Interim Results of an Open-Label Study to Assess the Effects of Delayed-release Dimethyl Fumarate on Lymphocyte Subsets and Immunoglobulins in Patients with Relapsing-remitting Multiple Sclerosis (P5.380)

Objective: Given the immunomodulatory properties of delayed-release dimethyl fumarate (DMF) and its observed effects on lymphocytes, further research evaluating these effects is needed. We are conducting this study to comprehensively characterize the effects of DMF on circulating lymphocyte subsets and immunoglobulin levels within the first year of treatment and beyond. Background: DMF is an approved oral disease-modifying therapy (DMT) to treat RRMS. DMF has putative immunomodulatory properties through activation of the Nrf2-dependent and NRF2-independent pathways. A mean ALC decrease by ~30% during the first year of treatment has been observed in pivotal trials and in real-world settings; however, a detailed and comprehensive analysis of the impact and time course of changes in circulating lymphocyte subsets has not been described. Design/Methods: In this ongoing, open-label, multicenter study, 218 patients aged 18–65 years with RRMS were enrolled and treated with DMF 240mg twice daily. Blood samples were taken at baseline, and at Weeks 4, 8, 12, 24, 36, and 48. Lymphocyte subset changes were monitored by flow cytometry using a comprehensive panel of surface markers and intracellular cytokines. Results: This interim analysis includes ~165 patients from 6 different countries with ≥6 months follow-up or who discontinued the study earlier. The overall safety results and the changes in ALC and detailed lymphocyte subset counts, including phenotypic characterization of CD4 + T-cell, CD8 + T-cell, B-cell, and natural killer cell subsets, based on a comprehensive panel of surface markers and intracellular cytokines will be presented. Conclusions: The results will provide insight into the effects of DMF on a comprehensive panel of immune cell subsets and their correlation with changes in ALC within the first 6 months of treatment initiation and may help to understand treatment-related changes in immune cell function. Study Supported by: Biogen Disclosure: Dr. Von Hehn has received personal compensation for activities with Biogen as an employee. Dr. Mehta has received personal compensation for activities with Biogen as an employee. Dr. Mehta holds stock and/or stock options in Biogen. Dr. Prada has received personal compensation for activities with Biogen as an employee. Dr. Prada holds stock and/or stock options in Biogen. Dr. Yang has received personal compensation for activities with Biogen as an employee. Dr. Yang hold stocks and/or stock options in Biogen. Dr. Liu has received personal compensation for activities with Biogen as an employee. Dr. Ray has received personal compensation for activities with Biogen Idec. Dr. Ray holds stock and/or stock options in Biogen Idec. Dr. Sheikh has received personal compensation for activities with Biogen as an employee. Dr. Sheikh holds stock and/or stock options in Biogen.