Effect of Teriflunomide and Dimethyl Fumarate on Cortical Atrophy and Leptomeningeal Inflammation in Multiple Sclerosis: A Retrospective, Observational, Case-Control Pilot Study.

Robert Zivadinov,Channa Kolb,Michael Dwyer,Niels Bergsland,Deepa Ramasamy,Bianca Weinstock-Guttman,Jesper Hagemeier,Alexis Lizarraga,David Hojnacki,Ellen Carl

doi:10.3390/jcm8030344

Robert Zivadinov, Channa Kolb + Show 8 more

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https://doi.org/10.3390/jcm8030344

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Abstract

Background: Pathologic changes in cortical gray matter (GM) and leptomeninges contribute to disability worsening in patients with multiple sclerosis (MS), but there is little evidence whether disease-modifying treatments can slow down cortical pathology in MS. Objectives: To investigate the effect of teriflunomide (TFM) and dimethyl fumarate (DMF) in reducing cortical pathology, as determined by percentage cortical volume change (PCVC) and leptomeningeal contrast enhancement (LMCE) on MRI. Methods: This was a retrospective, single-center, observational study that selected 60 TFM- and 60 DMF-treated MS patients over 24 months. Results: TFM had a lower rate of PCVC compared to DMF over 24 months (−0.2% vs. −2.94%, p = 0.004). Similar results were observed for percentage GM volume change over 0–12 (p = 0.044) and 0–24 (−0.44% vs. −3.12%, p = 0.015) months. No significant differences were found between the TFM and DMF groups in the frequency and number of LMCE foci over the follow-up. TFM showed a numerically lower rate of whole brain atrophy over 24 months (p = 0.077), compared to DMF. No significant clinical or MRI lesion differences between TFM and DMF were detected over follow-up. Conclusions: These findings suggest that TFM has a superior effect on the preservation of cortical GM volume, compared to DMF.

Highlights

Cortical gray matter (GM) pathology in multiple sclerosis (MS) is characterized by the presence of cortical subpial lesions [1] and leptomeningeal (LM) inflammation [2,3]
Inclusion criteria were: (1) patient diagnosed with MS according to McDonald criteria [29], (2) age 18–65, (3) relapsing disease course, (4) Expanded Disability Status Scale (EDSS) ≤5.5, (5) MRI obtained on 1.5T or 3T using standardized MRI protocol, (6) patients treated with 14 mg of TFM once daily or dimethyl fumarate (DMF) 240 mg twice daily for at least three consecutive months, and (7) obtaining MRI within a 30 day window prior to staring the disease-modifying therapies (DMTs)
There were no differences between the groups in age (p = 0.879), age at onset (p = 0.869), sex (p = 0.820), disease duration (p = 0.674), relapse rate in previous 12 (p = 0.351) or 24 (p = 0.779) months, or in the EDSS score (p = 0.377)

Summary

Introduction

Cortical gray matter (GM) pathology in multiple sclerosis (MS) is characterized by the presence of cortical subpial lesions [1] and leptomeningeal (LM) inflammation [2,3]. The clinical validity of the assessments of cortical atrophy and leptomeningeal contrast enhancement (LMCE) has been demonstrated in a number of recent short-, mid-, and long-term studies [2,4,6,7,8,9]. Pathologic changes in cortical gray matter (GM) and leptomeninges contribute to disability worsening in patients with multiple sclerosis (MS), but there is little evidence whether disease-modifying treatments can slow down cortical pathology in MS. Objectives: To investigate the effect of teriflunomide (TFM) and dimethyl fumarate (DMF) in reducing cortical pathology, as determined by percentage cortical volume change (PCVC) and leptomeningeal contrast enhancement (LMCE) on MRI. Conclusions: These findings suggest that TFM has a superior effect on the preservation of cortical GM volume, compared to DMF

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