Teriflunomide and brain atrophy

T

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.

ProfG has been worrying some of you with the thought that cladribine and ocrelizumab are not in the same league as alemtuzumab in slowing brain volume loss. The rate of brain volume loss was about 0.1% after a few years so back to normal aging. I think ocrelizumab was about 0.3%. It maybe the case, but let’s hope not.

I think if you ask anybody they would say that they are both more effective than teriflunomide or dimethyl fumarate. So in this paper about the battle of the bottom feeders, only joking, you can see the rate of teriflunomide of brain volume loss was -0.2% so not bad. I remember seeing the data being presented at ECTRIMS and thinking the atrophy effect was much better than expected. The question is if true…what is it doing?.

Again the problem is the outcome, because an effective DMT can cause pseudoatrophy. HSCT shrinks the brain by over 3% in the first year. Is this the problem for the DMF in this study..a better anti-inflammatory effect as this rate of volume change is much worse than other studies such as this one showing rate or loss as -0.4 . So brain atrophy is a mixed bag. Grey matter volume loss is less sensitive to the arefacts of shrinkage and here the shrinkage was 0.4%. We need head to head randomised studies. There is a study ongoing looking at high efficacy verses escalation..we couldn’t do it as the neuros are not fans of the low efficacy option.

Cladribine followed by teritunomide? What do you think?

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MouseDoctor

4 comments

  • You forgot a link to the paper: https://www.mdpi.com/2077-0383/8/3/344

    I remember reading about BVL measurements being sensitive to even a really common covariates like hydration at the time of MRI. How can you be sure if the results can be skewed so easily like that? Is there any papers being done about robustness of BVL measurements?

    • “I remember reading about BVL measurements being sensitive to even a really common covariates like hydration at the time of MRI.”

      For sure..don’t any water for 2 days and you’ll feel a sharp headache kick in.

  • “I think ocrelizumab was about 0.3%. It maybe the case, but let’s hope not.’

    So in 10 years you lost 3% of your brain.
    Horrible.

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