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Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study

T. Spelman, G. Simoneau, R. Hyde, R. Kuhelj, R. Alroughani, S. Ozakbas, R. Karabudak, BI. Yamout, SJ. Khoury, M. Terzi, C. Boz, D. Horakova, E. Kubala Havrdova, B. Weinstock-Guttman, F. Patti, A. Altintas, S. Mrabet, R. Gouider, J. Inshasi, V....

Spelman, Tim
Author Spelman, Tim ORCID From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Simoneau, Gabrielle
Author Simoneau, Gabrielle From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Hyde, Robert
Author Hyde, Robert From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Kuhelj, Robert
Author Kuhelj, Robert From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Alroughani, Raed
Author Alroughani, Raed From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Ozakbas, Serkan
Author Ozakbas, Serkan From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Karabudak, Rana
Author Karabudak, Rana From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Yamout, Bassem I
Author Yamout, Bassem I From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Khoury, Samia J
Author Khoury, Samia J From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Terzi, Murat
Author Terzi, Murat From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Boz, Cavit
Author Boz, Cavit From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Horakova, Dana
Author Horakova, Dana From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Kubala Havrdova, Eva
Author Kubala Havrdova, Eva From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Weinstock-Guttman, Bianca
Author Weinstock-Guttman, Bianca ORCID From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Patti, Francesco
Author Patti, Francesco ORCID From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Altintas, Ayse
Author Altintas, Ayse From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Mrabet, Saloua
Author Mrabet, Saloua From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Gouider, Riadh
Author Gouider, Riadh ORCID From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Inshasi, Jihad
Author Inshasi, Jihad From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Shaygannejad, Vahid
Author Shaygannejad, Vahid From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Eichau, Sara
Author Eichau, Sara From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Ward, W Luke
Author Ward, W Luke From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
Butzkueven, Helmut
Author Butzkueven, Helmut ORCID From the MSBase Foundation (T.S.), Melbourne, Australia Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden Biogen (G.S.), Toronto, Ontario, Canada Biogen (R.H., Robert Kuhelj), Baar, Switzerland Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait Dokuz Eylul University (S.O.), Konak/Izmir Hacettepe University (Rana Karabudak), Ankara, Turkey Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon Mayis University (M.T.), Samsun KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia Rashid Hospital (J.I.), Dubai, United Arab Emirates Isfahan University of Medical Sciences (V.S.), Iran Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain Ashfield MedComms (W.L.W.), Middletown, CT Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia
MSBase Investigators
Author MSBase Investigators

Neurology. 2024 ; 102 (7) : e208114. [pub] 20240306

ISSN 1526-632X
Medvik
Source

Language English Country United States

Document type Journal Article

Persistent link https://www.medvik.cz/link/bmc24006516

PubMed 38447093
DOI 10.1212/wnl.0000000000208114
Knihovny.cz E-resources

MeSH
Child MeSH
Adult MeSH
Fingolimod Hydrochloride * therapeutic use MeSH
Humans MeSH
Natalizumab therapeutic use MeSH
Recurrence MeSH
Registries MeSH
Retrospective Studies MeSH
Multiple Sclerosis * drug therapy MeSH
Check Tag
Child MeSH
Adult MeSH
Humans MeSH
Publication type
Journal Article MeSH

BACKGROUND AND OBJECTIVES: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

Ashfield MedComms Middletown CT

Biogen Baar Switzerland

Biogen Toronto Ontario Canada

Department of Clinical Neuroscience Karolinska Institute Stockholm Sweden

Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia Catania Italy

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Czech Republic

Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health Razi University Hospital

Department of Neurology Box Hill Hospital Monash University Box Hill Victoria Australia

Department of Neurology Buffalo General Medical Center Buffalo NY

Department of Neurology Hospital Universitario Virgen Macarena Sevilla Spain

Department of Neurology Koc University Istanbul Turkey

Department of Neurology Razi University Hospital Tunis Tunisia

Department of Neuroscience Central Clinical School Monash University Melbourne

Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait

Dokuz Eylul University Konak Izmir

From the MSBase Foundation Melbourne Australia

Hacettepe University Ankara Turkey

Isfahan University of Medical Sciences Iran

KTU Medical Faculty Farabi Hospital Trabzon Turkey

Mayis University Samsun

Nehme and Therese Tohme Multiple Sclerosis Center American University of Beirut Medical Center Lebanon

Rashid Hospital Dubai United Arab Emirates

References provided by Crossref.org

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100 1_: $a Spelman, Tim $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia $1 https://orcid.org/0000000192043216

245 10: $a Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study / $c T. Spelman, G. Simoneau, R. Hyde, R. Kuhelj, R. Alroughani, S. Ozakbas, R. Karabudak, BI. Yamout, SJ. Khoury, M. Terzi, C. Boz, D. Horakova, E. Kubala Havrdova, B. Weinstock-Guttman, F. Patti, A. Altintas, S. Mrabet, R. Gouider, J. Inshasi, V. Shaygannejad, S. Eichau, WL. Ward, H. Butzkueven, MSBase Investigators

520 9_: $a BACKGROUND AND OBJECTIVES: Patients with pediatric-onset multiple sclerosis (POMS) typically experience higher levels of inflammation with more frequent relapses, and though patients with POMS usually recover from relapses better than adults, patients with POMS reach irreversible disability at a younger age than adult-onset patients. There have been few randomized, placebo-controlled clinical trials of multiple sclerosis (MS) disease-modifying therapies (DMTs) in patients with POMS, and most available data are based on observational studies of off-label use of DMTs approved for adults. We assessed the effectiveness of natalizumab compared with fingolimod using injectable platform therapies as a reference in pediatric patients in the global MSBase registry. METHODS: This retrospective study included patients with POMS who initiated treatment with an injectable DMT, natalizumab, or fingolimod between January 1, 2006, and May 3, 2021. Patients were matched using inverse probability treatment weighting. The primary outcome was time to first relapse from index therapy initiation. Secondary study outcomes included annualized relapse rate; proportions of relapse-free patients at 1, 2, and 5 years; time to treatment discontinuation; and times to 24-week confirmed disability worsening and confirmed disability improvement. RESULTS: A total of 1,218 patients with POMS were included in this analysis. Patients treated with fingolimod had a significantly lower risk of relapse than patients treated with injectable DMTs (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.29-0.83; p = 0.008). After adjustment for prior DMT experience in the unmatched sample, patients treated with natalizumab had a significantly lower risk of relapse than patients treated either with injectable DMTs (HR, 0.15; 95% CI 0.07-0.31; p < 0.001) or fingolimod (HR, 0.37; 95% CI 0.14-1.00; p = 0.049). The adjusted secondary study outcomes were generally consistent with the primary outcome or with previous observations. The findings in the inverse probability treatment weighting-adjusted patient populations were confirmed in multiple sensitivity analyses. DISCUSSION: Our analyses of relapse risk suggest that natalizumab is more effective than fingolimod in the control of relapses in this population with high rates of new inflammatory activity, consistent with previous studies of natalizumab and fingolimod in adult-onset patients and POMS. In addition, both fingolimod and natalizumab were more effective than first-line injectable therapies. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with POMS treated with natalizumab had a lower risk of relapse than those with fingolimod.

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700 1_: $a Simoneau, Gabrielle $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Hyde, Robert $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Kuhelj, Robert $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Alroughani, Raed $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Ozakbas, Serkan $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Karabudak, Rana $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Yamout, Bassem I $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Khoury, Samia J $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Terzi, Murat $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Boz, Cavit $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Horakova, Dana $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Kubala Havrdova, Eva $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Weinstock-Guttman, Bianca $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia $1 https://orcid.org/000000016732151X

700 1_: $a Patti, Francesco $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia $1 https://orcid.org/0000000269230846

700 1_: $a Altintas, Ayse $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Mrabet, Saloua $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Gouider, Riadh $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia $1 https://orcid.org/0000000196153797

700 1_: $a Inshasi, Jihad $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Shaygannejad, Vahid $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Eichau, Sara $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Ward, W Luke $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia

700 1_: $a Butzkueven, Helmut $u From the MSBase Foundation (T.S.), Melbourne, Australia; Department of Clinical Neuroscience (T.S.), Karolinska Institute, Stockholm, Sweden; Biogen (G.S.), Toronto, Ontario, Canada; Biogen (R.H., Robert Kuhelj), Baar, Switzerland; Division of Neurology (R.A.), Department of Medicine, Amiri Hospital, Sharq, Kuwait; Dokuz Eylul University (S.O.), Konak/Izmir; Hacettepe University (Rana Karabudak), Ankara, Turkey; Nehme and Therese Tohme Multiple Sclerosis Center (B.I.Y., S.J.K.), American University of Beirut Medical Center, Lebanon; 19 Mayis University (M.T.), Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Trabzon, Turkey; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), First Faculty of Medicine, Charles University in Prague and General University Hospital, Czech Republic; Department of Neurology (B.W.-G.), Buffalo General Medical Center, Buffalo, NY; Department of Medical and Surgical Sciences and Advanced Technologies (F.P.), GF Ingrassia, Catania, Italy; Department of Neurology (A.A.), School of Medicine and Koc University Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey; Department of Neurology and Clinical Investigation Center Neurosciences and Mental Health (S.M.), Razi University Hospital; Department of Neurology (R.G.), Razi University Hospital, Tunis, Tunisia; Rashid Hospital (J.I.), Dubai, United Arab Emirates; Isfahan University of Medical Sciences (V.S.), Iran; Department of Neurology (S.E.), Hospital Universitario Virgen Macarena, Sevilla, Spain; Ashfield MedComms (W.L.W.), Middletown, CT; Department of Neuroscience (H.B.), Central Clinical School, Monash University, Melbourne; and Department of Neurology (H.B.), Box Hill Hospital, Monash University, Box Hill, Victoria, Australia $1 https://orcid.org/0000000339408727

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Comparative Effectiveness of Natalizumab, Fingolimod, and Injectable Therapies in Pediatric-Onset Multiple Sclerosis: A Registry-Based Study

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