title: Long-term disability trajectories in primary progressive MS patients: A latent class growth analysis.
abstract: Several natural history studies on primary progressive multiple sclerosis (PPMS) patients detected a consistent heterogeneity in the rate of disability accumulation.
  
  
  
  To identify subgroups of PPMS patients with similar longitudinal trajectories of Expanded Disability Status Scale (EDSS) over time.
  
  
  
  All PPMS patients collected within the MSBase registry, who had their first EDSS assessment within 5 years from onset, were included in the analysis. Longitudinal EDSS scores were modeled by a latent class mixed model (LCMM), using a nonlinear function of time from onset. LCMM is an advanced statistical approach that models heterogeneity between patients by classifying them into unobserved groups showing similar characteristics.
  
  
  
  A total of 853 PPMS (51.7% females) from 24 countries with a mean age at onset of 42.4 years (standard deviation (SD): 10.8 years), a median baseline EDSS of 4 (interquartile range (IQR): 2.5-5.5), and 2.4 years of disease duration (SD: 1.5 years) were included. LCMM detected three different subgroups of patients with a mild ( n = 143; 16.8%), moderate ( n = 378; 44.3%), or severe ( n = 332; 38.9%) disability trajectory. The probability of reaching EDSS 6 at 10 years was 0%, 46.4%, and 81.9% respectively.
  
  
  
  Applying an LCMM modeling approach to long-term EDSS data, it is possible to identify groups of PPMS patients with different prognosis.
authors.affiliation: Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genova, Italy.
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authors.lastname: Signori
authors.affiliation: Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Guillermo
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authors.lastname: Izquierdo
authors.affiliation: Department of Biomedical and Neuromotor Sciences(DIBINEM), Alma Mater Studiorum, University of Bologna, Italy/IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.affiliation: Zuyderland Ziekenhuis, Sittard, The Netherlands.
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authors.affiliation: Clinique Neuro Rive-Sud, Greenfield Park, QC, Canada.
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authors.affiliation: Nuovo Ospedale Civile S. Agostino-Estense, Modena, Italy.
authors.forename: Patrizia
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authors.lastname: Sola
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Dana
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authors.lastname: Horakova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Hôpital Notre-Dame, Montreal, QC, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: Hôpital Notre-Dame, Montreal, QC, Canada.
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authors.lastname: Girard
authors.affiliation: Hôpital Notre-Dame, Montreal, QC, Canada.
authors.forename: Pierre
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authors.lastname: Duquette
authors.affiliation: KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.
authors.forename: Cavit
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authors.affiliation: Centre de Réadaptation En Déficience Physique Chaudière-Appalache, Levis, QC, Canada.
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authors.lastname: Grammond
authors.affiliation: Medical Faculty, Ondokuz Mayis University, Samsun, Turkey.
authors.forename: Murat
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authors.affiliation: Bombay Hospital Institute of Medical Sciences (BHIMS), Mumbai, India.
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authors.affiliation: Amiri Hospital, Kuwait City, Kuwait.
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authors.affiliation: Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
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authors.affiliation: Hospital Clinico San Carlos, Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.affiliation: Azienda Ospedaliera di Rilievo Nazionale, San Giuseppe Moscati, Avellino, Italy.
authors.forename: Daniele
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authors.lastname: Spitaleri
authors.affiliation: Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Vahid
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authors.lastname: Shaygannejad
authors.affiliation: Box Hill Hospital, Melbourne, VIC, Australia/Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Helmut
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authors.lastname: Butzkueven
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Tomas
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authors.lastname: Kalincik
authors.affiliation: Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Vilija
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authors.lastname: Jokubaitis
authors.affiliation: Flinders University and Medical Centre, Adelaide, SA, Australia.
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authors.lastname: Slee
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authors.affiliation: Hospital de Galdakao-Usansolo, Galdakao, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Sanchez-Menoyo
authors.affiliation: UOC Neurologia, Azienda Sanitaria Unica Regionale Marche, Macerata, Italy.
authors.forename: Eugenio
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authors.lastname: Pucci
authors.affiliation: University of Parma, Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Granella
authors.affiliation: Hunter Medical Research Institute, The University of Newcastle, Newcastle, NSW, Australia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.affiliation: Ospedali Riuniti di Salerno, Salerno, Italy.
authors.forename: Gerardo
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authors.lastname: Iuliano
authors.affiliation: Craigavon Area Hospital, Craigavon, UK.
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authors.lastname: Hughes
authors.affiliation: C. Mondino National Neurological Institute, Pavia, Italy.
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authors.lastname: Bergamaschi
authors.affiliation: Royal Hobart Hospital, Hobart, TAS, Australia.
authors.forename: Bruce
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authors.lastname: Taylor
authors.affiliation: Groene Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Freek
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authors.lastname: Verheul
authors.affiliation: Hospital São João, Porto, Portugal.
authors.forename: Maria
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authors.lastname: Edite Rio
authors.affiliation: Department NEUROFARBA, Section Neuroscience, University of Florence, Florence, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.affiliation: Department of Neurology, Golestan University of Medical Sciences, Gorgan, Iran/Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Seyed Aidin
authors.initials: SA
authors.lastname: Sajedi
authors.affiliation: Golestan Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Majdinasab
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.affiliation: Department of Health Sciences (DISSAL), Section of Biostatistics, University of Genoa, Genova, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Maria
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mesh_terms: D000328:Adult; D000367:Age Factors; D001499:Bayes Theorem; D057210:Delayed Diagnosis; D004185:Disability Evaluation; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077272:Latent Class Analysis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000175:diagnosis / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D012042:Registries; D012737:Sex Factors
keywords: Primary progressive multiple sclerosis; clinical trials; disability; heterogeneity; long-term; trajectories