title: Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis.
abstract: An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease.
  
  
  
  In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred. The primary end point was the percentage of patients with disability progression confirmed at 12 weeks in a time-to-event analysis.
  
  
  
  The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (hazard ratio, 0.76; 95% confidence interval [CI], 0.59 to 0.98; P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted magnetic resonance imaging (MRI) decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). There was no significant difference in the change in the Physical Component Summary score of the 36-Item Short-Form Health Survey. Infusion-related reactions, upper respiratory tract infections, and oral herpes infections were more frequent with ocrelizumab than with placebo. Neoplasms occurred in 2.3% of patients who received ocrelizumab and in 0.8% of patients who received placebo; there was no clinically significant difference between groups in the rates of serious adverse events and serious infections.
  
  
  
  Among patients with primary progressive multiple sclerosis, ocrelizumab was associated with lower rates of clinical and MRI progression than placebo. Extended observation is required to determine the long-term safety and efficacy of ocrelizumab. (Funded by F. Hoffmann-La Roche; ORATORIO ClinicalTrials.gov number, NCT01194570 .).
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Arnold
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Jérôme
authors.initials: J
authors.lastname: de Seze
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hemmer
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Fred
authors.initials: F
authors.lastname: Lublin
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Kottil W
authors.initials: KW
authors.lastname: Rammohan
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Selmaj
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Anthony
authors.initials: A
authors.lastname: Traboulsee
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Annette
authors.initials: A
authors.lastname: Sauter
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Donna
authors.initials: D
authors.lastname: Masterman
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Paulo
authors.initials: P
authors.lastname: Fontoura
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Hideki
authors.initials: H
authors.lastname: Garren
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Nicole
authors.initials: N
authors.lastname: Mairon
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Peter
authors.initials: P
authors.lastname: Chin
authors.affiliation: From Hospital Vall d'Hebron University, Barcelona (X.M.); University of California, San Francisco, San Francisco (S.L.H.), and Genentech, South San Francisco (D.M., H.G., P.C.) - both in California; University Hospital Basel, University of Basel (L.K.), and F. Hoffmann-La Roche (A.S., P.F., S.B., N.M.), Basel, Switzerland; McGill University (D.L.A., A.B.-O.) and NeuroRx Research (D.L.A.), Montreal, and University of British Columbia, Vancouver (A.T.) - both in Canada; University Vita-Salute San Raffaele, Milan (G.C.); University Hospital of Strasbourg, Clinical Investigation Center (INSERM Unité 1434), Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France (J.S.); Barts and the London School of Medicine and Dentistry, London (G.G.); Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf (H.-P.H.), and Technical University of Munich and Munich Cluster for Systems Neurology, Munich (B.H.) - both in Germany; Icahn School of Medicine at Mount Sinai, New York (F.L.); University of Miami, Miami (K.W.R.); Medical University of Łódź, Łódź, Poland (K.S.); and McGovern Medical School, University of Texas Health Science Center at Houston, Houston (J.S.W.).
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Wolinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018951:Antigens, CD20; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000000981:diagnostic imaging; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects; D057194:Intention to Treat Analysis; D018655:Lymphocyte Count; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000276:immunology; D013601:T-Lymphocytes; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018951:Antigens, CD20; C533411:ocrelizumab