4.3 Article

Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): Age is a key contributor to presentation

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MULTIPLE SCLEROSIS JOURNAL
卷 27, 期 13, 页码 2062-2076

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SAGE PUBLICATIONS LTD
DOI: 10.1177/1352458520988637

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Multiple sclerosis; phenotypes; disease progression; magnetic resonance imaging; age

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The NO.MS data set contains information on over 35,000 patients and shows that disease activity and worsening differ across ages and phenotypes. Young patients benefit most from treatment, with disease activity highest in pediatric patients.
Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis-Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients' baseline age, using phase III study data (approximate to 8000 patients). Results: NO.MS contains data of approximate to 35,000 patients (>200,000 brain images from approximate to 10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%-75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.

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