. Chisari4Salvatore Lo Fermo5Alexandre Prat6Marc Girard7Pierre Duquette8Guillermo Izquierdo9Sara Eichau10Pierre Grammond11Cavit Boz12Tomas Kalincik13Yolanda Blanco14Katherine Buzzard15Olga Skibina16Maria Jose Sa17Anneke van der Walt18Helmut Butzkueven19Murat Terzi20Oliver Gerlach21Francois Grand'Maison22Matteo Foschi23Andrea Surcinelli24Michael Barnett25Alessandra Lugaresi26Marco Onofrj27Bassem Yamout28Samia J. Khoury29Julie Prevost30Jeannette Lechner-Scott31Davide Maimone32Maria Pia Amato33Daniele Spitaleri34Vincent Van Pesch35Richard Macdonell36Elisabetta Cartechini37Koen de Gans38Mark Slee39Tamara Castillo-Triviño40Aysun Soysal41Jose Luis Sanchez-Menoyo42Guy Laureys43Liesbeth Van Hijfte44Pamela McCombe45Ayse Altintas46Bianca Weinstock-Guttman47Eduardo Aguera-Morales48Masoud Etemadifar49Cristina Ramo-Tello50Nevin John51Recai Turkoglu52Suzanne Hodgkinson53Sarah Besora54Bart Van Wijmeersch55Ricardo Fernandez-Bolaños56Francesco Patti57Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; Multiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, ItalyMSBase Foundation, VIC, Melbourne, Australia; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, SwedenDokuz Eylul University, Konak, Izmir, TurkeyDivision of Neurology, Department of Medicine, Amiri Hospital, Sharq 73767, KuwaitMultiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, Italy; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania 95123, ItalyMultiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, Italy; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania 95123, ItalyCHUM MS Center and Universite de Montreal, Montreal H2L 4M1, CanadaCHUM MS Center and Universite de Montreal, Montreal H2L 4M1, CanadaCHUM MS Center and Universite de Montreal, Montreal H2L 4M1, CanadaHospital Universitario Virgen Macarena, Sevilla 41009, SpainHospital Universitario Virgen Macarena, Sevilla 41009, SpainCISSS Chaudière-Appalache, Levis G6X 0A1, CanadaKTU Medical Faculty Farabi Hospital, Trabzon 61080, TurkeyCORe, Department of Medicine, The University of Melbourne, Melbourne 3050, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne 3050, AustraliaCenter of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, SpainDepartment of Neurology, Box Hill Hospital, Melbourne 3128, AustraliaDepartment of Neurology, Box Hill Hospital, Melbourne 3128, AustraliaDepartment of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto 4200-319, Portugal; Faculty of Health Sciences, University Fernando Pessoa, Porto, PortugalDepartment of Neurology, The Alfred Hospital, Melbourne 3000, AustraliaDepartment of Neurology, The Alfred Hospital, Melbourne 3000, AustraliaMedical Faculty, 19 Mayis University, Samsun 55160, TurkeyAcademic MS Center Zuyd, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen 5500, the Netherlands; School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Center, Maastricht 6131 BK, the NetherlandsNeuro Rive-Sud, Quebec J4V 2J2, CanadaDepartment of Neuroscience, Multiple Sclerosis Center, Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy; Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, ItalyDepartment of Neuroscience, Multiple Sclerosis Center, Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, ItalyBrain and Mind Centre, Sydney 2050, AustraliaIRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, ItalyDepartment of Neuroscience, Imaging, and Clinical Sciences, University G. D'Annunzio, Chieti 66013, ItalyNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut 1107 2020, LebanonNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut 1107 2020, LebanonCSSS Saint-Jérôme, Saint-Jerome J7Z 5T3, CanadaSchool of Medicine and Public Health, University Newcastle, Newcastle 2305, AustraliaCentro Sclerosi Multipla, Garibaldi Hospital, Catania 95124, ItalyDepartment NEUROFARBA, University of Florence, Florence 50134, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, ItalyAzienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino 83100, ItalyDepartment of Neurology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, BelgiumAustin Health, Melbourne 3084, AustraliaAST 3 Macerata, Marche, ItalyDepartment of Neurology, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, the NetherlandsFlinders University, Adelaide 5042, AustraliaHospital Universitario Donostia and IIS Biodonostia, San Sebastián, SpainBakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul 34147, TurkeyDepartment of Neurology, Galdakao-Usansolo University Hospital, Osakidetza-Basque Health Service, Biocruces, SpainDepartment of Neurology, Ghent Universitary Hospital, Ghent 9000, BelgiumDepartment of Neurology, Ghent Universitary Hospital, Ghent 9000, BelgiumRoyal Brisbane and Women's Hospital, University of Queensland, Brisbane 4000, AustraliaDepartment of Neurology, School of Medicine, Koc University, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul 34450, TurkeyDepartment of Neurology, Buffalo General Medical Center, Buffalo 14202, United StatesUniversity Hospital Reina Sofia, Cordoba 14004, SpainDepartment of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, IranHospital Germans Trias i Pujol, Badalona 08916, SpainDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia; Department of Neurology, Monash Health, Clayton, AustraliaHaydarpasa Numune Training and Research Hospital, Istanbul 34668, TurkeyLiverpool Hospital, Sydney 2170, AustraliaHospital Universitari Mútua de Terrassa, Barcelona, SpainUniversitair MS Centrum, Hasselt University, Hasselt-Pelt, Belgium; Rehabilitation & MS Centre, Pelt, BelgiumDepartment of Neurology, Hospital Universitario Virgen de Valme, SpainMultiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, Italy; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania 95123, Italy; Corresponding author.Predicting long-term prognosis and choosing the appropriate therapeutic approach in patients with Multiple Sclerosis (MS) at the time of diagnosis is crucial in view of a personalized medicine. We investigated the impact of early therapeutic response on the 5-year prognosis of patients with relapsing-remitting MS (RRMS). We recruited patients from MSBase Registry covering the period between 1996 and 2022. All patients were diagnosed with RRMS and actively followed-up for at least 5 years to explore the following outcomes: clinical relapses, confirmed disability worsening (CDW) and improvement (CDI), EDSS 3.0, EDSS 6.0, conversion to secondary progressive MS (SPMS), new MRI lesions, Progression Independent of Relapse Activity (PIRA). Predictors included demographic, clinical and radiological data, and sub-optimal response (SR) within the first year of treatment. Female sex (HR 1.27; 95 ​% CI 1.16–1.40) and EDSS at baseline (HR 1.19; 95 ​% CI 1.15–1.24) were independent risk factors for the occurrence of relapses during the first 5 years after diagnosis, while high-efficacy treatment (HR 0.78; 95 ​% CI 0.67–0.91) and age at diagnosis (HR 0.83; 95 ​% CI 0.79–0.86) significantly reduced the risk. SR predicted clinical relapses (HR ​= ​3.84; 95 ​% CI 3.51–4.19), CDW (HR ​= ​1.74; 95 ​% CI 1.56–1.93), EDSS 3.0 (HR ​= ​3.01; 95 ​% CI 2.58–3.51), EDSS 6.0 (HR ​= ​1.77; 95 ​% CI 1.43–2.20) and new brain (HR ​= ​2.33; 95 ​% CI 2.04–2.66) and spinal (HR 1.65; 95 ​% CI 1.29–2.09) MRI lesions. This study highlights the importance of selecting the appropriate DMT for each patient soon after MS diagnosis, also providing clinicians with a practical tool able to calculate personalized risk estimates for different outcomes.http://www.sciencedirect.com/science/article/pii/S1878747925000303Multiple sclerosisDisease-modifying treatmentPrognosisNomogramHigh-efficacy drugs
spellingShingle Simona Toscano
Tim Spelman
Serkan Ozakbas
Raed Alroughani
Clara G. Chisari
Salvatore Lo Fermo
Alexandre Prat
Marc Girard
Pierre Duquette
Guillermo Izquierdo
Sara Eichau
Pierre Grammond
Cavit Boz
Tomas Kalincik
Yolanda Blanco
Katherine Buzzard
Olga Skibina
Maria Jose Sa
Anneke van der Walt
Helmut Butzkueven
Murat Terzi
Oliver Gerlach
Francois Grand'Maison
Matteo Foschi
Andrea Surcinelli
Michael Barnett
Alessandra Lugaresi
Marco Onofrj
Bassem Yamout
Samia J. Khoury
Julie Prevost
Jeannette Lechner-Scott
Davide Maimone
Maria Pia Amato
Daniele Spitaleri
Vincent Van Pesch
Richard Macdonell
Elisabetta Cartechini
Koen de Gans
Mark Slee
Tamara Castillo-Triviño
Aysun Soysal
Jose Luis Sanchez-Menoyo
Guy Laureys
Liesbeth Van Hijfte
Pamela McCombe
Ayse Altintas
Bianca Weinstock-Guttman
Eduardo Aguera-Morales
Masoud Etemadifar
Cristina Ramo-Tello
Nevin John
Recai Turkoglu
Suzanne Hodgkinson
Sarah Besora
Bart Van Wijmeersch
Ricardo Fernandez-Bolaños
Francesco Patti
First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
Neurotherapeutics
Multiple sclerosis
Disease-modifying treatment
Prognosis
Nomogram
High-efficacy drugs
title First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
title_full First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
title_fullStr First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
title_full_unstemmed First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
title_short First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
title_sort first year treatment response predicts the following 5 year disease course in patients with relapsing remitting multiple sclerosis
topic Multiple sclerosis
Disease-modifying treatment
Prognosis
Nomogram
High-efficacy drugs
url http://www.sciencedirect.com/science/article/pii/S1878747925000303
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