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

نویسندگان

  • David H. Miller
  • Robert J. Fox
  • J. Theodore Phillips
  • Michael Hutchinson
  • Eva Havrdova
  • Mariko Kita
  • Claudia A.M. Wheeler-Kingshott
  • Daniel J. Tozer
  • David G. MacManus
  • Tarek A. Yousry
  • Mary Goodsell
  • Minhua Yang
  • Ray Zhang
  • Vissia Viglietta
  • Katherine T. Dawson
  • Kate Wilson
  • Jack Antel
  • James Ware
  • Chris Polman
  • Peter R. Kowey
  • Raymond Chung
  • George Bakris
  • John Richert
  • Burt Seibert
  • David Brandes
  • David Brassat
  • Bruce Cohen
  • Ricarda Diem
  • Myla Goldman
  • Robert Herndon
  • Aaron Miller
  • Hayrettin Tumani
  • Teresa Alfaro-Vidal
  • Carolina Crespo
  • Jo Foster
  • Kelvin Hunter
  • Almudena Garcia-Gomez
  • David MacManus
  • David Miller
  • Virginia Santana
  • Dan Tozer
  • Claudia Wheeler-Kingshott
  • Tarek Yousry
  • Christopher Kneebone
  • Aliaksandr Fedulau
  • Sergey Likhachev
  • Elena Mikhailova
  • Halina Naumova
  • Danny Decoo
  • Luc Vande Gaer
  • Christian Sindic
  • Sanja Grgic
  • Osman Sinanovic
  • Enra Mehmedika Suljic
  • Nadezhda Deleva
  • Dimitar Georgiev
  • Lyubomir Haralanov
  • Sonyia Ivanova
  • Ivan Manchev
  • Dimitar Minchev
  • Paraskeva Stamenova
  • Ivailo Tournev
  • Elena Vacheva
  • Zahari Zahariev
  • Amit Bar-Or
  • Gregg Blevins
  • Marcelo Kremenchutzky
  • Felix Veloso
  • Norbert Witt
  • Roberto Vargas Howell
  • Alexander Parajeles Vindas
  • Mario Habek
  • Josip Rudež
  • Silva Soldo-Butković
  • Ranka Baraba Vurdelja
  • David Doležil
  • Jiří Nova'k
  • Daniel Vaclavik
  • Katrin Antsov
  • Katrin Gross-Paju
  • Sulev Haldre
  • Alla Palu
  • Toomas Toomsoo
  • Abdullatif Al Khedr
  • William Camu
  • Marc Debouverie
  • Gilles Defer
  • Jérôme De Seze
  • Pierre Labauge
  • Thibault Moreau
  • Jean Pelletier
  • Lucien Rumbach
  • Vera Daskalovska
  • Klemens Angnstwurm
  • Heike Benes
  • Achim Berthele
  • Hans-Jürgen Boldt
  • Angelika Christopher
  • Tobias Derfuß
  • Ilonka Eisensehr
  • Peter Emrich
  • Wolfgang Feneberg
  • Frank Hoffmann
  • Reinhard Hohlfeld
  • Reinhard Hüntemann
  • Boris-Alexander Kallmann
  • Bernd Kieseier
  • Harald Landefeld
  • Wilfried Lüer
  • Sabine Masri
  • Gereon Nelles
  • Patrick Oschmann
  • Christine Paschen
  • Gerd Reifschneider
  • Michael Sailer
  • Sebastian Schimrigk
  • Mechthild Spiegel-Meixensberger
  • Brigitte Storch-Hagenlocher
  • Björn Tackenberg
  • Klaus Tiel-Wilck
  • Clementine Karageorgiou
  • Panagiotis Papathanasopoulos
  • Thomas Thomaides
  • Nicholas Vlaikidis
  • Deepak Arjundas
  • Madhuri Behari
  • Amitabha Ghosh
  • Pahari Ghosh
  • Nasli Rustom Ichaporia
  • Dheeraj Khurana
  • Rahul Vitthal Kulkarni
  • Suresh Kumar
  • Man Mohan Mehndiratta
  • Neeta Abhay Mehta
  • Usha Kant Misra
  • Joy Dev Mukherji
  • Shankara Nellikunja
  • Abdul Salem
  • Prahlad Kumar Sethi
  • Shalin Dipinkumar Shah
  • Gagandeep Singh
  • Maneesh Kumar Singh
  • Yash Pal Singh
  • Rangasetty Srinivasa
  • Krishnan Vijayan
  • Bernard Sweeney
  • Ronit Gilad
  • Radi Shahien
  • Anita Paegle
  • Cesar Delgado
  • Juan Escamilla
  • Bruno Estañol
  • Minerva Lopez
  • Miguel Angel Macias
  • Guillermo Punzo
  • Sandra Quiñones
  • Mariela Renteria
  • Jose Santos
  • Mihail Gavriliuc
  • Stanislav Groppa
  • Olesea Odainic
  • Paul Timmings
  • Anna Czlonkowska
  • Malgorzata Dorobek
  • Wieslaw Drozdowski
  • Waldemar Fryze
  • Hanka Hertmanowska
  • Anna Kaminska
  • Magdalena Kapelusiak-Pielok
  • Magdalena Kleczkowska
  • Jan Kochanowicz
  • Jacek Losy
  • Przemyslaw Nowacki
  • Walenty Nyka
  • Krystyna Pierzchala
  • Ryszard Podemski
  • Andrzej Potemkowski
  • Krzysztof Selmaj
  • Zbigniew Stelmasiak
  • Andrzej Szczudlik
  • Andrzej Tutaj
  • Andrzej Wajgt
  • Tomasz Zielinski
  • Rodica Balasa
  • Valentin Ionescu-Dimancea
  • Petru Mihancea
  • Cristian Popescu
  • Liviu Codrut Protosevici
  • Svetlana Miletić Drakulić
  • Congor Nadj
  • Ranko Raicevic
  • Slobodan Vojinovic
  • Edita Kahancová
  • Egon Kurca
  • L'ubomir Lisý
  • Peter Turčáni
  • Rafael Arroyo
  • Oscar Fernández
  • Cristina Guijarro
  • Guillermo Izquierdo
  • Fernando Sanchez Lopez
  • Xavier Montalbán
  • Celia Oreja-Guevara
  • Jose Maria Prieto
  • Nataliya Buchakchyys'ka
  • Galyna Chmyr
  • Alla Goloborodko
  • Tetyana Kobys
  • Grygory Kushnir
  • Volodymyr Lebedynets
  • Nataliya Lytvynenko
  • Sergii Moskovko
  • Tetyana Nehrych
  • Borys Palamar
  • Igor Pasyura
  • Tatyana Ryabichenko
  • Nataliya Voloshina
  • Michelle Apperson
  • Angela Applebee
  • Stephen Asher
  • Ricardo Ayala
  • Donald Ayres
  • S. Ausim Azizi
  • Matthew Baker
  • Brendan Bauer
  • Roberto Bomprezzi
  • Richard Buckler
  • Walter Carlini
  • Angel Chinea
  • Stanley Cohan
  • Giles Crowell
  • Keith Edwards
  • Geoffery Eubank
  • Warren Felton
  • Patricia Fodor
  • John Foley
  • Corey Ford
  • Edward Fox
  • Robert Fox
  • Mary Forester
  • Steven Freedman
  • George Garmany
  • Suzanne Gazda
  • Daniel Giang
  • Braeme Glaun
  • Scott Gold
  • Malcolm Gottesman
  • Mark Gudesblatt
  • Joseph Herbert
  • Allan Herskowitz
  • William Honeycutt
  • John Huddlestone
  • Richard Hull
  • Samuel Hunter
  • George Hutton
  • Dina Jacobs
  • Mark Janicki
  • Bhupendra Khatri
  • Revere Philip Kinkel
  • Stanley Krolczyk
  • Lauren Krupp
  • Christopher LaGanke
  • Michael Levin
  • Jonathan Licht
  • Christopher Luzzio
  • Sharon Lynch
  • David Mattson
  • Daniel Mikol
  • Tamara Miller
  • Alireza Minagar
  • Galen Mitchell
  • Harold Moses
  • Donald Negroski
  • Stephen Newman
  • Gabriel Pardo
  • Malti Patel
  • Allan Perel
  • Joseph Phillips
  • Mary Ann Picone
  • Kottil Rammohan
  • T. Hemanth Rao
  • John Rinker
  • Saud Sadiq
  • John Schaeffer
  • William Sheremata
  • Robert Shin
  • Richard Shubin
  • Stuart Silverman
  • Robert Smith
  • Lee Stein
  • Michael Stein
  • David Steiner
  • Brian Steingo
  • Herman Sullivan
  • William Sunter
  • Anand Vaishnav
  • Alberto Vasquez
  • James Voci
  • Jonathan Warach
  • Bianca Weinstock-Guttman
  • Mitzi Williams
  • Sibyl Wray
چکیده

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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عنوان ژورنال:

دوره 84  شماره 

صفحات  -

تاریخ انتشار 2015