RT Journal Article
T1 Confirmed disability progression as a marker of permanent disability in multiple sclerosis.
A1 Sharmin, Sifat
A1 Bovis, Francesca
A1 Malpas, Charles
A1 Horakova, Dana
A1 Havrdova, Eva Kubala
A1 Izquierdo, Guillermo
A1 Eichau, Sara
A1 Trojano, Maria
A1 Prat, Alexandre
A1 Girard, Marc
A1 Duquette, Pierre
A1 Onofrj, Marco
A1 Lugaresi, Alessandra
A1 Grand'Maison, Francois
A1 Grammond, Pierre
A1 Sola, Patrizia
A1 Ferraro, Diana
A1 Terzi, Murat
A1 Gerlach, Oliver
A1 Alroughani, Raed
A1 Boz, Cavit
A1 Shaygannejad, Vahid
A1 van Pesch, Vincent
A1 Cartechini, Elisabetta
A1 Kappos, Ludwig
A1 Lechner-Scott, Jeannette
A1 Bergamaschi, Roberto
A1 Turkoglu, Recai
A1 Solaro, Claudio
A1 Iuliano, Gerardo
A1 Granella, Franco
A1 Van Wijmeersch, Bart
A1 Spitaleri, Daniele
A1 Slee, Mark
A1 McCombe, Pamela
A1 Prevost, Julie
A1 Ampapa, Radek
A1 Ozakbas, Serkan
A1 Sanchez-Menoyo, Jose Luis
A1 Soysal, Aysun
A1 Vucic, Steve
A1 Petersen, Thor
A1 de Gans, Koen
A1 Butler, Ernest
A1 Hodgkinson, Suzanne
A1 Sidhom, Youssef
A1 Gouider, Riadh
A1 Cristiano, Edgardo
A1 Castillo-Triviño, Tamara
A1 Saladino, Maria Laura
A1 Barnett, Michael
A1 Moore, Fraser
A1 Rozsa, Csilla
A1 Yamout, Bassem
A1 Skibina, Olga
A1 van der Walt, Anneke
A1 Buzzard, Katherine
A1 Gray, Orla
A1 Hughes, Stella
A1 Sempere, Angel Perez
A1 Singhal, Bhim
A1 Fragoso, Yara
A1 Shaw, Cameron
A1 Kermode, Allan
A1 Taylor, Bruce
A1 Simo, Magdolna
A1 Shuey, Neil
A1 Al-Harbi, Talal
A1 Macdonell, Richard
A1 Dominguez, Jose Andres
A1 Csepany, Tunde
A1 Sirbu, Carmen Adella
A1 Sormani, Maria Pia
A1 Butzkueven, Helmut
A1 Kalincik, Tomas
K1 CLARITY
K1 clinical trial
K1 functional system impairment
K1 risk scoring
K1 sustained disability progression
AB 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. 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. 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). 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.
YR 2022
FD 2022-06-09
LK http://hdl.handle.net/10668/19954
UL http://hdl.handle.net/10668/19954
LA en
DS RISalud
RD Apr 19, 2025