Evidence map›Paper›PMID 41664380›Full record

Trial reportEuropean journal of neurology2026

Vascular Comorbidities and an Increased Comorbidity Score Are Associated With Disability and Disability Progression in Secondary Progressive Multiple Sclerosis.

Nevin A John, Yingtong Li, Floriana De Angelis, Ferran Prados Carrasco, Jon Stutters, Anisha Doshi, Alberto Calvi, Domenico Plantone, Thomas Williams, Thanh Phan and 2 more

Registry-linked trialAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01910259 (A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01910259 phase2completednot on this map

A Multi-arm Phase IIB Randomised, Double Blind Placebo-controlled Clinical Trial Comparing the Efficacy of Three Neuroprotective Drugs in Secondary Progressive Multiple Sclerosis.

TypeinterventionalSponsorUniversity College, LondonRan2014 to 2018Enrolled445ConditionsSecondary Progressive Multiple SclerosisArmsAmiloride, Riluzole, Fluoxetine, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Genetic Risk Factors of Neurodegeneration: The Role ofJournal of clinical medicine · 2026
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Nevin A JohnDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.ORCID 0000-0002-9834-4498
Yingtong LiDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Floriana De AngelisDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Ferran Prados CarrascoDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Jon StuttersDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Anisha DoshiDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Alberto CalviLaboratory of Advanced Imaging in Neuroimmunological Diseases (imaginEM), Fundació de Recerca Clínic Barcelona - Institut d'Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain.
Domenico PlantoneDepartment of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy.
Thomas WilliamsDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
Thanh PhanDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
Jeremy ChatawayDepartment of Neuroinflammation, Queen Square Multiple Sclerosis Centre, UCL Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
MS‐SMART Investigators

Funding

Efficacy and Mechanism Evaluation Programme
6 · The paper itself

Abstract

backgroundVascular risk factors are associated with increased disease activity and disability progression in multiple sclerosis (MS). This has been studied mainly in cohorts with relapsing-remitting MS. However, the association between vascular comorbidities (VCM) and clinical disability in secondary progressive MS (SPMS) is less well studied. Our aim was to investigate the association between VCM, non-VCM, comorbidity burden and both physical and cognitive performance in SPMS.

methodsLongitudinal analysis of 445 patients from the MS secondary progressive multi-arm trial (MS-SMART)-a multi-arm multicentre phase-2b randomised placebo-controlled trial of three agents in SPMS (NCT01910259). VCM (hypertension and hyperlipidaemia) and non-VCM (asthma, hypothyroidism and osteoporosis) were recorded. A comorbidity score was also determined (0, 1, ≥ 2). Physical disability and processing speed were assessed at baseline, 48- and 96 weeks. Multiple linear regression and mixed models were used to investigate the cross-sectional and longitudinal relationships between baseline VCM, non-VCM, comorbidity score and clinical outcome measures.

resultsThe cohort was predominantly female (67%), median Expanded Disability Status Scale (EDSS) 6.0. 13% and 9% had hypertension and hyperlipidaemia (VCM), respectively. 7%, 9% and 5% had asthma, hypothyroidism and osteoporosis (non-VCM), respectively. Co-morbidity counts were 0,63%; 1, 23% and with > = 2, 11%. In cross-sectional models, both hypertension (β = 0.36, 95% CI 0.18-0.54) and an increased comorbidity count (β = 0.47, 95% CI 0.28-0.67) were associated with higher EDSS scores. In longitudinal models, hyperlipidaemia (β = 0.22, 95% CI 0.02-0.42) and increased comorbidity count (β = 0.21, 95% CI 0.01-0.41) were associated with increased EDSS scores over 48/96 weeks. No associations were seen with the non-VCM.

conclusionVCM and also increased comorbidity burden per se are associated with increased disability. Disability worsening over 96 weeks was most evident in those with hyperlipidaemia and increased comorbidity burden.

Indexed as

HyperlipidemiasHypertensionMultiple Sclerosis, Chronic ProgressiveOsteoporosisAdultComorbidityDisability EvaluationDisease ProgressionFemaleHumansHypothyroidismLongitudinal StudiesMaleMiddle Agedcomorbiditiesmultiple sclerosissecondary progressive

Identifiers

PMID41664380
PMCPMC12886752

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.