January 2023; 10 (1) Research ArticleOpen Access
Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets
A MAGNIFY-MS Substudy
Heinz Wiendl, Klaus Schmierer, Suzanne Hodgkinson, Tobias Derfuss, Andrew Chan, Finn Sellebjerg, Anat Achiron, Xavier Montalban, Alexandre Prat, Nicola De Stefano, Frederik Barkhof, Letizia Leocani, Patrick Vermersch, Anita Chudecka, Claire Mwape, Kristina H. Holmberg, Ursula Boschert, Sanjeev Roy; on behalf of MAGNIFY-MS Study Group
First published November 21, 2022, DOI: https://doi.org/10.1212/NXI.0000000000200048
Heinz Wiendl
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Klaus Schmierer
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Suzanne Hodgkinson
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Tobias Derfuss
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Andrew Chan
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Finn Sellebjerg
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Anat Achiron
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Xavier Montalban
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Alexandre Prat
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Nicola De Stefano
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Frederik Barkhof
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Letizia Leocani
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Patrick Vermersch
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Anita Chudecka
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Claire Mwape
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Kristina H. Holmberg
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Ursula Boschert
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Sanjeev Roy
From the Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany and Brain and Mind Center, University of Sydney, Australia; The Blizard Institute (K.S.), Centre for Neuroscience, Surgery & Trauma, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, UK; Clinical Board Medicine (Neuroscience) (K.S.), The Royal London Hospital, Barts Health NHS Trust, UK; Ingham Institute for Applied Medical Research (S.H.), University of New South Wales Medicine, Sydney, Australia; Department of Neurology (T.D.), University Hospital Basel, Switzerland; Department of Neurology (Andrew Chan), Inselspital, Bern University Hospital, University of Bern, Switzerland; Danish MS Center (F.S.), Department of Neurology, Copenhagen University Hospital–Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine (F.S.), University of Copenhagen, Denmark; Multiple Sclerosis Center (A.A.), Sheba Academic Medical Center, Ramat Gan, Israel; Sackler School of Medicine (A.A.), Tel-Aviv University, Israel; Department of Neurology-Neuroimmunology (X.M.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Hospital Universitari Vall d'Hebron, Universitat Autonoma de Barcelona, Spain; Department of Neurosciences and CRCHUM (A.P.), Université de Montréal, QC, Canada; Department of Neurological and Behavioural Sciences (N.D.S.), University of Siena, Italy; Department of Radiology (F.B.), VU University Medical Center, Amsterdam, The Netherlands; UCL Institute of Neurology (F.B.), London, UK; Experimental Neurophysiology Unit (L.L.), Vita-Salute San Raffaele University, Milan, Italy; Univ. Lille (P.V.), Inserm U1172 LilNCog, CHU Lille, FHU Precise, France; Cytel Inc (Anita Chudecka), Geneva, Switzerland; InScience Communications (C.M.), Springer Healthcare Ltd, Chester, UK; EMD Serono (K.H.H.), Billerica, MA; and Ares Trading SA (U.B., S.R.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany.
Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets
A MAGNIFY-MS Substudy
Heinz Wiendl, Klaus Schmierer, Suzanne Hodgkinson, Tobias Derfuss, Andrew Chan, Finn Sellebjerg, Anat Achiron, Xavier Montalban, Alexandre Prat, Nicola De Stefano, Frederik Barkhof, Letizia Leocani, Patrick Vermersch, Anita Chudecka, Claire Mwape, Kristina H. Holmberg, Ursula Boschert, Sanjeev Roy
Neurol Neuroimmunol Neuroinflamm Jan 2023, 10 (1) e200048; DOI: 10.1212/NXI.0000000000200048
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- Figure 1 Median Percentage Change From Baseline of B-Cell and T-Cell Subtypes
CM = central memory; EffM = effector memory; NK = natural killer; TEMRA = terminally differentiated effector memory RA+; Th = T helper.
- Figure 2 Median Values of CD19+ and CD20+ B Cell, CD4+ and CD8+ T Cell, and CD16+/CD56+ Natural Killer (NK) Cell Counts Where Additional Immunophenotyping Was Performed at Months 1 and 2, in Patients Treated With Cladribine Tablets
The first treatment course of cladribine tablets was administered at baseline and month 1. Data for CD19+ and CD20+ B cells have been slightly offset at each time point to improve readability as data points are overlapping. BL = baseline; Q = quartile.
- Figure 3 Median Values of B-Cell and T-Cell Counts in Patients Treated With Cladribine Tablets
The first treatment course of cladribine tablets was administered at baseline and month 1. BL = baseline; Q = quartile; TEMRA = terminally differentiated effector memory RA+; Th = T helper.
- Figure 4 Median Values of Natural Killer (NK) Cell Counts in Patients Treated With Cladribine Tablets
The first treatment course of cladribine tablets was administered at baseline and month 1. BL = baseline; Q = quartile.
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