DOI: 10.5061/dryad.n0cg254
title: Data from: Effect of dimethyl fumarate on lymphocytes in RRMS: implications for clinical practice

description: Objective: To assess functional changes in lymphocyte repertoire and
 subsequent clinical implications during delayed-release dimethyl fumarate
 (DMF) treatment in patients with multiple sclerosis. Methods: Using
 peripheral blood from several clinical trials of DMF, immune cell subsets
 were quantified using flow cytometry. For some patients, lymphocyte counts
 were assessed after DMF discontinuation. Incidence of adverse events,
 including serious and opportunistic infections, was assessed. Results: In
 DMF-treated patients, absolute lymphocyte counts (ALCs) demonstrated a
 pattern of decline followed by stabilization, which also was reflected in
 the global reduction in numbers of circulating functional lymphocyte
 subsets. The relative frequencies of circulating memory T- and B-cell
 populations declined and naive cells increased. No increased incidence of
 serious infection or malignancy was observed for patients treated with
 DMF, even when stratified by ALC or T-cell subset frequencies. For
 patients who discontinued DMF due to lymphopenia, ALCs increased after DMF
 discontinuation; recovery time varied by ALC level at discontinuation.
 T-cell subsets closely correlated with ALCs in both longitudinal and
 cross-sectional analyses. Conclusions: DMF shifted the immunophenotype of
 circulating lymphocyte subsets. ALCs were closely correlated with CD4+ and
 CD8+ T-cell counts, indicating that lymphocyte subset monitoring is not
 required for safety vigilance. No increased risk of serious infection was
 observed in patients with low T-cell subset counts. Monitoring ALC remains
 the most effective way of identifying patients at risk of subsequently
 developing prolonged moderate to severe lymphopenia, a risk factor for
 progressive multifocal leukoencephalopathy in DMF-treated patients. Trial
 registration numbers: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212,
 NCT00451451, and NCT00835770
description: Supplementary Table e-1
 Flow cytometry cell surface markers to phenotype cell
 typesFlow cytometry cell
 surface markers to phenotype cell typesSupplementary Table e-1
 v3.docxSupplementary Table e-2
 Multiparameter flow cytometry immunophenotyping panelsMultiparameter flow
 cytometry immunophenotyping panelsSupplementary Table e-2
 v3.docxSupplemental Table e-3
 Major lymphocyte subsets by ALC category in the long-term ENDORSE
 integrated analysisMajor lymphocyte subsets
 by ALC category in the long-term ENDORSE integrated
 analysisSupplemental Table e-3
 v3.docxSupplemental Table e-4
 Mean absolute counts of Ig antibodies from baseline to week 24
 (PROCLAIM)Mean absolute counts of
 Ig antibodies from baseline to week 24 (PROCLAIM)Supplemental Table e-4
 v3.docxSupp Figure e-1 Mean
 levels of Ig antibodies at baseline through week 24
 (PROCLAIM)Mean levels of Ig
 antibodies at baseline through week 24 (PROCLAIM)Mehta Lymphocyte Research Supp
 fig_e-1 v3.pdfSupp Figure e-2
 Lymphocytes and subsets in individual patients after DMF
 discontinuationLymphocytes and subsets
 in individual patients after DMF discontinuationMehta Lymphocyte Research Supp
 fig_e-2 v3.pdf