ArticleNeurology2019
Effect of dimethyl fumarate on lymphocytes in RRMS: Implications for clinical practice.
4 registry-linked trialsOpen access · hybridAbstract read
In one paragraph
Article in Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 44 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 3 pooled it
8.8field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Double-Blind, Placebo-Controlled, Dose-Ranging Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis
Who cites it
44 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Drug-Induced Progressive Multifocal Leukoencephalopathy (PML): A Systematic Review and Meta-Analysis.Drug safety · 2024Pooled it
- Risk of COVID-19 infection and severe disease in MS patients on different disease-modifying therapies.Multiple sclerosis and related disorders · 2022Pooled it
- COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review.Multiple sclerosis and related disorders · 2021Pooled it
- Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients.Advances in therapy · 2025Trial
- Lymphocyte count polygenicity underlies dimethyl fumarate-associated lymphopenia in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Article
- T cell-mediated immunodysregulation in multiple sclerosis: from pathogenic subsets to therapeutic advances.Frontiers in immunology · 2026Review
- LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France.Advances in therapy · 2025Article
- Blood-Brain Barrier Disruption in Neuroimmunological Disease.International journal of molecular sciences · 2024Review
- Frequency of Dimethyl Fumarate-Induced Lymphopenia among Omani Patients with Multiple Sclerosis.Sultan Qaboos University medical journal · 2024Article
- Era of COVID-19 in Multiple Sclerosis Care.Neurologic clinics · 2024Review
- Case report: Primary cytomegalovirus infection in a patient with late onset multiple sclerosis treated with dimethyl fumarate.Frontiers in neurology · 2024Article
- Article
- Beyond Antioxidation: Keap1-Nrf2 in the Development and Effector Functions of Adaptive Immune Cells.ImmunoHorizons · 2023Review
- Multiple Sclerosis Management During the COVID-19 Pandemic.Current neurology and neuroscience reports · 2022Review
- Dimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation.EJNMMI research · 2022Article
- Association of Disease-Modifying Therapies with COVID-19 Susceptibility and Severity in Patients with Multiple Sclerosis: A Systematic Review and Network Meta-Analysis.Multiple sclerosis international · 2022Review
- Review
- Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis.Neurology · 2021Article
- Secondary Immunodeficiency and Risk of Infection Following Immune Therapies in Neurology.CNS drugs · 2021Review
- CMV meningitis associated with dimethyl fumarate therapy-induced lymphopenia in a multiple sclerosis patient.Journal of neurology · 2021Article
Corrections and comments
- Commented on by
Authors and funding
17 authors at 2 institutions in 2 countries.
Devangi MehtaFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT. devangi.mehta@biogen.com catherine.miller@biogen.com.
Catherine MillerFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT. devangi.mehta@biogen.com catherine.miller@biogen.com.
Douglas L ArnoldFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Eris BameFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Amit Bar-OrFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Ralf GoldFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Jerome HannaFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Ludwig KapposFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Shifang LiuFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
André MattaFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
J Theodore PhillipsFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Derrick RobertsonFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Christian A von HehnFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Jordana CampbellFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Karen SpachFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Lili YangFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
Robert J FoxFrom Biogen (D.M., C.M., E.B., J.H., S.L., A.M., C.A.v.H., L.Y.), Cambridge, MA; NeuroRx Research (D.L.A.), Montreal; Montreal Neurological Institute (D.L.A.), McGill University, Montreal, Canada; Center for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), Perelman School of Medicine, University of Pennsylvania, Philadelphia; Department of Neurology (R.G.), St. Josef Hospital, Ruhr University, Bochum, Germany; Department of Neurology (L.K.), University Hospital Basel, Switzerland; University of New Mexico Health Sciences Center (J.T.P.), Albuquerque; Department of Neurology, Multiple Sclerosis Division (D.R.), Morsani College of Medicine, University of South Florida, Tampa; Mellen Center for Multiple Sclerosis, Neurological Institute (R.J.F.), Cleveland Clinic, OH; Envision Pharma Group (J.C.), Sydney, Australia; and Envision Pharma Group (K.S.), Southport, CT.
St. Josef-Hospital · DEUniversity of South Florida · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo assess functional changes in lymphocyte repertoire and subsequent clinical implications during delayed-release dimethyl fumarate (DMF) treatment in patients with multiple sclerosis.
methodsUsing 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.
resultsIn 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.
conclusionsDMF shifted the immunophenotype of circulating lymphocyte subsets. ALCs were closely correlated with CD4 TRIAL REGISTRATION NUMBERS: EUDRA CT 2015-001973-42, NCT00168701, NCT00420212, NCT00451451, and NCT00835770.
Indexed as
AdultB-LymphocytesCD4-CD8 RatioCross-Sectional StudiesDelayed-Action PreparationsDimethyl FumarateFemaleHumansImmunosuppressive AgentsLongitudinal StudiesLymphocyte CountLymphocytesLymphopeniaMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingDelayed-Action PreparationsDimethyl FumarateImmunosuppressive Agents
Identifiers
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LicenceCC BY-NC-ND
Read underepoch 390
Registered trials
NCT00168701ClinicalTrials.gov
NCT00420212ClinicalTrials.gov
NCT00451451ClinicalTrials.gov
NCT00835770ClinicalTrials.gov
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