Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation

Jakimovski, Dejan; Qureshi, Ferhan; Ramanathan, Murali; Jalaleddini, Kian; Ghoreyshi, Ati; Dwyer, Michael G.; Bergsland, Niels; Weinstock-Guttman, Bianca; Zivadinov, Robert

doi:10.1016/j.jns.2024.123055

Journal of the Neurological Sciences

2024

DOI: 10.1016/j.jns.2024.123055

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Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation

Dejan Jakimovski,

Ferhan Qureshi,

Murali Ramanathan

et al.

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Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study

Zivadinov,

Pei,

Clayton

et al. 2023

J Neurol Neurosurg Psychiatry

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BackgroundAtrophied T2-lesion volume (aT2-LV) is an exploratory imaging marker in multiple sclerosis (MS) reflecting the volume of lesions subsumed into cerebrospinal fluid (CSF).ObjectiveTo investigate the effect of ocrelizumab (OCR) versus placebo (PBO) over 120 weeks on the accumulation of aT2-LV in a double-blind placebo-controlled (DBP) phase 3, primary-progressive (PP) MS study (ORATORIO;NCT01194570).MethodsThis post-hoc, MRI-blinded analysis evaluated 732 PPMS randomised to OCR (488) or PBO (244). Atrophied T2-LV was calculated by overlaying baseline T2-lesion masks on follow-up CSF maps. Clinical data from DBP and open-label extension (OLE) periods were available. Treatment effect was evaluated by a mixed-effect model with repeated measures, while logistic regression explored the association of aT2-LV at week 120 and clinical outcomes in the OLE period.ResultsOCR treatment significantly reduced accumulation of aT2-LV compared with PBO (319.4 mm3vs 366.1 mm3, p=0.015) at 120 weeks. OCR showed superiority over PBO in reducing aT2-LV in patients who developed confirmed disability progression (CDP) during the DBP period at 12 (CDP12) and 24 (CDP24) weeks for the composite of Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test and Timed 25-Foot Walk test. Accumulation of aT2-LV at week 120 was related to CDP12-EDSS (p=0.018) and CDP24-EDSS (p=0.022) in the OLE for the patients who were treated by PBO in the DBP only.ConclusionsOCR showed a significant effect of reducing the accumulation of aT2-LV in PPMS in the DBP period and was related to CDP-EDSS in OLE only in the PBO arm.

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Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study

Zivadinov,

Pei,

Clayton

et al. 2023

J Neurol Neurosurg Psychiatry

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show abstract

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Glial cell injury and atrophied lesion volume as measures of chronic multiple sclerosis inflammation

Cited by 1 publication

References 37 publications

Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study

Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study

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