Sistema de Salut de Catalunya
Institut Català de la Salut
[Wiendl H] Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany. [Schmierer K] The Blizard Institute, Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK. Clinical Board Medicine (Neuroscience), The Royal London Hospital, Barts Health NHS Trust, London, UK. [Hodgkinson S] Ingham Institute for Applied Medical Research, University of New South Wales Medicine, Sydney, NSW, Australia. [Derfuss T] Department of Neurology, University Hospital Basel, Basel, Switzerland. [Chan A] Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. [Sellebjerg F] Danish MS Center, Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. [Montalban X] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-02-17T13:29:10Z
2023-02-17T13:29:10Z
2023-01
Cladribina; Cèl·lules immunitàries
Cladribina; Células inmunitarias
Cladribine; Immune cells
Background and Objectives Cladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS). Methods Immunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+ B cells, CD4+ and CD8+ T cells, CD16+ natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed. Results The full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%–87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period. Discussion Cladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence.
This work was supported by the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
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Esclerosi múltiple - Tractament; Medicaments immunosupressors; DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents; ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::efectos fisiológicos de los fármacos::factores inmunitarios::inmunosupresores
Lippincott Williams & Wilkins
Neurology, Neuroimmunology and Neuroinflammation;10(1)
https://doi.org/10.1212/NXI.0000000000200048
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
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Articles científics - HVH [3396]
