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Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study

DH. Miller, RJ. Fox, JT. Phillips, M. Hutchinson, E. Havrdova, M. Kita, CA. Wheeler-Kingshott, DJ. Tozer, DG. MacManus, TA. Yousry, M. Goodsell, M. Yang, R. Zhang, V. Viglietta, KT. Dawson, . ,

Miller, David H
Autor Miller, David H From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA. david.h.miller@ucl.ac.uk
Fox, Robert J
Autor Fox, Robert J From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Phillips, J Theodore
Autor Phillips, J Theodore From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Hutchinson, Michael
Autor Hutchinson, Michael From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Havrdova, Eva
Autor Havrdova, Eva From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Kita, Mariko
Autor Kita, Mariko From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Wheeler-Kingshott, Claudia A M
Autor Wheeler-Kingshott, Claudia A M From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Tozer, Daniel J
Autor Tozer, Daniel J From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
MacManus, David G
Autor MacManus, David G From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Yousry, Tarek A
Autor Yousry, Tarek A From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Goodsell, Mary
Autor Goodsell, Mary From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Yang, Minhua
Autor Yang, Minhua From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Zhang, Ray
Autor Zhang, Ray From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Viglietta, Vissia
Autor Viglietta, Vissia From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA
Dawson, Katherine T
Autor Dawson, Katherine T From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic Virginia Mason Medical Center (M.K.), Seattle, WA CircleScience (M.G.), Tytherington, UK and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA

Neurology. 2015 ; 84 (11) : 1145-52.

ISSN 1526-632X
Medvik
Zdroj

Jazyk angličtina Země Spojené státy americké

Typ dokumentu klinické zkoušky, fáze III, časopisecké články, multicentrická studie, randomizované kontrolované studie, práce podpořená grantem

Perzistentní odkaz https://www.medvik.cz/link/bmc15022818

PubMed 25681448
DOI 10.1212/wnl.0000000000001360
Knihovny.cz E-zdroje

OBJECTIVE: To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS: CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS: DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS: The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.

Biogen Idec Incorporated Weston MA

CircleScience Tytherington UK

Department of Neurology 1st Faculty of Medicine Charles University Prague Czech Republic

From the Departments of Neuroinflammation NMR Research Unit Queen Square Multiple Sclerosis Centre

Mellen Center for Multiple Sclerosis Treatment and Research Cleveland Clinic OH

Multiple Sclerosis Program Baylor Institute for Immunology Research Dallas TX

St Vincent's University Hospital Elm Park Donnybrook Dublin Ireland

University College London Institute of Neurology UK

Virginia Mason Medical Center Seattle WA

Citace poskytuje Crossref.org

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100 1_: $a Miller, David H $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA. david.h.miller@ucl.ac.uk.

245 10: $a Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study / $c DH. Miller, RJ. Fox, JT. Phillips, M. Hutchinson, E. Havrdova, M. Kita, CA. Wheeler-Kingshott, DJ. Tozer, DG. MacManus, TA. Yousry, M. Goodsell, M. Yang, R. Zhang, V. Viglietta, KT. Dawson, . ,

520 9_: $a OBJECTIVE: To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study. METHODS: CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort). RESULTS: DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance. CONCLUSIONS: The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.

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700 1_: $a Fox, Robert J $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Phillips, J Theodore $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Hutchinson, Michael $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Havrdova, Eva $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Kita, Mariko $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Wheeler-Kingshott, Claudia A M $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Tozer, Daniel J $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a MacManus, David G $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Yousry, Tarek A $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Goodsell, Mary $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Yang, Minhua $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Zhang, Ray $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Viglietta, Vissia $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

700 1_: $a Dawson, Katherine T $u From the Departments of Neuroinflammation (D.H.M., C.A.M.W.-K., D.J.T., D.G.M.) and Brain Repair and Rehabilitation (T.A.Y.), NMR Research Unit, Queen Square Multiple Sclerosis Centre; University College London Institute of Neurology (D.H.M., C.A.M.W.-K., D.J.T., D.G.M., T.A.Y.), UK; Mellen Center for Multiple Sclerosis Treatment and Research (R.J.F.), Cleveland Clinic, OH; Multiple Sclerosis Program (J.T.P.), Baylor Institute for Immunology Research, Dallas, TX; St. Vincent's University Hospital (M.H.), Elm Park, Donnybrook, Dublin, Ireland; Department of Neurology (E.H.), First Faculty of Medicine, Charles University, Prague, Czech Republic; Virginia Mason Medical Center (M.K.), Seattle, WA; CircleScience (M.G.), Tytherington, UK; and Biogen Idec Incorporated (M.Y., R.Z., V.V., K.T.D.), Weston, MA.

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