Dimethyl fumarate for Primary Progressive MS? Is it all just MS

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Frontiers | Emerging Understanding of the Mechanism of Action for Dimethyl  Fumarate in the Treatment of Multiple Sclerosis | Neurology
Figure of DMF action from Frontiers in Neurology

A fair number of you probably take Dimethyl Fumarate (DMF) for your relapsing remitting MS, but did you realise that it may also work in Primary Progressive MS? This is what this latest piece of research suggests.

There is one basic principle to MS treatments as a whole; which is that the treatment efficacy is very much in line with the extent of immunosuppression. And if you apply this principle to PPMS then the same should occur, which is what is demonstrated here.

With paucity of treatments for PPMS, with only Ocrelizumab licensed for this group of individuals, there is an unmet need for repurposing drugs from RRMS into PPMS. DMF is yet to undergo a Phase 3 study in PPMS, a milestone needed for clinical licensing of drug for this indication.

The efficacy of DMF and it’s immunosuppressive effect compared to Ocrelizumab is low, and so is it’s clinical efficacy in PPMS. Nonetheless, the blood and CSF analysis confirm that there is depletion of T lymphocytes in the blood and spinal fluid compartment of patients on DMF compared to placebo. This is also a sure advantage of DMF over Ocrelizumab, as Ocrelizumab being an antibody doesn’t cross over in the CNS compartment and works wholly in the periphery.

So if you do the maths, and you don’t mind being on a slow burn anti-inflammatory drug for your PPMS which is more cost-effective than Ocrelizumab then it makes sense to try DMF.

If you’d like to read more about DMF in PPMS follow this link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916520/

Abstract

J Neuroimmunol. 2021 Oct 22;361:577756. doi: 10.1016/j.jneuroim.2021.577756. Online ahead of print.

Immunological effects of dimethyl fumarate treatment in blood and CSF of patients with primary progressive MS

J TalbotH Højsgaard ChowR Holm Hansen M Rode von Essen F Sellebjerg 

Dimethyl fumarate is an efficient therapy used widely in patients with relapsing-remitting multiple sclerosis (RRMS). However, lacking effect of treatment has recently been reported in patients with primary progressive MS (PPMS) (Højsgaard Chow et al., 2021). In order to further analyze the immunological treatment response we investigated the systemic and intrathecal immunological effects of dimethyl fumarate (DMF) treatment in 50 patients with PPMS who participated in a 48-week randomized controlled trial with dimethyl fumarate vs placebo. We found substantial systemic immunomodulatory effects of DMF treatment comparable with those observed in patients with RRMS. However, intrathecal effects were limited and restricted to CD4+ T cells presumably resulting in higher concentrations of intrathecal IL-7.

About the author

Neuro Doc Gnanapavan

11 comments

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  • What are professor gavins project ( basically the reason he left was to focus more on certain things and seeing them through ) since he is leaving ?

  • NDG – great post and very Prof. G like……in that you are presenting an outside of the box idea to address an unmet need of the very often overlooked PPMS population.

    I agree DMF might not be a great first line therapy for highly active RRMS (when compared to other DMTs); however, if DMF can cross the BBB and get into the CNS, it might provide a therapeutic effect on the smoldering aspects of MS and thus PPMS.

    As I was reading your post, I could not help but think about Prof. K and his use of Cladribine for PPMS. Seems to me that CLAD would be an even better candidate for the thesis presented in the above referenced manuscript.

    • Thank you, a great compliment to be compared in this way.

      Definitely Cladribine has a greater impact on the CNS, both T and B cells. If Ixazomib (SIZOMUS clinical trial) works then also anti-plasma cell activity in MS.

  • I do not understand why treatments for PPMS are not available for those with SPMS with no relapses .
    The condition seems absolutely the same …I am sceptical about all of this but having had MS since 1965 I think my input is worth while !

    • Interestingly, anti-inflammatory drugs seem to work better in SPMS than PPMS – this maybe that the overall inflammation is greater in SPMS but whether they will work as well is the question!

    • It was to be the INSPIRE study by Biogen – Phase 3 but they closed this when they didn’t get much data from the ASCEND (natalizumab in SPMS) trial. We now know that natalizumab works in UL function based on a reanalysis of the ASCEND data!

      • Thank you for your reply. Not sure whether that means DMF will be looked at again for SPMS? Or isn’t it relevant because if you don’t qualify for a DMT (natalizumab) you won’t qualify for DMF either? Not being very familiar with this topic, just trying to understand the logic here 🙂

        • I believe someone will need to resurrect both natalizumab and DMF in PPMS. Dropping the project would have been a business decision on the part of Biogen with a redirection of resources to other programs. It goes in the same bucket doing clinical trials long enough to show a difference in Progressive MS.

          • Thanks for this – hopefully resurrection will be for both types of progressive…but I won’t hold my breath!

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