Journal article
Confirmed disability progression as a marker of permanent disability in multiple sclerosis
European Journal of Neurology, Vol.29(8), pp.2321-2334
2022
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.
Details
- Title
- Confirmed disability progression as a marker of permanent disability in multiple sclerosis
- Authors/Creators
- S. Sharmin (Author/Creator) - The University of MelbourneF. Bovis (Author/Creator) - University of GenoaC. Malpas (Author/Creator) - The University of MelbourneD. Horakova (Author/Creator) - Charles UniversityE.K. Havrdova (Author/Creator) - Charles UniversityG. Izquierdo (Author/Creator) - Hospital Universitario Virgen MacarenaS. Eichau (Author/Creator) - Hospital Universitario Virgen MacarenaM. Trojano (Author/Creator) - University of Bari Aldo MoroA. Prat (Author/Creator) - Hôpital Notre-DameM. Girard (Author/Creator) - Hôpital Notre-DameP. Duquette (Author/Creator) - Hôpital Notre-DameM. Onofrj (Author/Creator) - University of Chieti-PescaraA. Lugaresi (Author/Creator) - Istituto delle Scienze Neurologiche di BolognaF. Grand'Maison (Author/Creator) - Montreal Neurological Institute and HospitalP. Grammond (Author/Creator) - Centre Intégré de Santé et Services Sociaux de Chaudière-AppalacheP. 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 UniversityO. Gerlach (Author/Creator) - Zuyderland Medisch CentrumR. Alroughani (Author/Creator) - Amiri HospitalC. Boz (Author/Creator) - Farabi HastanesiV. Shaygannejad (Author/Creator) - Isfahan University of Medical SciencesV. van Pesch (Author/Creator) - Cliniques Universitaires Saint-LucE. Cartechini (Author/Creator) - Unica CorporationL. Kappos (Author/Creator) - University Hospital of BaselJ. Lechner‐Scott (Author/Creator)R. Bergamaschi (Author/Creator) - IRCCS Mondino Foundation, Pavia, Italy.R. Turkoglu (Author/Creator) - Haydarpaşa Numune Eğitim ve Araştırma HastanesiC. Solaro (Author/Creator) - Department of Rehabilitaiton, ML Novarese Hospital Moncrivello, Italy.G. Iuliano (Author/Creator) - Ospedali Riuniti San Giovanni di Dio e Ruggi d'AragonaF. Granella (Author/Creator) - University of ParmaB. Van Wijmeersch (Author/Creator) - Hasselt UniversityD. Spitaleri (Author/Creator) - Azienda Ospedaliera S.Giuseppe MoscatiM. Slee (Author/Creator) - Flinders UniversityP. McCombe (Author/Creator) - Royal Brisbane and Women's HospitalJ. Prevost (Author/Creator) - Cegep de Saint JeromeR. Ampapa (Author/Creator) - Hospital JihlavaS. Ozakbas (Author/Creator) - Dokuz Eylül UniversityJ.L. Sanchez‐Menoyo (Author/Creator)A. Soysal (Author/Creator) - Bakırköy Psychiatric HospitalS. Vucic (Author/Creator) - Westmead HospitalT. Petersen (Author/Creator) - Aarhus University HospitalK. de Gans (Author/Creator) - Groene Hart ZiekenhuisE. Butler (Author/Creator) - Monash Medical CentreS. Hodgkinson (Author/Creator) - Liverpool HospitalY. Sidhom (Author/Creator) - Hôpital Razi de La ManoubaR. Gouider (Author/Creator) - Hôpital Razi de La ManoubaE. Cristiano (Author/Creator) - Hospital Italiano de Buenos AiresT. Castillo‐Triviño (Author/Creator)M.L. Saladino (Author/Creator) - Institute of NeuroscienceM. Barnett (Author/Creator) - Mind (Poland)F. Moore (Author/Creator) - Jewish General HospitalC. Rozsa (Author/Creator) - Jahn Ferenc Dél-Pesti Kórház és RendelőintézetB. Yamout (Author/Creator) - American University of BeirutO. Skibina (Author/Creator) - Monash UniversityA. van der Walt (Author/Creator) - Monash UniversityK. Buzzard (Author/Creator) - Monash UniversityO. Gray (Author/Creator) - South Eastern Health and Social Care TrustS. Hughes (Author/Creator) - Craigavon Area HospitalA.P. Sempere (Author/Creator) - Hospital General Universitario de Alicante Doctor BalmisB. Singhal (Author/Creator) - Bombay HospitalY. Fragoso (Author/Creator) - Universidade Metropolitana de SantosC. Shaw (Author/Creator) - Geelong HospitalA. Kermode (Author/Creator) - Sir Charles Gairdner HospitalB. Taylor (Author/Creator) - Royal Hobart HospitalM. Simo (Author/Creator) - Semmelweis UniversityN. Shuey (Author/Creator) - St Vincent's HealthT. Al‐Harbi (Author/Creator)R. Macdonell (Author/Creator) - Austin HealthJ.A. Dominguez (Author/Creator) - Hospital de La RiberaT. Csepany (Author/Creator) - University of DebrecenC.A. Sirbu (Author/Creator) - Titu Maiorescu UniversityM.P. Sormani (Author/Creator) - University of GenoaH. Butzkueven (Author/Creator) - Monash UniversityT. 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