Admittedly, when fingolimod hit the shelves it was all about the first oral treatment in MS.
We had a lot to learn about T cells and just heard of the B cells. The therapeutic era of the time was definitely not about finessing Multiple Sclerosis.
Fingolimod like other immunomodulatory therapies preceding it was crude in its end results, but effective nonetheless.
It is therefore with interest that I read the communication that not only does fingolimod drop circulating lymphocyte numbers, it also reduces the interaction between T cells, B cells and other antigen presenting cells, as a consequence of the first. Without trying to it modulates the pro-inflammatory IL-31/soluble CD40L axis (see Figure below), crippling the co-stimulatory role played activated T-helper CD4+ lymphocytes with other partner cells.
One might argue that more finesse is needed for the sake of selectivity, but to achieve the same effect?
J Neuroimmunol. 2020 Nov 5;350:577435. doi: 10.1016/j.jneuroim.2020.577435. Online ahead of print.
Correlation between IL-31 and sCD40L plasma levels in Fingolimod-treated patients with Relapsing-Remitting Multiple Sclerosis (RRMS)
Marcus Vinícius Magno Gonçalves , Wesley Nogueira Brandão, Carla Longo , Jean Pierre Schatzmann Peron , Giordani Rodrigues Dos Passos , Gabriela Löw Pagliarini , Osvaldo Jose Moreira do Nascimento , Daniel Rodrigo Marinowic , Denise Cantarelli Machado , Jefferson Becker
Introduction: Multiple Sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Currently, several protocols are described for the different phases of MS. In this longitudinal study, we aim to quantify the concentration of plasma cytokines of MS patients treated with Fingolimod alone or after Glatiramer Acetate (GA) or Interferon-beta (IFN-β), in order to compeer both treatments and describes if it is possible to use them as biomarkers.
Objective: Compare the two different types of drug treatment and describes possible immune biomarkers in RRMS patients treated with Fingolimod alone or after GA or IFN-β.
Materials and methods: This is a controlled, non-randomized clinical trial. Plasma concentrations of IL-31, sCD40L and nine others cytokines were evaluated in two groups of patients with a one-year follow-up. Group 1 (n = 12): RRMS patients treated with GA or IFN-β for at least six months before the study who changed therapy to Fingolimod after six months, and Group 2 (n = 12): naïve RRMS patients who started treatment with Fingolimod. We used ANOVA two-way to analyze the cytokines and Spearman coefficient to evaluate the correlation.
Results: Although Group 2 started with a greater number of relapses per disease duration, Fingolimod treatment was effective in decreasing this parameter, as well as EDSS over 12 months. However, the treatment with GA or IFN-β on Group 1 showed a tendency to increase the number of relapses after 6 months of follow-up, which decrease when the therapy was changed to Fingolimod. After the evaluation of 11 cytokines in one year, we found that IL-31 and sCD40L were the biomarkers that demonstrated a more difference when compared to the classical ones, following the clinical pattern over the treatment period.
Conclusions: Our study describes the existence of two promising plasmatic biomarkers (IL-31 and sCD40L), which reduced plasmatic levels in RRMS patients followed the treatment time of Fingolimod, despite that more studies are needed to prove their efficiency.