Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity. (May 2021)

• Record Type: Journal Article
• Authors: Longbrake, Erin E; Mao-Draayer, Yang; Cascione, Mark; Zielinski, Tomasz; Bame, Eris; Brassat, David; Chen, Chongshu; Kapadia, Shivani; Mendoza, Jason P; Miller, Catherine; Parks, Becky; Xing, Diana; Robertson, Derrick
• Is Part Of: Multiple sclerosis. Volume 27:Number 6(2021)
• Page Start: 883
• Page End: 894
• Publication Date: 2021-05
• Subjects: Delayed-release dimethyl fumarate -- multiple sclerosis -- lymphocytes -- B cells -- immunoglobulin; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458520937282
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Delayed-release dimethyl fumarate (DMF) demonstrates sustained efficacy and safety for relapsing forms of MS. Absolute lymphocyte count (ALC) is reduced initially, then stabilizes on treatment. Objective: PROCLAIM, a 96-week, prospective, open-label, phase 3b study, assessed lymphocyte subsets and immunoglobulin (Ig) levels during 48 and 96 weeks (W) of DMF treatment. Methods: Patients received 240 mg DMF BID. Endpoints: lymphocyte subset count changes (primary); Ig isotypes and ALC changes (secondary); adverse events and relationship between ALC changes and ARR/EDSS (exploratory); and neurofilament assessment (ad hoc). Results: Of 218 patients enrolled, 158 (72%) completed the study. Median ALC decreased 39% from baseline to W96 (BL–W96), stabilizing above the lower limit of normal (baseline: 1.82 × 10 9 /L; W48: 1.06 × 10 9 /L; W96: 1.05 × 10 9 /L). CD4 + and CD8 + T cells correlated highly with ALC from BL–W96 ( p < 0.001). Relative to total T cells, naive CD4 + and CD8 + T cells increased, whereas CD4 + and CD8 + central and effector memory T cells decreased. Total IgA, IgG, IgM, and IgG1–4 subclass levels remained stable. Adverse event rates were similar across ALC subgroups. ARR, EDSS, and neurofilament were not correlated with ALCs. Conclusion: Lymphocyte decreases with DMF were maintained over treatment, yet immunoglobulins remained stable. No increase in infection incidence was observed in patients with or without lymphopenia. Support: Biogen