Evidence map›Paper›PMID 37061656›Full record

ArticleNeurology and therapy2023

Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies.

Lilyana Amezcua, Yang Mao-Draayer, Wendy S Vargas, Rebecca Farber, Sara Schaefer, Filipe Branco, Sarah M England, Nicholas Belviso, James B Lewin, Jason P Mendoza and 2 more

3 registry-linked trialsOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology and therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00420212 phase3completednot on this map

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Dose-Comparison Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis

TypeinterventionalSponsorBiogenRan2007 to 2011Enrolled1,234ConditionsRelapsing-Remitting Multiple SclerosisArmsBG00012, Placebo
NCT00451451 phase3completednot on this map

A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis

TypeinterventionalSponsorBiogenRan2007 to 2011Enrolled1,417ConditionsRelapsing-Remitting Multiple SclerosisArmsBG00012, Placebo, Glatiramer Acetate
NCT00835770 phase3completednot on this map

A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis

TypeinterventionalSponsorBiogenRan2009 to 2019Enrolled1,736ConditionsRelapsing-Remitting Multiple SclerosisArmsdimethyl fumarate, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Lilyana AmezcuaMultiple Sclerosis Comprehensive Care Center, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1542-7819
Yang Mao-DraayerAutoimmunity Center of Excellence, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-6248-3480
Wendy S VargasColumbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Rebecca FarberColumbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Sara SchaeferMultiple Sclerosis Comprehensive Care Center, UC-Health Neurology Clinic, Fort Collins, CO, USA.
Filipe BrancoBiogen, Cambridge, MA, USA.
Sarah M EnglandBiogen, Cambridge, MA, USA.
Nicholas BelvisoBiogen, Cambridge, MA, USA.
James B LewinBiogen, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2352-9113
Jason P MendozaBiogen, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2526-5542
Sai L ShankarBiogen, Cambridge, MA, USA. sai.shankar@biogen.com.ORCID http://orcid.org/0000-0003-3249-8360
ENDORSE Study Investigators
Biogen (United States) · USColumbia University Irving Medical Center · USUniversity of Michigan · USUniversity of Southern California · US

Funding

Viral Assays CoreU19AI128949 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Donna L. Farber, Peter Alan Sims · 2017 to 2026
$26.4M
CD24 Targeting for Multiple Sclerosis: a First-In-Human Phase I StudyR01NS080821 · NINDS · ONCOIMMUNE, INC. · PI LIU, YANG · 2013 to 2014
$1.1M
University of Michigan Autoimmunity Center of Excellence, Clinical Research ProgrUM1AI110557 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FOX, DAVID ALAN · 2014 to 2018
$543k
NIAID NIH HHS U19 AI128949NIAID NIH HHS UM1 AI110557NINDS NIH HHS R01 NS080821
6 · The paper itself

Abstract

introductionDimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population.

methodsRandomized patients received DMF 240 mg twice daily or placebo (PBO; years 0-2 DEFINE/CONFIRM), then DMF (years 3-10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18-29 years.

resultsOf 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0-10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16-0.35) vs. 0.56 (0.35-0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01-0.47) at years 9-10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]).

conclusionThe data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. CLINICAL TRIAL INFORMATION: Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770).

Indexed as

Dimethyl fumarateDMTEfficacyMultiple sclerosisSafetyYoung adults

Identifiers

PMID37061656
PMCPMC10195942
OpenAlexW4365812415

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.