Evidence map›Paper›PMID 38335474›Full record

Trial reportNeurology2024

Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.

Douglas L Arnold, Colm Elliott, Emily C Martin, Yann Hyvert, Davorka Tomic, Xavier Montalban

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02975349 (A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% 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.

NCT02975349 phase2terminatednot on this map

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.

TypeinterventionalSponsorEMD Serono Research & Development Institute, Inc.Ran2017 to 2024Enrolled267ConditionsRelapsing-remitting Multiple SclerosisArmsEvobrutinib, Placebo, Tecfidera
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
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  10. Unraveling the Effects ofInternational journal of molecular sciences · 2025
    Review
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  17. Imaging Outcomes for Phase 2 Trials Targeting Compartmentalized Inflammation.Multiple sclerosis (Houndmills, Basingstoke, England) · 2024
    Review
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  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 3 countries.

Douglas L ArnoldFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.
Colm ElliottFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.ORCID 0000-0002-3004-523X
Emily C MartinFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.
Yann HyvertFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.
Davorka TomicFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.
Xavier MontalbanFrom the Montreal Neurological Institute (D.L.A.), McGill University; NeuroRx Research (D.L.A., C.E.), Montreal, Quebec, Canada; EMD Serono (E.C.M.), Billerica, MA; The Healthcare Business of Merck KGaA (Y.H.); Ares Trading SA (D.T.), Eysins, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany; and Centre d'Esclerosi Múltiple de Catalunya (Cemcat) (X.M.), Hospital Universitario Vall d'Hebron, Barcelona, Spain.ORCID 0000-0002-0098-9918
Montreal Neurological Institute and Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesChronic active lesions (CALs) are demyelinated multiple sclerosis (MS) lesions with ongoing microglia/macrophage activity, resulting in irreversible neuronal damage and axonal loss. Evobrutinib is a highly selective, covalent, CNS-penetrant, Bruton tyrosine kinase inhibitor. This post hoc analysis evaluated the effect of evobrutinib on slowly expanding lesion (SEL) volume, an MRI marker of CALs, assessed baseline-week 48 in a phase 2, double-blind, randomized trial (NCT02975349) in relapsing MS (RMS).

methodsIn the 48-week, double-blind trial, adult patients received evobrutinib (25 mg once daily [QD], 75 mg QD, or 75 mg twice daily [BID]), placebo (switched to evobrutinib 25 mg QD after week 24), or open-label dimethyl fumarate (DMF) 240 mg BID. SELs were defined as slowly and consistently radially expanding areas of preexisting T2 lesions of ≥10 contiguous voxels (∼30 mm

resultsThe SEL analysis set included 223 patients (mean [SD] age: 42.4 [10.7] years; 69.3% female; 87.4% relapsing/remitting MS). Mean (SD) SEL volume was 2,099 (2,981.0) mm DISCUSSION: Evobrutinib reduced SEL volume in a dose-dependent manner in RMS, with a significant reduction with evobrutinib 75 mg BID. This is evident that evobrutinib affects brain lesions associated with chronic inflammation and tissue loss. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT02975349. Submitted to ClinicalTrials.gov on November 29, 2016. First patient enrolled: March 7, 2017. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that evobrutinib reduces the volume of SELs assessed on MRI comparing baseline with week 48, in patients with RMS.

Indexed as

Multiple SclerosisMultiple Sclerosis, Relapsing-RemittingPyrimidinesAdultDimethyl FumarateDouble-Blind MethodFemaleHumansMalePiperidinesRecurrenceDimethyl FumarateevobrutinibPiperidinesPyrimidines

Identifiers

PMID38335474
PMCPMC11067693
OpenAlexW4391708005

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.