Confirmed disability progression as a marker of permanent disability in multiple sclerosis

S. Sharmin; F. Bovis; C. Malpas; D. Horakova; E.K. Havrdova; G. Izquierdo; S. Eichau; M. Trojano; A. Prat; M. Girard; P. Duquette; M. Onofrj; A. Lugaresi; F. Grand'Maison; P. Grammond; P. Sola; D. Ferraro; M. Terzi; O. Gerlach; R. Alroughani; C. Boz; V. Shaygannejad; V. van Pesch; E. Cartechini; L. Kappos; J. Lechner‐Scott; R. Bergamaschi; R. Turkoglu; C. Solaro; G. Iuliano; F. Granella; B. Van Wijmeersch; D. Spitaleri; M. Slee; P. McCombe; J. Prevost; R. Ampapa; S. Ozakbas; J.L. Sanchez‐Menoyo; A. Soysal; S. Vucic; T. Petersen; K. de Gans; E. Butler; S. Hodgkinson; Y. Sidhom; R. Gouider; E. Cristiano; T. Castillo‐Triviño; M.L. Saladino; M. Barnett; F. Moore; C. Rozsa; B. Yamout; O. Skibina; A. van der Walt; K. Buzzard; O. Gray; S. Hughes; A.P. Sempere; B. Singhal; Y. Fragoso; C. Shaw; A. Kermode; B. Taylor; M. Simo; N. Shuey; T. Al‐Harbi; R. Macdonell; J.A. Dominguez; T. Csepany; C.A. Sirbu; M.P. Sormani; H. Butzkueven; T. Kalincik

doi:10.1111/ene.15406

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Confirmed disability progression as a marker of permanent disability in multiple sclerosis

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Confirmed disability progression as a marker of permanent disability in multiple sclerosis

S. Sharmin, F. Bovis, C. Malpas, D. Horakova, E.K. Havrdova, G. Izquierdo, S. Eichau, M. Trojano, A. Prat, M. Girard, …

European Journal of Neurology, Vol.29(8), pp.2321-2334

2022

DOI: https://doi.org/10.1111/ene.15406

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Abstract

Background and purpose The prevention of disability over the long term is the main treatment goal in multiple sclerosis (MS); however, randomized clinical trials evaluate only short-term treatment effects on disability. This study aimed to define criteria for 6-month confirmed disability progression events of MS with a high probability of resulting in sustained long-term disability worsening. Methods In total, 14,802 6-month confirmed disability progression events were identified in 8741 patients from the global MSBase registry. For each 6-month confirmed progression event (13,321 in the development and 1481 in the validation cohort), a sustained progression score was calculated based on the demographic and clinical characteristics at the time of progression that were predictive of long-term disability worsening. The score was externally validated in the Cladribine Tablets Treating Multiple Sclerosis Orally (CLARITY) trial. Results The score was based on age, sex, MS phenotype, relapse activity, disability score and its change from baseline, number of affected functional system domains and worsening in six of the domains. In the internal validation cohort, a 61% lower chance of improvement was estimated with each unit increase in the score (hazard ratio 0.39, 95% confidence interval 0.29–0.52; discriminatory index 0.89). The proportions of progression events sustained at 5 years stratified by the score were 1: 72%; 2: 88%; 3: 94%; 4: 100%. The results of the CLARITY trial were confirmed for reduction of disability progression that was >88% likely to be sustained (events with score ˃1.5). Conclusions Clinicodemographic characteristics of 6-month confirmed disability progression events identify those at high risk of sustained long-term disability. This knowledge will allow future trials to better assess the effect of therapy on long-term disability accrual.

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Title: Confirmed disability progression as a marker of permanent disability in multiple sclerosis
Authors/Creators: S. Sharmin (Author/Creator) - The University of Melbourne
F. Bovis (Author/Creator) - University of Genoa
C. Malpas (Author/Creator) - The University of Melbourne
D. Horakova (Author/Creator) - Charles University
E.K. Havrdova (Author/Creator) - Charles University
G. Izquierdo (Author/Creator) - Hospital Universitario Virgen Macarena
S. Eichau (Author/Creator) - Hospital Universitario Virgen Macarena
M. Trojano (Author/Creator) - University of Bari Aldo Moro
A. Prat (Author/Creator) - Hôpital Notre-Dame
M. Girard (Author/Creator) - Hôpital Notre-Dame
P. Duquette (Author/Creator) - Hôpital Notre-Dame
M. Onofrj (Author/Creator) - University of Chieti-Pescara
A. Lugaresi (Author/Creator) - Istituto delle Scienze Neurologiche di Bologna
F. Grand'Maison (Author/Creator) - Montreal Neurological Institute and Hospital
P. Grammond (Author/Creator) - Centre Intégré de Santé et Services Sociaux de Chaudière-Appalache
P. Sola (Author/Creator) - Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.
D. Ferraro (Author/Creator) - Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.
M. Terzi (Author/Creator) - Ondokuz Mayıs University
O. Gerlach (Author/Creator) - Zuyderland Medisch Centrum
R. Alroughani (Author/Creator) - Amiri Hospital
C. Boz (Author/Creator) - Farabi Hastanesi
V. Shaygannejad (Author/Creator) - Isfahan University of Medical Sciences
V. van Pesch (Author/Creator) - Cliniques Universitaires Saint-Luc
E. Cartechini (Author/Creator) - Unica Corporation
L. Kappos (Author/Creator) - University Hospital of Basel
J. Lechner‐Scott (Author/Creator)
R. Bergamaschi (Author/Creator) - IRCCS Mondino Foundation, Pavia, Italy.
R. Turkoglu (Author/Creator) - Haydarpaşa Numune Eğitim ve Araştırma Hastanesi
C. Solaro (Author/Creator) - Department of Rehabilitaiton, ML Novarese Hospital Moncrivello, Italy.
G. Iuliano (Author/Creator) - Ospedali Riuniti San Giovanni di Dio e Ruggi d'Aragona
F. Granella (Author/Creator) - University of Parma
B. Van Wijmeersch (Author/Creator) - Hasselt University
D. Spitaleri (Author/Creator) - Azienda Ospedaliera S.Giuseppe Moscati
M. Slee (Author/Creator) - Flinders University
P. McCombe (Author/Creator) - Royal Brisbane and Women's Hospital
J. Prevost (Author/Creator) - Cegep de Saint Jerome
R. Ampapa (Author/Creator) - Hospital Jihlava
S. Ozakbas (Author/Creator) - Dokuz Eylül University
J.L. Sanchez‐Menoyo (Author/Creator)
A. Soysal (Author/Creator) - Bakırköy Psychiatric Hospital
S. Vucic (Author/Creator) - Westmead Hospital
T. Petersen (Author/Creator) - Aarhus University Hospital
K. de Gans (Author/Creator) - Groene Hart Ziekenhuis
E. Butler (Author/Creator) - Monash Medical Centre
S. Hodgkinson (Author/Creator) - Liverpool Hospital
Y. Sidhom (Author/Creator) - Hôpital Razi de La Manouba
R. Gouider (Author/Creator) - Hôpital Razi de La Manouba
E. Cristiano (Author/Creator) - Hospital Italiano de Buenos Aires
T. Castillo‐Triviño (Author/Creator)
M.L. Saladino (Author/Creator) - Institute of Neuroscience
M. Barnett (Author/Creator) - Mind (Poland)
F. Moore (Author/Creator) - Jewish General Hospital
C. Rozsa (Author/Creator) - Jahn Ferenc Dél-Pesti Kórház és Rendelőintézet
B. Yamout (Author/Creator) - American University of Beirut
O. Skibina (Author/Creator) - Monash University
A. van der Walt (Author/Creator) - Monash University
K. Buzzard (Author/Creator) - Monash University
O. Gray (Author/Creator) - South Eastern Health and Social Care Trust
S. Hughes (Author/Creator) - Craigavon Area Hospital
A.P. Sempere (Author/Creator) - Hospital General Universitario de Alicante Doctor Balmis
B. Singhal (Author/Creator) - Bombay Hospital
Y. Fragoso (Author/Creator) - Universidade Metropolitana de Santos
C. Shaw (Author/Creator) - Geelong Hospital
A. Kermode (Author/Creator) - Sir Charles Gairdner Hospital
B. Taylor (Author/Creator) - Royal Hobart Hospital
M. Simo (Author/Creator) - Semmelweis University
N. Shuey (Author/Creator) - St Vincent's Health
T. Al‐Harbi (Author/Creator)
R. Macdonell (Author/Creator) - Austin Health
J.A. Dominguez (Author/Creator) - Hospital de La Ribera
T. Csepany (Author/Creator) - University of Debrecen
C.A. Sirbu (Author/Creator) - Titu Maiorescu University
M.P. Sormani (Author/Creator) - University of Genoa
H. Butzkueven (Author/Creator) - Monash University
T. Kalincik (Author/Creator) - The University of Melbourne
Publication Details: European Journal of Neurology, Vol.29(8), pp.2321-2334
Publisher: John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Identifiers: 991005544254507891
Copyright: © 2022 The Authors.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.147 Multiple Sclerosis
Web Of Science research areas: Clinical Neurology; Neurosciences
ESI research areas: Neuroscience & Behavior