Early Predictors of Disability in Paediatric Multiple Sclerosis: Evidence from a Multi-National Registry (P17-4.001)
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Abstract
Objective: We sought to identify the early predictors of disability progression in a multi-national cohort of patients with paediatric-onset multiple sclerosis (POMS), considering the potential for commencing high-efficacy disease-modifying therapies (DMTs).
Background: Early recognition of markers of faster disability worsening in POMS is important for treatment decisions at the earliest possible time after symptoms onset.
Design/Methods: We identified patients who were <18 years at the onset of MS symptoms from the global MSBase registry. Patients with first neurological assessment within 12 months from symptoms onset were included. The variables examined as predictors of future MS Severity Score (MSSS; disability ranked by disease duration) included: age at symptoms onset, complete recovery from first relapse, EDSS score, relapse phenotypes and frequency during the first 12 months. The analyses were adjusted for cumulative proportion of time on high-efficacy DMTs. A Bayesian log-normal generalized linear mixed model was used to analyse the longitudinal data.
Results: 672 patients (70% women) contributing 9357 visits were included. The median (quartiles) age at symptoms onset was 16 (15–17) years. Older age at symptoms onset (exp(β)=1.09 [95% Credible Interval: 1.03,1.16]), higher EDSS score (1.25 [1.13,1.36]), and pyramidal (1.34 [1.13,1.58]), visual (1.28 [1.10,1.48]), and cerebellum (1.17 [1.00,1.39]) symptoms during the first 12 months were associated with higher MSSS. Interestingly, MSSS was reduced by 4% for each unit increase in the proportion of time on high-efficacy DMTs (0.96 [0.93,0.99]).
Conclusions: MS symptoms presented later in the childhood, higher disability, and pyramidal, visual, or cerebellum symptoms during the first year predicted significant worsening in disability in patients with paediatric MS. Persistent treatment with high-efficacy DMTs was associated with reduced rate of disability worsening.
Disclosure: Dr. Sharmin has nothing to disclose. Charles Malpas has nothing to disclose. Izanne Roos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Izanne Roos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Izanne Roos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Izanne Roos has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Izanne Roos has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Izanne Roos has received research support from MSIF-ARSEP. Izanne Roos has received research support from Melbourne Research Scholarship. Izanne Roos has received personal compensation in the range of $0-$499 for serving as a travel support with Merck. Izanne Roos has received personal compensation in the range of $0-$499 for serving as a travel support with Roche. Ibrahima Diouf has nothing to disclose. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Bayer, Novartis, Merck, Roche, Sanofi. Dr. Alroughani has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen, Novartis, Merck, Roche, Sanofi. Dr. Ozakbas has nothing to disclose. Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer, Biogen Idec, Novartis, Sanofi, Merck Serono, Roche, Actelion and Celgene. Dr. Izquierdo Ayuso has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme, Novartis, Sanofi Aventis, Alexion. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Sara Eichau Madueño has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Sara Eichau Madueño has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Sara Eichau Madueño has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Sara Eichau Madueño has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Sara Eichau Madueño has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Merck. Sara Eichau Madueño has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Novartis. Sara Eichau Madueño has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Sanofi. Sara Eichau Madueño has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen. Sara Eichau Madueño has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Teva. Sara Eichau Madueño has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Roche. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dana Horakova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Actelion. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Actelion. Dr. Havrdova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Havrdova has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Biogen. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Almirall, Bayer, Biogen, Merck, Roche, Sanofi, TEVA. Dr. Patti has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for University of Catania and AISM/FISM, Fondazione Italiana Sclerosi Multipla. Dr. Terzi has nothing to disclose. Dr. Boz has nothing to disclose. Dr. Yamout has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Yamout has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Yamout has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Yamout has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Yamout has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merk. Dr. Khoury has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ANA. Dr. Khoury has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Clinical Immunology. The institution of Dr. Khoury has received research support from MENACTRIMS. The institution of Dr. Khoury has received research support from NMSS. The institution of Dr. Khoury has received research support from Office of Naval Research USA. An immediate family member of Dr. Khoury has received intellectual property interests from a discovery or technology relating to health care. Dr. Onofrj has nothing to disclose. Dr. Lugaresi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck Serono. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis Pharma. Dr. Lugaresi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mylan. Dr. Lugaresi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Sqibb. Dr. Lugaresi has a non-compensated relationship as a Speaker at meetings, participant in trials with Fondazione Italiana Sclerosi Multipla that is relevant to AAN interests or activities. Dr. Altintas has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Dr. Altintas has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Deva. The institution of Dr. Altintas has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. The institution of Dr. Prat has received research support from CIHR and MSSC. Dr. Girard has nothing to disclose. The institution of Dr. Duquette has received research support from Biogen and Genzyme. Maria Jose Marques de Sa, Prof has nothing to disclose. Samia Ben Sassi has nothing to disclose. Dr. Sidhom has nothing to disclose. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Gouider has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Gouider has received research support from Clinical Investigation Center. The institution of Dr. Gouider has received research support from Menactrims. Dr. Soysal has nothing to disclose. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche. Yara D. Fragoso has nothing to disclose. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Health and Medical Research Council. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MS Research Australia. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for WebMD Global. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BioCSL. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Tomas Kalincik has received research support from Biogen. The institution of Tomas Kalincik has received research support from Novartis. The institution of Tomas Kalincik has received research support from Genzyme. The institution of Tomas Kalincik has received research support from Roche. The institution of Tomas Kalincik has received research support from Celgene. The institution of Tomas Kalincik has received research support from Merck. The institution of Tomas Kalincik has received research support from MSBase Foundation. The institution of Tomas Kalincik has received research support from ARSEP and EDMUS Foundations. The institution of Tomas Kalincik has received research support from MS Research Australia. The institution of Tomas Kalincik has received research support from National Health and Medical Research Council. The institution of Tomas Kalincik has received research support from Australian Research Council. The institution of Tomas Kalincik has received research support from MS Society. The institution of Tomas Kalincik has received research support from Trish Foundation. Tomas Kalincik has a non-compensated relationship as a scientific leadership group chair with MSBase Foundation that is relevant to AAN interests or activities.
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