title: Switching from natalizumab to fingolimod: A randomized, placebo-controlled study in RRMS.
abstract: OBJECTIVE
  To investigate the effect of different natalizumab washout (WO) periods on recurrence of MRI and clinical disease activity in patients switching from natalizumab to fingolimod.
  
  
  METHODS
  In this multicenter, double-blind, placebo-controlled trial (TOFINGO), patients with relapsing-remitting multiple sclerosis (RRMS) were randomized 1:1:1 to 8-, 12-, or 16-week WO followed by fingolimod treatment over 32 weeks from last natalizumab infusion (LNI). Brain MRI was performed at baseline and weeks 8, 12, 16, 20, and 24.
  
  
  RESULTS
  Of 142 enrolled and randomized patients, 112 (78.9%) completed the study (8 weeks, n = 41/50; 12 weeks, n = 31/42; 16 weeks, n = 40/50). Number (95% confidence interval [CI]) of active (new/newly enlarged T2) lesions from LNI through 8 weeks of fingolimod treatment (primary outcome) was similar in the 8-week (2.1 [1.7-2.6]) and 12-week WO groups (1.7 [1.3-2.2]) and higher in the 16-week WO group (8.2 [7.3-9.1]). During the WO period only, the number (95% CI) of active lesions increased with increasing WO duration (8 weeks, 0.4 [0.2-0.6]; 12 weeks, 2.1 [1.6-2.6]; 16 weeks, 3.6 [3.0-4.2]). Over the 24 weeks from LNI, gadolinium-enhancing T1 lesion counts were lower in the 8-week WO group (14.1 [5.67-22.53]) than in the 12-week (21.3 [1.41-41.19]) or 16-week (18.5 [8.40-28.60]) WO groups. More patients were relapse-free in the 8-week (88%) and 12-week (91%) WO groups than the 16-week WO group (84%). Sixty-eight percent of patients experienced adverse events (mostly mild/moderate), with similar incidence across groups. No unusually severe relapses or opportunistic infections occurred.
  
  
  CONCLUSIONS
  Initiating fingolimod therapy 8-12 weeks after natalizumab discontinuation is associated with a lower risk of MRI and clinical disease reactivation than initiation after 16-week WO.
  
  
  METHODS
  This study provides Class II evidence that for patients with RRMS switching from natalizumab to fingolimod, shorter natalizumab WO periods are associated with less MRI disease activity than are longer WO periods.
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ. lkappos@uhbs.ch.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Ernst-Wilhelm
authors.initials: EW
authors.lastname: Radue
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Tobias
authors.initials: T
authors.lastname: Derfuss
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Naegelin
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Till
authors.initials: T
authors.lastname: Sprenger
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mueller-Lenke
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Sarah
authors.initials: S
authors.lastname: Griffiths
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Rosenstiel
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gottschalk
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Frank
authors.initials: F
authors.lastname: Dahlke
authors.affiliation: From Neurology, the Departments of Medicine, Clinical Research and Biomedicine (L.K., T.D., Y.N., T.S.), the Medical Image Analysis Center (MIAC) (E.-W.R., T.S., N.M.-L.), and the Department of Radiology, Division of Neuroradiology (T.S.), University Hospital, University of Basel, Switzerland; the Department of Neuroscience (G.C.), Scientific Institute H. San Raffaele, University of Milan, Italy; Vall d'Hebron University Hospital (X.M.), Barcelona, Spain; Royal Melbourne Hospital (H.B.), Parkville, Australia; the Department of Neurology (H.W.), University of Münster, Germany; the Neuroscience and Trauma Centre (G.G.), Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK; the Department of Neurology (H.-P.H.), Heinrich Heine University, Düsseldorf, Germany; Oxford PharmaGenesis Ltd. (S.G.), Tubney Warren Barns, Oxford, UK; Novartis Pharma AG (P.v.R., Y.Z., F.D., D.T.), Basel, Switzerland; and Novartis Pharmaceutical Corporation (R.G.), East Hanover, NJ.
authors.forename: Davorka
authors.initials: D
authors.lastname: Tomic
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D057915:Drug Substitution / Q000379:methods; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D000069442:Natalizumab; D011409:Propylene Glycols / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine