PMID- 33796143
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220421
IS  - 1756-2856 (Print)
IS  - 1756-2864 (Electronic)
IS  - 1756-2856 (Linking)
VI  - 14
DP  - 2021
TI  - Improved gastrointestinal profile with diroximel fumarate is associated with a 
      positive impact on quality of life compared with dimethyl fumarate: results from 
      the randomized, double-blind, phase III EVOLVE-MS-2 study.
PG  - 1756286421993999
LID - 10.1177/1756286421993999 [doi]
LID - 1756286421993999
AB  - BACKGROUND: Diroximel fumarate (DRF) is a novel oral fumarate approved for 
      relapsing forms of multiple sclerosis (MS). DRF demonstrated significantly 
      improved gastrointestinal (GI) tolerability versus dimethyl fumarate (DMF) with 
      fewer days of Individual Gastrointestinal Symptom and Impact Scale (IGISIS) 
      scores ⩾2, GI adverse events (AEs), and treatment discontinuations due to GI AEs. 
      Our aim was to evaluate the impact of GI tolerability events on quality of life 
      (QoL) for patients with relapsing-remitting MS who received DRF or DMF in 
      EVOLVE-MS-2. METHODS: A post hoc analysis was conducted in patients who were 
      enrolled in the randomized, blinded, 5-week, EVOLVE-MS-2 [ClinicalTrials.gov 
      identifier: NCT03093324] study of DRF versus DMF. Patients completed daily IGISIS 
      and Global GISIS (GGISIS) eDiary questionnaires to assess GI symptom intensity 
      and interference with daily activities and work. RESULTS: In total, 504 patients 
      (DRF, n = 253; DMF, n = 251) received study drug and 502 (DRF, n = 253; DMF, 
      n = 249) completed at least one post-baseline questionnaire. With DRF, GI 
      symptoms were less likely to interfere 'quite a bit' or 'extremely' with regular 
      daily activities [IGISIS: DRF, 9.5% (24/253) versus DMF, 28.9% (72/249)] or work 
      productivity [GGISIS: DRF, 6.1% (10/165) versus DMF, 11.3% (18/159)]. DRF-treated 
      patients had fewer days with ⩾1 h of missed work (DRF, 43 days, n = 20 versus 
      DMF, 88 days, n = 26). DMF-treated patients reported highest GI symptom severity 
      and missed work at week 2-3 shortly after completing the titration period, which 
      coincided with the majority of GI-related treatment discontinuations [58.3% 
      (7/12)]. GI tolerability AEs [DRF, 34.8% (88/253); DMF, 48.2% (121/251)], 
      concomitant symptomatic medication use [DRF, 19.3% (17/88) versus DMF, 30.6% 
      (37/121)], and GI-related discontinuations (DRF, 0.8% versus DMF, 4.8%) were 
      lower with DRF versus DMF. CONCLUSIONS: The improved GI tolerability with DRF 
      translated into clinically meaningful benefits to QoL, as patients experienced 
      less impact on daily life and work and required less concomitant symptomatic 
      medication use. TRIAL REGISTRATION: [ClinicalTrials.gov identifier: NCT03093324].
CI  - (c) The Author(s), 2021.
FAU - Wundes, Annette
AU  - Wundes A
AD  - Department of Neurology, University of Washington Medical Center, Seattle, WA, 
      USA.
FAU - Wray, Sibyl
AU  - Wray S
AD  - Hope Neurology MS Center, Knoxville, TN, USA.
FAU - Gold, Ralf
AU  - Gold R
AD  - Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, 
      Germany.
FAU - Singer, Barry A
AU  - Singer BA
AD  - The MS Center for Innovations in Care, Missouri Baptist Medical Center, St. 
      Louis, MO, USA.
FAU - Jasinska, Elzbieta
AU  - Jasinska E
AD  - Collegium Medicum UJK and Clinical Center, RESMEDICA, Kielce, Poland.
FAU - Ziemssen, Tjalf
AU  - Ziemssen T
AUID- ORCID: 0000-0001-8799-8202
AD  - Center of Clinical Neuroscience, Carl Gustav Carus University Hospital, Dresden, 
      Germany.
FAU - de Seze, Jerome
AU  - de Seze J
AD  - Strasbourg University Hospital and Clinical Investigation Center, INSER 1434, 
      Strasbourg, France.
FAU - Repovic, Pavle
AU  - Repovic P
AD  - Multiple Sclerosis Center, Swedish Neuroscience Institute, Seattle, WA, USA.
FAU - Chen, Hailu
AU  - Chen H
AD  - Biogen, Cambridge, MA, USA.
FAU - Hanna, Jerome
AU  - Hanna J
AD  - Biogen, Maidenhead, UK.
FAU - Messer, Jordan
AU  - Messer J
AUID- ORCID: 0000-0002-8861-3455
AD  - Biogen, 225 Binney Street, Cambridge, MA 02142-1031, USA.
FAU - Miller, Catherine
AU  - Miller C
AUID- ORCID: 0000-0001-5135-1722
AD  - Biogen, Cambridge, MA, USA.
FAU - Naismith, Robert T
AU  - Naismith RT
AD  - Washington University School of Medicine, St. Louis, MO, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03093324
PT  - Journal Article
DEP - 20210319
PL  - England
TA  - Ther Adv Neurol Disord
JT  - Therapeutic advances in neurological disorders
JID - 101480242
PMC - PMC7985943
OTO - NOTNLM
OT  - clinical trial
OT  - diroximel fumarate
OT  - disease-modifying therapy
OT  - gastrointestinal
OT  - relapsing-remitting multiple sclerosis
COIS- Conflict of interest statement: AW reports advisor fees from Biogen and AbbVie; 
      and research support from AbbVie, Alkermes, and Biogen. SW reports consulting 
      fees from Biogen, EMD Serono, Genentech-Roche, Sanofi-Genzyme; speaker bureaus 
      for Biogen, EMD Serono, Genentech/Roche, and Sanofi-Genzyme; and research support 
      from Alkermes, Biogen, Celgene, Genentech/Roche, Novartis, Sanofi-Genzyme, and 
      TG. RG reports honoraria from Bayer, Biogen, Merck Serono, Novartis, and Teva 
      Neuroscience; and research support from Bayer, Biogen, Merck Serono, Novartis, 
      and Teva Neuroscience. BAS reports speaker/consulting fees from AbbVie, Alexion, 
      Bayer, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Novartis, Roche, 
      Sanofi-Genzyme, Teva, and TG; and research support from AbbVie, Alkermes, Biogen, 
      MedImmune, Novartis, Roche, and Sanofi-Genzyme. EJ reports advisory boards for 
      Biogen; and speaker fees from Adamed, Allergan, Novartis, Polpharma, Roche, and 
      Teva. TZ reports advisory boards for Bayer, Biogen, Genzyme, Merck Serono, 
      Novartis, Synthon, and Teva; speaker fees from Almirall, Bayer, Biogen, Genzyme, 
      GlaxoSmithKline, Merck Sharp & Dohme, Novartis, Sanofi, and Teva; and research 
      support from Bayer, Biogen, Genzyme, Novartis, Sanofi, and Teva. JDS reports 
      honoraria from Biogen for advisory boards and consulting. PR reports 
      speaker/consulting fees from Alexion, Biogen, Celgene, EMD Serono, Medison, 
      Novartis, Roche, Sanofi-Genzyme, and Viela Bio. HC, JH, JM, and CM are employees 
      of and hold stock/stock options in Biogen. RTN reports advisor/speaker/consulting 
      fees from Alexion, Alkermes, Bayer, Biogen, Celgene, EMD Serono, Genentech, 
      Lundbeck, NervGen, Novartis, Sanofi-Genzyme, Third Rock, and Viela Bio. The 
      Editor-in-Chief of Therapeutic Advances in Neurological Disorders is an author of 
      this paper, therefore, the peer review process was managed by alternative members 
      of the Board and the Editor was not involved in the decision-making process.
EDAT- 2021/04/03 06:00
MHDA- 2021/04/03 06:01
PMCR- 2021/03/19
CRDT- 2021/04/02 06:32
PHST- 2020/09/23 00:00 [received]
PHST- 2021/01/15 00:00 [accepted]
PHST- 2021/04/02 06:32 [entrez]
PHST- 2021/04/03 06:00 [pubmed]
PHST- 2021/04/03 06:01 [medline]
PHST- 2021/03/19 00:00 [pmc-release]
AID - 10.1177_1756286421993999 [pii]
AID - 10.1177/1756286421993999 [doi]
PST - epublish
SO  - Ther Adv Neurol Disord. 2021 Mar 19;14:1756286421993999. doi: 
      10.1177/1756286421993999. eCollection 2021.