Evidence map›Paper›PMID 38878121›Full record

Trial reportAdvances in therapy2024

Diroximel Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: NEDA-3 After Re-Baselining in the Phase 3 EVOLVE-MS-1 Study.

James D Bowen, Jessica Stulc, Samuel F Hunter, Hailu Chen, James B Lewin, Matthew Scaramozza, Ivan Bozin, Florian Then Bergh

2 registry-linked trialsAbstract readClinical Trial, Phase IIIRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Advances in therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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.

NCT02634307 phase3completednot on this map

A Phase 3 Open Label Study to Evaluate the Long-term Safety and Tolerability of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis

TypeinterventionalSponsorBiogenRan2015 to 2021Enrolled1,057ConditionsMultiple SclerosisArmsALKS 8700
NCT03093324 phase3completednot on this map

A Phase 3 Study in Subjects With Relapsing Remitting Multiple Sclerosis to Evaluate the Tolerability of ALKS 8700 and Dimethyl Fumarate

TypeinterventionalSponsorBiogenRan2017 to 2019Enrolled506ConditionsRelapsing Remitting Multiple SclerosisArmsALKS 8700, Dimethyl Fumarate
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

8 authors.

James D BowenSwedish Neuroscience Institute, Seattle, WA, USA.ORCID 0000-0002-4258-250X
Jessica StulcMinneapolis Clinic of Neurology, Golden Valley, MN, USA.
Samuel F HunterAdvanced Neurosciences Institute, Franklin, TN, USA.ORCID 0000-0002-0542-1176
Hailu ChenBiogen, Cambridge, MA, USA.
James B LewinBiogen, Cambridge, MA, USA.ORCID 0000-0002-2352-9113
Matthew ScaramozzaBiogen, Cambridge, MA, USA.
Ivan BozinBiogen, Neuhofstrasse 30, 6340, Baar, Switzerland. ivan.bozin@biogen.com.ORCID 0009-0008-2205-4233
Florian Then BerghDepartment of Neurology, University of Leipzig, Leipzig, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDiroximel fumarate (DRF) and dimethyl fumarate (DMF) are orally administered fumarate disease-modifying therapies (DMTs) for multiple sclerosis (MS). The safety, tolerability, and exploratory efficacy of DRF were evaluated in the phase 3 EVOLVE-MS-1 study. No Evidence of Disease Activity (NEDA-3) is a composite efficacy endpoint used in clinical trials for MS defined as no relapse, no 24-week confirmed disability progression (CDP), no new/newly enlarging T2 lesions, and no new gadolinium-enhancing lesions. As NEDA outcomes in studies may be confounded by initial disease activity, the objective of this analysis was to evaluate NEDA-3 in EVOLVE-MS-1 for newly enrolled patients and patients who were re-baselined after approximately 7 weeks.

methodsPatients entered EVOLVE-MS-1 as either newly enrolled or having completed the 5-week phase 3 EVOLVE-MS-2 study of DRF and DMF. Magnetic Resonance Imaging (MRI) was performed at baseline before each study (approx. 7 weeks apart) and at weeks 48 and 96 in EVOLVE-MS-1. Therefore, patients entering from EVOLVE-MS-2 were re-baselined after approximately 7 weeks. NEDA-3 outcomes on DRF are reported for prior DRF, prior DMF, and de novo patient groups.

resultsOf 1057 patients in EVOLVE-MS-1, 239 (22.6%) had rolled over from receiving DRF in EVOLVE-MS-2 ("prior DRF"), 225 (21.3%) had rolled over from receiving DMF in EVOLVE-MS-2 ("prior DMF"), and 593 (56.1%) were newly enrolled ("de novo"). At week 48, Kaplan-Meier estimates of NEDA-3 were 72.3% (prior DRF), 72.1% (prior DMF), and 62.1% (de novo); at week 96, estimates were 50.2% (prior DRF), 48.2% (prior DMF), and 36.5% (de novo).

conclusionsIn EVOLVE-MS-1, after re-baselining at approximately 7 weeks, approximately half of DRF-treated patients achieved NEDA-3 at week 96, compared with 36.5% of patients who were not re-baselined. Re-baselining may be useful for assessing efficacy of DMTs by mitigating the influence of disease activity prior to the onset of efficacy. CLINICAL TRIAL REGISTRATIONS: NCT03093324 (EVOLVE-MS-2); NCT02634307 (EVOLVE-MS-1).

Indexed as

Dimethyl FumarateFumaratesMagnetic Resonance ImagingMultiple Sclerosis, Relapsing-RemittingAdultDisease ProgressionDouble-Blind MethodFemaleHumansImmunosuppressive AgentsMaleMiddle AgedTreatment OutcomeDimethyl FumarateFumaratesImmunosuppressive AgentsDimethyl fumarateDiroximel fumarateDisease-modifying therapiesEfficacyMultiple sclerosisNo Evidence of Disease Activity (NEDA)Re-baselining

Identifiers

PMID38878121
PMCPMC11263382

What OpenQuestion holds

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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.