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Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

ABSTRACT: Key unmet needs in multiple sclerosis (MS) include detection of early pathology, disability worsening independent of relapses, and accurate monitoring of treatment response. Collaborative approaches to address these unmet needs have been driven in part by industry-academic networks and initiatives such as the Grant for Multiple Sclerosis Innovation (GMSI) and Multiple Sclerosis Leadership and Innovation Network (MS-LINK^™) programs. We review the application of recent advances, supported by the GMSI and MS-LINK^™ programs, in neuroimaging technology to quantify pathology related to central pathology and disease worsening, and potential for their translation into clinical practice/trials. GMSI-supported advances in neuroimaging methods and biomarkers include developments in magnetic resonance imaging, positron emission tomography, ocular imaging, and machine learning. However, longitudinal studies are required to facilitate translation of these measures to the clinic and to justify their inclusion as endpoints in clinical trials of new therapeutics for MS. Novel neuroimaging measures and other biomarkers, combined with artificial intelligence, may enable accurate prediction and monitoring of MS worsening in the clinic, and may also be used as endpoints in clinical trials of new therapies for MS targeting relapse-independent disease pathology.

SUBMITTER: Oh J

PROVIDER: S-EPMC10722910 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

Oh Jiwon J Airas Laura L Harrison Daniel D Järvinen Elina E Livingston Terrie T Lanker Stefan S Malik Rayaz A RA Okuda Darin T DT Villoslada Pablo P de Vries Helga E HE

Frontiers in neurology 20231201

Key unmet needs in multiple sclerosis (MS) include detection of early pathology, disability worsening independent of relapses, and accurate monitoring of treatment response. Collaborative approaches to address these unmet needs have been driven in part by industry-academic networks and initiatives such as the Grant for Multiple Sclerosis Innovation (GMSI) and Multiple Sclerosis Leadership and Innovation Network (MS-LINK<sup>™</sup>) programs. We review the application of recent advances, support ...[more]

PMID: 38107636

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Project description:Background and objectivesDisease activity in multiple sclerosis (MS) is highly variable, and there are limited prospective studies on predictors of disease outcomes. The goal of this study is to identify and assess patient characteristics in MS that predict disease activity and worsening.MethodsThe study population consisted of a prospective cohort of 1,008 participants with relapsing-remitting onset MS enrolled in the CombiRx trial. Cox regression analysis was used to determine hazard ratio (HR) associations between baseline (BL) demographics, clinical history, MRI metrics, and treatment with outcomes of time to first new disease activity over up to 7 years of follow-up including relapse, MRI activity, and disease worsening.ResultsOne thousand eight participants were randomized, with 959 eligible for assessment of disease activity and worsening on follow-up. In multivariable models, the risk of relapse was higher in participants younger than 38 years at BL than in those older (HR range 1.36-1.43), with the presence of gadolinium (Gd)+ lesions at BL (HR 1.38, [95% confidence interval, CI 1.14, 1.67]) and with BL EDSS ≥3.5 vs <3.5 (HR range 1.63-1.67). The risk of new MRI activity was higher in younger participants (HR range 1.58-1.84), with higher preexisting lesion counts greater than the median lesion count with ≥71 T2 hyperintense lesions vs <71 (HR 1.50, [95% CI 1.27, 1.77]), with the presence of BL Gd+ lesions (HR 1.75, [95% CI 1.49, 2.06]), and higher BL T2 lesion volume (HR 1.02 for every unit increase in baseline volume, [95% CI 1.01, 1.03]). The risk of new MRI activity was lower in those receiving combination therapy compared with those that in those receiving either glatiramer acetate (HR range 0.67-0.68) or interferon beta-1a (HR range 0.68-0.70). The risk of disease worsening was higher for those with higher T2 volume (HR for 1 unit increase in volume 1.01, 95% CI 1.004, 1.03) and BL EDSS <2 (HR range 2.79-2.96). There were no associations between sex, race, and disease duration on relapse, MRI activity, or disease worsening in the multivariable analysis.DiscussionProspective data from a large clinical trial cohort show that younger MS patients with high BL relapses and MRI lesion burden have the highest risk of subsequent disease activity.Trial registration informationClinical trial registration number NCT00211887. CombiRx was registered at ClinicalTrials.gov (NCT00211887) on September 21, 2005. Study enrollment began in January 2005.

Project description:OBJECTIVE:Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. METHODS:We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. RESULTS:SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION:This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222.

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Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

Publications

Neuroimaging to monitor worsening of multiple sclerosis: advances supported by the grant for multiple sclerosis innovation.

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