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

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

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.

Keywords: brain atrophy; cortical atrophy; dimethyl fumarate; leptomeningeal enhancement; multiple sclerosis; teriflunomide.

Conflict of interest statement

R.Z. received personal compensation from EMD Serono, Genzyme-Sanofi, Celgene and Novartis for speaking and consultant fees. He received financial support for research activities from Genzyme-Sanofi, Novartis, Celgene, Mapi Pharma and Protembis. N.B., E.C., D.P.R., J.H., M.G.D. and A.A.L. have nothing to disclose. C.K. has received speaker honoraria and consultant fees from EMD Serono, Teva Pharmaceuticals, Acorda, Novartis, Genzyme and Biogen-Idec. D.H. has received speaker honoraria and consultant fees from Biogen Idec, Teva Pharmaceutical Industries Ltd., EMD Serono, Pfizer Inc, and Novartis. B.W.-G. received honoraria as a speaker and as a consultant for Biogen Idec, EMD Serono, Novartis and Mallinckrodt. B.W.-G. received research funds from Biogen Idec, Teva Pharmaceuticals, EMD Serono, Genzyme & Sanofi, Novartis.

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