This week ACTRIMS has been going. The academics have been microbioming and even got salt in the act as salt affects gut bacteria, but in terms of pharma news it was the reports of the phase III new sphingosine-1-phposhate modulator that is going to make the next new drug on the block.
The data published with dimethyl fumarate was not so great, but it is nice to see data replicated and so more evidence to support the idea comes from ACTRIMS. The effect on B cells was not dependent on whether DMF was associated with leucopaenia and not related to antibody levels. However we know leucopaenia puts you at extra risk from infection.
Dimethyl fumarate effects on circulating B-cell phenotype
Erin E. Longbrake, Claudia Cantoni, Francesca Cignarella, Anne H. Cross MD, & Laura Piccio. ACTRIMS 2017.
Background: The efficacy of anti-CD20 monoclonal antibodies in clinical trials of relapsing multiple sclerosis (MS) confirmed that B-cells play an important role. Little is known about how dimethyl fumarate (DMF) affects B-cells. Objectives: To determine how the composition and function of circulating B-cell populations is affected by exposure to DMF.
Methods: Peripheral blood mononuclear cells (PBMC) and serum were collected from MS patients stably treated with DMF, patients on no immunomodulatory therapy and healthy volunteers. B-cell subpopulations were analyzed by flow cytometry.
Results: The proportions of circulating class-switched memory B-cells (CD20+ IgD- CD27+), non-class-switched memory B-cells (CD20+, IgD+ CD27+) and double negative memory B-cells (CD20+ IgD- CD27-) were significantly decreased among patients taking DMF relative to healthy and untreated MS controls. Concurrently, there was an increase in the proportion of circulating naïve B-cells (CD20+ IgD+ CD27-). Expression of the activation marker CD80 was also reduced on circulating B-cells from DMF-treated patients. Quantitative serum immunoglobulins did not change with DMF treatment.
Conclusions: DMF reduced the expression of circulating memory B-cells. A similar pattern has been observed among other disease modifying therapies, and this may underlie some of the drugs’ efficacy against relapsing MS. More study is needed to determine whether changes in B-cell phenotypic markers are paralleled by changes in B-cell function