More evidence for the memory B..this time from teriflunomide

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This week we have another study showing the effect of MS drugs on memory B cells…Guess what it… It shows essentially no effect on the percentage of memory B cells……:-(. Ooops

Teriflunomide induces a tolerogenic bias in blood immune cells of MS patients.Medina S, Sainz de la Maza S, Villarrubia N, Álvarez-Lafuente R, Costa-Frossard L, Arroyo R, Monreal E, Tejeda-Velarde A, Rodríguez-Martín E, Roldán E, Álvarez-Cermeño JC, Villar LM. Ann Clin Transl Neurol. 2019 Jan 15;6(2):355-363

Objectives :Teriflunomide, a disease‐modifying treatment approved for multiple sclerosis (MS), inhibits reversibly dihydroorotate dehydrogenase, an enzyme involved in de novo pyrimidine biosynthesis and down‐regulates proliferation of activated lymphocytes. We aimed to study the impact of this drug in the lymphocyte profiles of MS patients.

Methods:Fifty‐five patients with relapsing‐remitting MS who initiated teriflunomide treatment were included in the study. We studied peripheral blood mononuclear cells obtained before and 6 months after treatment initiation and explored effector, memory, and regulatory cells by flow cytometry. Wilcoxon matched pair tests were used to assess differences between basal and 6 months after treatment results. P‐values were corrected with Bonferroni test.

Results: When explored T and B cell subsets, we observed a decrease in the percentages of terminally differentiated CD4+ T cells (P = 0.001) and plasmablasts (P < 0.0001) after 6 months of treatment. These results were confirmed with the total cell number. When studied immunomodulatory cells, we observed a clear increase of monocytes expressing programmed death‐ligand 1 (PD‐L1) (P = 0.005), which correlated negatively with all effector CD8+ T cell subsets. We also observed an increase in the percentage of CD8+ T cells (P = 0.028) and monocytes (P = 0.04) producing IL‐10.

Conclusions: Teriflunomide induces a specific reduction in effector T and B cells that have shown to play a role in MS course and an increase in immunomodulatory cells. Particularly, this drug induces the expression of PD‐L1, a molecule involved in tolerance to autoantigens, which can contribute to inhibit the abnormal immune response taking place in MS.

Does this worry me?…Well not really… as it reinforces what I think..

Yes, we should be dumping the CRAB-type drugs, as they are simply not good enough for the masses.

COI: Multiple but None considered relevant

So there we go….it supports the concept that memory B cells are important, because word on the street is that it is not a very effective treatment. Although it does not reduce the percentage of memory B cells within the B cell pool, as the drug is reducing the B cell pool it is actually reducing B memory cells, but it simply is not that selective.

This contrast with what we hear over and over again about Glateriamer acetate. It works on this or that mechanism. This simple says the mechanism is not that important if it is majorly affected, because Glateriamer acetate is not good enough in most people.

“Response to Therapy” is the key

ProfG has made the suggestion that teri works better when it is second line. If this is true then you may see a difference in depletion of the cells when given first line and after treatment with another agent.

Maybe the authors of this paper can see if the depletion (in absolute numbers) in two such groups no previous treatment (n=13) and previous treatment with a CRAB-drug (n=35) are different. Maybe if anyone else uses teri they can answer this question perhaps, whilst they contenmplate the merits of their treatment apporach.

We can’t do this because we do not have enough people who select teriflnomide as their drug of choice..

We have asked some people and they have confirmed the observation that teri is not a good depleter of memory B’s. May I have it all wrong. Here there is a depletion of the plasmablasts (rogeny of memory B cells) in this study..maybe we have missed the key element and it is the plasma blasts.

PPS I am not a neuro

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