Skip to main content
Advertisement
  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center

Advanced Search

Main menu

  • Neurology.org
  • Journals
    • Neurology
    • Clinical Practice
    • Education
    • Genetics
    • Neuroimmunology & Neuroinflammation
  • Online Sections
    • Neurology Video Journal Club
    • Diversity, Equity, & Inclusion (DEI)
    • Neurology: Clinical Practice Accelerator
    • Practice Buzz
    • Practice Current
    • Residents & Fellows
    • Without Borders
  • Collections
    • COVID-19
    • Disputes & Debates
    • Health Disparities
    • Infographics
    • Neurology Future Forecasting Series
    • Null Hypothesis
    • Patient Pages
    • Topics A-Z
    • Translations
  • Podcast
  • CME
  • About
    • About the Journals
    • Contact Us
    • Editorial Board
  • Authors
    • Submit New Manuscript
    • Submit Revised Manuscript
    • Author Center
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

User menu

  • Subscribe
  • My Alerts
  • Log in

Search

  • Advanced search
Neurology
Home
The most widely read and highly cited peer-reviewed neurology journal
  • Subscribe
  • My Alerts
  • Log in
Site Logo
  • Home
  • Latest Articles
  • Current Issue
  • Past Issues
  • Neurology Video Journal Club
  • Residents & Fellows

Share

August 25, 2020; 95 (8) Article

A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis

Gavin Giovannoni, Volker Knappertz, Joshua R. Steinerman, Aaron P. Tansy, Thomas Li, Stephen Krieger, View ORCID ProfileAntonio Uccelli, Bernard M.J. Uitdehaag, Xavier Montalban, Hans-Peter Hartung, Maria Pia Sormani, Bruce A.C. Cree, Fred Lublin, View ORCID ProfileFrederik Barkhof
First published July 10, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010284
Gavin Giovannoni
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Volker Knappertz
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joshua R. Steinerman
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aaron P. Tansy
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas Li
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen Krieger
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antonio Uccelli
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Antonio Uccelli
Bernard M.J. Uitdehaag
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xavier Montalban
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hans-Peter Hartung
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria Pia Sormani
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruce A.C. Cree
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fred Lublin
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frederik Barkhof
From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology–Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Frederik Barkhof
Full PDF
Short Form
Citation
A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis
Gavin Giovannoni, Volker Knappertz, Joshua R. Steinerman, Aaron P. Tansy, Thomas Li, Stephen Krieger, Antonio Uccelli, Bernard M.J. Uitdehaag, Xavier Montalban, Hans-Peter Hartung, Maria Pia Sormani, Bruce A.C. Cree, Fred Lublin, Frederik Barkhof
Neurology Aug 2020, 95 (8) e1027-e1040; DOI: 10.1212/WNL.0000000000010284

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Permissions

Make Comment

See Comments

Downloads
251

Share

  • Article
  • Figures & Data
  • Info & Disclosures
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Objective To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS).

Methods In the randomized, double-blind, placebo-controlled, phase 2 study, ARPEGGIO (A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes), eligible patients with PPMS were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.5 mg or matching placebo. Percentage brain volume change (PBVC; primary endpoint) from baseline to week 48 was assessed by MRI. Secondary and exploratory endpoints included clinical and MRI measures. Efficacy endpoints were evaluated using a predefined, hierarchical statistical testing procedure. Safety was monitored throughout the study. The laquinimod 1.5 mg dose arm was discontinued on January 1, 2016, due to findings of cardiovascular events.

Results A total of 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140). ARPEGGIO did not meet the primary endpoint of significant treatment effect with laquinimod 0.6 mg vs placebo on PBVC from baseline to week 48 (adjusted mean difference = 0.016%, p = 0.903). Laquinimod 0.6 mg reduced the number of new T2 brain lesions at week 48 (risk ratio 0.4; 95% confidence interval, 0.26–0.69; p = 0.001). Incidence of adverse events was higher among patients treated with laquinimod 0.6 mg (83%) vs laquinimod 1.5 mg (66%) and placebo (78%).

Conclusions Laquinimod 0.6 mg did not demonstrate a statistically significant effect on brain volume loss in PPMS at week 48.

Clinicaltrials.gov identifier NCT02284568.

Classification of evidence This study provides Class I evidence that, although well tolerated, laquinimod 0.6 mg did not demonstrate a significant treatment effect on PBVC in patients with PPMS.

Glossary

9HPT=
9-Hole Peg Test;
AE=
adverse event;
ALLEGRO RRMS=
Assessment of Oral Laquinimod in Preventing Progression in Multiple Sclerosis;
ARPEGGIO=
A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes;
BICAMS=
Brief International Cognitive Assessment for MS;
BRAVO=
Laquinimod Double Blind Placebo Controlled Study in RRMS Patients With a Rater Blinded Reference Arm of Interferon β-1a (Avonex®);
CDP=
confirmed disability progression;
CI=
confidence interval;
CONCERTO=
The Efficacy, Safety, and Tolerability of Laquinimod in Participants With Relapsing Remitting Multiple Sclerosis;
DMC=
data monitoring committee;
EDSS=
Expanded Disability Status Scale;
ET=
early termination;
FSS=
Functional System Score;
Gd+=
gadolinium-enhancing;
INFORMS=
Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS;
ITT=
intention-to-treat;
LCVA=
low-contrast visual acuity;
mITT1=
modified intention-to-treat 1 population;
mITT2=
modified intention-to-treat 2 population;
MS=
multiple sclerosis;
MSWS-12=
12-Item Multiple Sclerosis Walking Scale;
MTR=
magnetization transfer ratio;
PBVC=
percent brain volume change;
PPMS=
primary progressive multiple sclerosis;
RRMS=
relapsing-remitting multiple sclerosis;
SDMT=
Symbol Digit Modalities Test;
SPRINT-MS=
A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects With Progressive Multiple Sclerosis;
T25FW=
Timed 25-Foot Walk

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Class of Evidence: NPub.org/coe

  • Received July 9, 2019.
  • Accepted in final form February 20, 2020.
  • © 2020 American Academy of Neurology
View Full Text

AAN Members

We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.

Google Safari Microsoft Edge Firefox

Click here to login

AAN Non-Member Subscribers

Click here to login

Purchase access

For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)

Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here 

Purchase
Individual access to articles is available through the Add to Cart option on the article page.  Access for 1 day (from the computer you are currently using) is US$ 39.00.  Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means.  The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use.  Distributing copies (electronic or otherwise) of the article is not allowed.

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
  • Article
    • Abstract
    • Glossary
    • Methods
    • Results
    • Discussion
    • Study funding
    • Disclosure
    • Acknowledgment
    • Appendix Authors
    • Footnotes
    • References
  • Figures & Data
  • Info & Disclosures
Advertisement

Effect of Atogepant for Preventive Migraine Treatment on Patient-Reported Outcomes in the Randomized, Double-blind, Phase 3 ADVANCE Trial

Dr. Jessica Ailani and Dr. Ailna Masters-Israilov

► Watch

Related Articles

  • No related articles found.

Topics Discussed

  • Class I
  • Clinical trials Randomized controlled (CONSORT agreement)
  • Multiple sclerosis

Alert Me

  • Alert me when eletters are published

Recommended articles

  • Article
    Correlation between brain volume loss and clinical and MRI outcomes in multiple sclerosis
    Ernst-Wilhelm Radue, Frederik Barkhof, Ludwig Kappos et al.
    Neurology, January 28, 2015
  • Article
    Siponimod and Cognition in Secondary Progressive Multiple Sclerosis
    EXPAND Secondary Analyses
    Ralph H.B. Benedict, Davorka Tomic, Bruce A. Cree et al.
    Neurology, December 16, 2020
  • Article
    Aryl Hydrocarbon Receptor Plasma Agonist Activity Correlates With Disease Activity in Progressive MS
    Thanos Tsaktanis, Tobias Beyer, Lucy Nirschl et al.
    Neurology: Neuroimmunology & Neuroinflammation, December 24, 2020
  • Article
    Epigallocatechin Gallate in Progressive MS
    A Randomized, Placebo-Controlled Trial
    Rebekka Rust, Claudia Chien, Michael Scheel et al.
    Neurology: Neuroimmunology & Neuroinflammation, February 23, 2021
Neurology: 100 (23)

Articles

  • Ahead of Print
  • Current Issue
  • Past Issues
  • Popular Articles
  • Translations

About

  • About the Journals
  • Ethics Policies
  • Editors & Editorial Board
  • Contact Us
  • Advertise

Submit

  • Author Center
  • Submit a Manuscript
  • Information for Reviewers
  • AAN Guidelines
  • Permissions

Subscribers

  • Subscribe
  • Activate a Subscription
  • Sign up for eAlerts
  • RSS Feed
Site Logo
  • Visit neurology Template on Facebook
  • Follow neurology Template on Twitter
  • Visit Neurology on YouTube
  • Neurology
  • Neurology: Clinical Practice
  • Neurology: Education
  • Neurology: Genetics
  • Neurology: Neuroimmunology & Neuroinflammation
  • AAN.com
  • AANnews
  • Continuum
  • Brain & Life
  • Neurology Today

Wolters Kluwer Logo

Neurology | Print ISSN:0028-3878
Online ISSN:1526-632X

© 2023 American Academy of Neurology

  • Privacy Policy
  • Feedback
  • Advertise