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

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.

Slowing of brain atrophy with teriflunomide and delayed conversion to clinically definite MS

“…Numerical reductions in CGM and WB atrophy with teriflunomide versus placebo were apparent in both subgroups, although many comparisons did not reach statistical significance, potentially due to small numbers of patients in the subgroups and the relative resistance of CGM to pseudoatrophy compared with WB as we have previously shown. 15 …”

“…Collectively, these results extend previous findings of a reduction in brain atrophy with teriflunomide in patients with relapsing MS to those patients with CIS, and align with new data suggesting that teriflunomide-treated MS patients had slower rates of whole brain, GM, WM, and thalamic atrophy over 12 months versus age- and sex-matched healthy controls. 14 – 16 , 21 Moreover, compared with dimethyl fumarate, a recent head-to-head study suggested that teriflunomide had a superior effect on the preservation of CGM and WB volume over 15−24 months. 15 , 16 …”

“…14 – 16 , 21 Moreover, compared with dimethyl fumarate, a recent head-to-head study suggested that teriflunomide had a superior effect on the preservation of CGM and WB volume over 15−24 months. 15 , 16 …”

“…[14][15][16]21 Moreover, compared with dimethyl fumarate, a recent headto-head study suggested that teriflunomide had a superior effect on the preservation of CGM and WB volume over 15−24 months. 15,16 We also found that slower rates of CGM and WB atrophy in years 1-2 of the TOPIC study were associated with a lower risk of conversion to CDMS over the 1-2 and 1-5-year timeframes. For every 1% decrease in CGM, the risk of CDMS conversion increased by 14.5% (years 1-2) and 6.6% (years 1-5), while for every 1% decrease in WB, the risk of CDMS conversion increased by 47.3% (years 1-2) and by 35.9% (years 1-5).…”

“…Recent evidence in relapsing MS patients suggests teriflunomide may slow cortical GM (CGM) and WB atrophy. 14 – 16 …”