title: Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study.
abstract: 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.
  
  
  METHODS
  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.
authors: 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.
authors: David H
authors: DH
authors: Miller
authors: 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.
authors: Robert J
authors: RJ
authors: Fox
authors: 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.
authors: J Theodore
authors: JT
authors: Phillips
authors: 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.
authors: Michael
authors: M
authors: Hutchinson
authors: 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.
authors: Eva
authors: E
authors: Havrdova
authors: 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.
authors: Mariko
authors: M
authors: Kita
authors: 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.
authors: Claudia A M
authors: CA
authors: Wheeler-Kingshott
authors: 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.
authors: Daniel J
authors: DJ
authors: Tozer
authors: 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.
authors: David G
authors: DG
authors: MacManus
authors: 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.
authors: Tarek A
authors: TA
authors: Yousry
authors: 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.
authors: Mary
authors: M
authors: Goodsell
authors: 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.
authors: Minhua
authors: M
authors: Yang
authors: 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.
authors: Ray
authors: R
authors: Zhang
authors: 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.
authors: Vissia
authors: V
authors: Viglietta
authors: 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.
authors: Katherine T
authors: KT
authors: Dawson
mesh_terms: D000293:Adolescent; D000328:Adult; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D000069462:Dimethyl Fumarate; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D038622:Internationality; D008279:Magnetic Resonance Imaging / Q000639:trends; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D005650:Fumarates; D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate