Evidence map›Paper›PMID 39969782›Full record

ArticleAdvances in therapy2025

LymphoTEC: a Retrospective Real-World Study on Lymphocyte Reconstitution After Lymphopenia in Patients with Multiple Sclerosis Treated with Dimethyl Fumarate in France.

Jérôme de Sèze, Pierre Labauge, Roland Liblau, Mikel Martinez, Thibault Moreau, Laurent Suchet, Patrick Vermersch, Sandra Vukusic, Guillaume Mathey, Laure Michel and 30 more

Registry-linked trialAbstract readMulticenter Study
In one paragraph

Article in Advances in therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04756687 (A Retrospective Analysis in Real World on Lymphocyte Reconstitution After Lymphopenia in Patients Treated by Tecfidera and Description of Management Strategies in France), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

NCT04756687 completednot on this map

A Retrospective Analysis in Real World on Lymphocyte Reconstitution After Lymphopenia in Patients Treated by Tecfidera and Description of Management Strategies in France

TypeobservationalSponsorBiogenRan2021 to 2021Enrolled1,507ConditionsMultiple Sclerosis, Multiple Sclerosis, Relapsing-RemittingArmsDimethyl fumarate
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors.

Jérôme de SèzeService de Neurologie et Centre d'Investigation Clinique, CHU de Strasbourg, INSERM 1434, Strasbourg, France. Jerome.DESEZE@chru-strasbourg.fr.ORCID 0000-0002-7197-7578
Pierre LabaugeService de Neurologie, CHU de Montpellier, 34295, Montpellier Cedex 5, France.
Roland LiblauToulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, Institut National de la Santé et de la Recherche Médicale (INSERM), UPS, Toulouse, France.
Mikel MartinezCH de Dax, Dax, France.
Thibault MoreauService de Neurologie, CHU de Dijon, Dijon, France.
Laurent SuchetDepartment of Neurology, Hôpital Européen de Marseille, Marseille, France.
Patrick VermerschUniv. Lille, INSERM U1172 LilNCog, CHU Lille, FHU Precise, Lille, France.
Sandra VukusicHospices Civils de Lyon, Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, 69677, Bron, France.
Guillaume MatheyNancy University Hospital, Department of Neurology, Nancy, France.
Laure MichelNeurology Department, Clinical Neuroscience Centre, CIC_P1414 INSERM, Rennes, University Hospital, Rennes University, Rennes, France.
Jonathan CironCHU de Toulouse, CRC-SEP, Department of Neurology, 31059, Toulouse Cedex 9, France.
Aurelie RuetDepartment of Neurology, University Hospital of Bordeaux, 33076, Bordeaux, France.
Elisabeth MaillartDépartement de Neurologie, Hôpital Pitié-Salpêtrière, APHP, Paris, France.
Helene ZephirCHU Lille, CRC-SEP Lille, Univ Lille, U1172, 59000, Lille, France.
Caroline PapeixFondation Rotschild, Department of Neurology, 75000, Paris, France.
Gilles DeferCHU de Caen, MS Expert Centre, Department of Neurology, Normandy University, 14033, Caen, France.
Mikael CohenNeurology, UR2CA_URRIS, Centre Hospitalier Universitaire Pasteur 2, Université Nice Côte d'Azur, Nice, France.
David Axel LaplaudNantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CIC INSERM 1413, Service de Neurologie, 44000, Nantes, France.
Eric BergerCHU de Besançon, Service de Neurologie, 25030, Besançon, France.
Pierre ClavelouCHU Clermont-Ferrand, Department of Neurology, 63000, Clermont-Ferrand, France.
Eric ThouvenotDepartment of Neurology, Nimes University Hospital, 30029, Nimes Cedex 9, France.
Olivier HeinzlefHôpital de Poissy, Department of Neurology, 78300, Poissy, France.
Jean PelletierAix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France.
Claire GiannesiniSorbonne Université; Department of Neurology, AP-HP, Saint-Antoine Hospital, 75000, Paris, France.
Olivier CasezCHU Grenoble Alpes, Department of Neurology, Neurology MS Clinic Grenoble, Grenoble Alpes University Hospital, Grenoble, 38700, La Tronche, France.
Bertrand BourreCHU de Rouen, Department of Neurology, 76000, Rouen, France.
Abir WahabAPHP, Hôpital Henri Mondor, Department of Neurology, 94000, Créteil, France.
Laurent MagyCHU de Limoges, Hôpital Dupuytren, Department of Neurology, 87000, Limoges, France.
Jean-Philippe CamdessanchéCHU de Saint-Étienne, Hôpital Nord, Department of Neurology, 42000, Saint-Étienne, France.
Inès DoghriCHU de Tours, Hôpital Bretonneau, CRC-SEP and Department of Neurology, 37000, Tours, France.
Céline LabeyrieCHU Bicêtre, Department of Neurology, 94275, Le Kremlin Bicêtre, France.
Karolina HankiewiczDepartment of Neurology, Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, 93200, Saint-Denis, France.
Jean-Philippe NeauCHU La Milétrie, Hôpital Jean Bernard, Department of Neurology, 86000, Poitiers, France.
Corinne PottierCH de Pontoise, Hôpital René Dubos, Department of Neurology, 95300, Pontoise, France.
Pamela DobayBiogen International GmbH, Baar, Switzerland.
Hanyue LiPreviously: Biogen, Cambridge, MA, USA.
Seth LevinBiogen, Cambridge, MA, USA.
Marilyn GrosBiogen France, 92400, Courbevoie, France.ORCID 0000-0002-8076-4777
Marta RuizBiogen France, 92400, Courbevoie, France.ORCID 0009-0007-7744-4207
Fabien RollotUniversité de Lyon, Université Claude Bernard Lyon 1, 69000, Lyon, France.

Funding

Agence Nationale de la Recherche ANR-10-COHO-002
6 · The paper itself

Abstract

introductionDimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Some patients may develop lymphopenia on DMF; therefore, LymphoTEC evaluated absolute lymphocyte count (ALC) reconstitution after DMF discontinuation.

methodsLymphoTEC was a retrospective, multicenter study of patients with RRMS in the Observatoire Français de la Sclérose en Plaques registry. Times to ALC reconstitution and lymphopenia were estimated by the Kaplan-Meier method. Univariate and multivariate analyses evaluated factors associated with ALC reconstitution after DMF discontinuation or lymphopenia after DMF initiation. Patients treated with DMF for ≥ 3 months with ≥ 1 ALC in the 6 months before/close to DMF initiation and ≥ 1 ALC during treatment were included.

resultsOverall, 1429 RRMS patients were included; 356 patients developed lymphopenia, of whom 183 discontinued DMF. Overall, ALC decreased by 33% over the first year and plateaued thereafter. The probability of developing lymphopenia was 18.2% after 1 year. In patients with lymphopenia, median times to ALC reconstitution after DMF discontinuation were 3.8 months overall, 4.0 months for Grade 1 lymphopenia, 3.0 months for Grade 2, and 9.7 months for Grade 3. At 12 months, 83.0% had reconstituted ALC. In DMF discontinuers, median time to discontinuation was 1.2 years. There was no increased risk of serious or opportunistic infections in patients with lymphopenia. No cases of progressive multifocal leukoencephalopathy were reported. First ALC reconstitution after DMF discontinuation was associated with diabetes, DMF duration, DMF duration before lymphopenia, and DMF duration after lymphopenia; first lymphopenia after DMF initiation was associated with age and ALC at DMF initiation.

conclusionLymphoTEC confirms previous reports on DMF-induced lymphopenia; the benefit-risk profile of DMF remains favorable. Most cases of lymphopenia were not severe and ALC reconstitution typically occurred within 4 months of DMF discontinuation. Patients with shorter and milder lymphopenia had faster ALC reconstitution.

trial registrationClinicalTrials.gov NCT04756687.

Indexed as

Dimethyl FumarateImmunosuppressive AgentsLymphopeniaMultiple Sclerosis, Relapsing-RemittingAdultFemaleFranceHumansLymphocyte CountMaleMiddle AgedRetrospective StudiesDimethyl FumarateImmunosuppressive AgentsDimethyl fumarateLymphocyte reconstitutionLymphopeniaReal-world dataRelapsing–remitting multiple sclerosis

Identifiers

PMID39969782
PMCPMC11929680

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.