Evidence map›Paper›PMID 38935202›Full record

ArticleNeurology and therapy2024

Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study.

Barry A Singer, Sibyl Wray, Mark Gudesblatt, Barbara Bumstead, Tjalf Ziemssen, Ashley Bonnell, Matthew Scaramozza, Seth Levin, Mathura Shanmugasundaram, Hailu Chen and 3 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology and therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02634307 (A Phase 3 Open Label Study to Evaluate the Long-term Safety and Tolerability of ALKS 8700 in Adults With Relapsing Remitting Multiple Sclerosis), which is 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
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

13 authors.

Barry A SingerThe MS Center for Innovations in Care, Missouri Baptist Medical Center, St. Louis, MO, USA.ORCID http://orcid.org/0000-0001-6875-7374
Sibyl WrayHope Neurology MS Center, Knoxville, TN, USA.
Mark GudesblattNYU South Shore Neurologic Associates, Patchogue, NY, USA.ORCID http://orcid.org/0000-0002-3700-8554
Barbara BumsteadNYU South Shore Neurologic Associates, Patchogue, NY, USA.
Tjalf ZiemssenCenter of Clinical Neuroscience, Carl Gustav Carus University Hospital, TU Dresden, Dresden, Germany.ORCID http://orcid.org/0000-0001-8799-8202
Ashley BonnellHope Neurology MS Center, Knoxville, TN, USA.
Matthew ScaramozzaBiogen, 225 Binney St., Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-3738-459X
Seth LevinBiogen, 225 Binney St., Cambridge, MA, 02142, USA.
Mathura ShanmugasundaramBiogen, 225 Binney St., Cambridge, MA, 02142, USA.
Hailu ChenBiogen, 225 Binney St., Cambridge, MA, 02142, USA.
Jason P MendozaBiogen, 225 Binney St., Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0003-2526-5542
James B LewinBiogen, 225 Binney St., Cambridge, MA, 02142, USA.ORCID http://orcid.org/0000-0002-2352-9113
Sai L ShankarBiogen, 225 Binney St., Cambridge, MA, 02142, USA. Sai.Shankar@Biogen.com.ORCID http://orcid.org/0000-0003-3249-8360

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionIn EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia.

methodsEVOLVE-MS-1-an open-label, 96-week, phase 3 study-assessed DRF safety and exploratory efficacy in patients with relapsing-remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients with lymphopenia (≥ 1 ALC below lower limit of normal [LLN]) and without (all ALCs ≥ LLN); (2) across quartiles stratified by week 96 ALC decline from baseline: Q1 (≥ 47% decline); Q2 (30% to < 47% decline); Q3 (12% to < 30% decline); Q4 (< 12% decline).

resultsBaseline characteristics were similar between patients without (n = 593) and with lymphopenia (n = 452). At week 96, adjusted annualized relapse rate (ARR; 95% confidence interval) was 0.14 (0.11-0.17) without lymphopenia and 0.12 (0.09-0.15) with lymphopenia. Estimated proportions with 12-week confirmed disability progression (CDP12) at week 96 were 10.2% without and 9.3% with lymphopenia. When stratified by quartiles (Q1-Q4), ARR at week 96 was 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), and 0.17 (Q4). Estimated proportions with CDP12 at week 96 were 9.6% (Q1), 10.2% (Q2), 5.7% (Q3), and 10.9% (Q4). At week 96, no evidence of disease activity was achieved by 47.2% (Q1), 47.8% (Q2), 45.4% (Q3), and 37.3% (Q4) of patients.

conclusionIn DRF-treated patients in EVOLVE-MS-1, clinical and radiological measurements indicated reduced disease activity regardless of lymphopenia or magnitude of ALC decline from baseline; however, patients who had greater ALC declines appeared to have numerically lower ARR and higher proportions free from relapses and gadolinium-enhancing lesions compared with those with smallest decline. This supports prior evidence that, while lymphopenia may contribute to fumarate efficacy outcomes, it is not the primary mechanism of action.

trial registrationClinicalTrials.gov identifier NCT02634307.

Indexed as

Absolute lymphocyte countDiroximel fumarateEfficacyLymphopenia

Identifiers

PMID38935202
PMCPMC11263526

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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.