Neurotherapeutics (Mar 2025)
First-year treatment response predicts the following 5-year disease course in patients with relapsing-remitting multiple sclerosis
- 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
Affiliations
- Simona Toscano
- Department 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, Italy
- Tim Spelman
- MSBase Foundation, VIC, Melbourne, Australia; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden
- Serkan Ozakbas
- Dokuz Eylul University, Konak, Izmir, Turkey
- Raed Alroughani
- Division of Neurology, Department of Medicine, Amiri Hospital, Sharq 73767, Kuwait
- Clara G. Chisari
- Multiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, Italy; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania 95123, Italy
- Salvatore Lo Fermo
- Multiple Sclerosis Unit, University-Hospital G. Rodolico - San Marco, Catania, Italy; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania 95123, Italy
- Alexandre Prat
- CHUM MS Center and Universite de Montreal, Montreal H2L 4M1, Canada
- Marc Girard
- CHUM MS Center and Universite de Montreal, Montreal H2L 4M1, Canada
- Pierre Duquette
- CHUM MS Center and Universite de Montreal, Montreal H2L 4M1, Canada
- Guillermo Izquierdo
- Hospital Universitario Virgen Macarena, Sevilla 41009, Spain
- Sara Eichau
- Hospital Universitario Virgen Macarena, Sevilla 41009, Spain
- Pierre Grammond
- CISSS Chaudière-Appalache, Levis G6X 0A1, Canada
- Cavit Boz
- KTU Medical Faculty Farabi Hospital, Trabzon 61080, Turkey
- Tomas Kalincik
- CORe, Department of Medicine, The University of Melbourne, Melbourne 3050, Australia; Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne 3050, Australia
- Yolanda Blanco
- Center of Neuroimmunology, Service of Neurology, Hospital Clinic de Barcelona, Barcelona, Spain
- Katherine Buzzard
- Department of Neurology, Box Hill Hospital, Melbourne 3128, Australia
- Olga Skibina
- Department of Neurology, Box Hill Hospital, Melbourne 3128, Australia
- Maria Jose Sa
- Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto 4200-319, Portugal; Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal
- Anneke van der Walt
- Department of Neurology, The Alfred Hospital, Melbourne 3000, Australia
- Helmut Butzkueven
- Department of Neurology, The Alfred Hospital, Melbourne 3000, Australia
- Murat Terzi
- Medical Faculty, 19 Mayis University, Samsun 55160, Turkey
- Oliver Gerlach
- Academic 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 Netherlands
- Francois Grand'Maison
- Neuro Rive-Sud, Quebec J4V 2J2, Canada
- Matteo Foschi
- Department 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, Italy
- Andrea Surcinelli
- Department of Neuroscience, Multiple Sclerosis Center, Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy
- Michael Barnett
- Brain and Mind Centre, Sydney 2050, Australia
- Alessandra Lugaresi
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy
- Marco Onofrj
- Department of Neuroscience, Imaging, and Clinical Sciences, University G. D'Annunzio, Chieti 66013, Italy
- Bassem Yamout
- Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
- Samia J. Khoury
- Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon
- Julie Prevost
- CSSS Saint-Jérôme, Saint-Jerome J7Z 5T3, Canada
- Jeannette Lechner-Scott
- School of Medicine and Public Health, University Newcastle, Newcastle 2305, Australia
- Davide Maimone
- Centro Sclerosi Multipla, Garibaldi Hospital, Catania 95124, Italy
- Maria Pia Amato
- Department NEUROFARBA, University of Florence, Florence 50134, Italy; IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy
- Daniele Spitaleri
- Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino 83100, Italy
- Vincent Van Pesch
- Department of Neurology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain (UCLouvain), Brussels, Belgium
- Richard Macdonell
- Austin Health, Melbourne 3084, Australia
- Elisabetta Cartechini
- AST 3 Macerata, Marche, Italy
- Koen de Gans
- Department of Neurology, Groene Hart Ziekenhuis, Gouda, Zuid-Holland, the Netherlands
- Mark Slee
- Flinders University, Adelaide 5042, Australia
- Tamara Castillo-Triviño
- Hospital Universitario Donostia and IIS Biodonostia, San Sebastián, Spain
- Aysun Soysal
- Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul 34147, Turkey
- Jose Luis Sanchez-Menoyo
- Department of Neurology, Galdakao-Usansolo University Hospital, Osakidetza-Basque Health Service, Biocruces, Spain
- Guy Laureys
- Department of Neurology, Ghent Universitary Hospital, Ghent 9000, Belgium
- Liesbeth Van Hijfte
- Department of Neurology, Ghent Universitary Hospital, Ghent 9000, Belgium
- Pamela McCombe
- Royal Brisbane and Women's Hospital, University of Queensland, Brisbane 4000, Australia
- Ayse Altintas
- Department of Neurology, School of Medicine, Koc University, Koc University Research Center for Translational Medicine (KUTTAM), Istanbul 34450, Turkey
- Bianca Weinstock-Guttman
- Department of Neurology, Buffalo General Medical Center, Buffalo 14202, United States
- Eduardo Aguera-Morales
- University Hospital Reina Sofia, Cordoba 14004, Spain
- Masoud Etemadifar
- Department of Neurosurgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
- Cristina Ramo-Tello
- Hospital Germans Trias i Pujol, Badalona 08916, Spain
- Nevin John
- Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Australia; Department of Neurology, Monash Health, Clayton, Australia
- Recai Turkoglu
- Haydarpasa Numune Training and Research Hospital, Istanbul 34668, Turkey
- Suzanne Hodgkinson
- Liverpool Hospital, Sydney 2170, Australia
- Sarah Besora
- Hospital Universitari Mútua de Terrassa, Barcelona, Spain
- Bart Van Wijmeersch
- Universitair MS Centrum, Hasselt University, Hasselt-Pelt, Belgium; Rehabilitation & MS Centre, Pelt, Belgium
- Ricardo Fernandez-Bolaños
- Department of Neurology, Hospital Universitario Virgen de Valme, Spain
- Francesco Patti
- Multiple 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.
- Journal volume & issue
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Vol. 22,
no. 2
p. e00552
Abstract
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.
