Changes of cerebrospinal fluid cytokine profile as a result of switching from first line MS-therapies to rituximab

Background: New treatment strategies in multiple sclerosis provide insights not only in the clinical effects but also, by their differences in mechanisms of action, in the immunopathological mechanisms behind disease activity. Objective: This study describes the change in cyto- and chemokine profile over a two-year period in a cohort of patients with clinically stable RRMS after treatment shift from ongoing first-line injectable disease modifying therapy (iDMT), e.g. interferon beta or glatirameracetat, to the anti-CD20 depleting agent rituximab and the differences compared with a cohort of healthy controls. Method: CSF from 73 patients with clinically stable RRMS was analysed by an elektrochemiluminiscens-based ELISA for a panel of 22 cytokines before and one and two year after treatment shift to rituximab and compared with 55 healthy controls. Results: During the first year of treatment it was a significant reduction (p< 0.005) in levels of IL-6, IL-8, IL-10, IL-12, IL-15, IP-10, MCP-1, MDC, TARC, sICAM, sVCAM and a significant elevation (p< 0,005) in levels of IL-7 and MIP-1b. Compared to healthy controls it was a significantly higher (p< 0,005) level of IFN-gamma, IL-6, IL-8, IL-10, IL-12, IL-15, TNF, IP-10, MDC, MIP-1a, MIP-1b, TARC, SAA, sICAM and sVCAM in patients with RRMS before treatment shift. Levels of IL-5 and IL-7 were significantly lower. One year after treatment shift the levels of IFN-gamma, IL-6, IL-7, IL-15, MIP-1a and SAA did not differ significantly between patients with RRMS and healthy controls. Conclusion: This study demonstrates significant changes in cyto- and chemokine profile in patients with RRMS after treatment shift from iDMT to rituximab and compared with healthy controls.