Evidence map›Paper›PMID 40770143›Full record

ArticleJournal of neurology2025

Real-world comparison of lymphopenia profiles in S1P receptor modulators for multiple sclerosis: a multicenter retrospective study.

Giorgia Teresa Maniscalco, Maddalena Sparaco, Maria Di Gregorio, Giuseppina Cafasso, Elisabetta Signoriello, Felice Romano, Rosa Iodice, Roberta Fantozzi, Paolo Bellantonio, Aurora Zanghi and 17 more

Abstract readMulticenter StudyComparative Study
In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. 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

27 authors.

Giorgia Teresa ManiscalcoNeurological Clinic and Stroke Unit and Multiple Sclerosis Center "A. Cardarelli" Hospital, Naples, Italy.
Maddalena SparacoSecond Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy.
Maria Di GregorioNeurology Unit, University Hospital "San Giovanni Di Dio E Ruggi D'Aragona", Salerno, Italy.
Giuseppina CafassoDepartment of Neurology, AORN San G. Moscati, Avellino, Italy.
Elisabetta SignorielloSecond Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy.
Felice RomanoNeurological and Stroke Unit-Multiple Sclerosis Center, CTO Hospital, AORN Ospedale Dei Colli, Naples, Italy.
Rosa IodiceDepartment of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
Roberta FantozziIRCCS Neuromed, Pozzilli, Isernia, Italy.
Paolo BellantonioIRCCS Neuromed, Pozzilli, Isernia, Italy.
Aurora ZanghiDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Leonardo SinisiDepartment of Neurology and MS Center, San Paolo Hospital, Naples, Italy.
Alessandro D'AmbrosioDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Vincenzo BusilloMs Center, Maria SS. Addolorata Hospital, ASL Salerno, Eboli, Italy.
Valentina ScaranoDepartment of Neurology, AORN San G. Moscati, Avellino, Italy.
Rocco CapuanoNeurology Unit, University Hospital "San Giovanni Di Dio E Ruggi D'Aragona", Salerno, Italy.
Luigi LavorgnaDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Michela WilliamsDepartment of Translational Medical Sciences, Section of Clinical Immunology, University of Naples "Federico II", Naples, Italy.
Antonio De MartinoNeurological Clinic and Stroke Unit and Multiple Sclerosis Center "A. Cardarelli" Hospital, Naples, Italy.
Maria Elena Di BattistaNeurological Clinic and Stroke Unit and Multiple Sclerosis Center "A. Cardarelli" Hospital, Naples, Italy.
Daniele Di Giulio CesareNeurological Clinic and Stroke Unit and Multiple Sclerosis Center "A. Cardarelli" Hospital, Naples, Italy.
Giacomo LusSecond Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy.
Emanuele CassanoDepartment of Neurology, "Ospedale del Mare", Naples, Italy.
Paola Sofia Di FilippoDepartment of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.
Grazia SibiliaDepartment of Neurology and MS Center, San Paolo Hospital, Naples, Italy.
Gianmarco AbbadessaSecond Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy.
Vincenzo AndreoneNeurological Clinic and Stroke Unit and Multiple Sclerosis Center "A. Cardarelli" Hospital, Naples, Italy.
Simona BonavitaSecond Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy. simona.bonavita@unicampania.it.ORCID http://orcid.org/0000-0002-8561-9720

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSphingosine-1-phosphate (S1P) receptor modulators, regulating the S1P/S1PR pathway, lead to lymphocyte sequestration in lymphoid organs, which results in peripheral lymphopenia. This study evaluates the degree of lymphopenia induced by S1P modulators in people with Multiple Sclerosis (MS): Ozanimod, Siponimod, Ponesimod, and Fingolimod.

methodsWe conducted a retrospective multicenter study across thirteen MS centers in Italy, including 191 MS patients (mean age 46.4 years; 61.3% women). Of these, 28.8% received Siponimod, 26.2% Ozanimod, 24.1% Fingolimod, and 20.9% Ponesimod. Lymphocyte counts were measured at baseline (T0), one month (T1), three months (T3), and six months (T6) post-treatment. Lymphopenia grades range from 0 (≥ 1.0 × 10^9 cells/L) to 4 (< 0.2 × 10^9 cells/L), according to Common Terminology Criteria for Adverse Events.

resultsAt T1, Ozanimod showed a significantly higher mean lymphocyte count than Siponimod and Fingolimod (p < 0.001), Ponesimod higher mean lymphocyte count than Siponimod (p = 0.006). The differences persisted between Ozanimod than Siponimod and Fingolimod at T3 (p = 0.01 and p = 0.04), and between Ponesimod and Siponimod at T6 (p = 0.03). Severe lymphopenia cases were significantly higher in Siponimod than in Ponesimod and Ozanimod, at T1 (p = 0.001 and p = 0.0001). The differences remained significant between Ozanimod and Siponimod, at T3 (p = 0.001), and between Ponesimod and Siponimod, Fingolimod and Ozanimod, at T6 (p = 0.001). Grade 4 lymphopenia was observed in Ozanimod and Siponimod at T3.

conclusionThis is the first real-world, head-to-head observational study comparing lymphopenia among different S1P modulators. Our results might assist in therapy choice depending on patients baseline hematological characteristics.

Indexed as

AzetidinesBenzyl CompoundsImmunosuppressive AgentsLymphopeniaMultiple SclerosisOxadiazolesSphingosine 1 Phosphate Receptor ModulatorsAdultFemaleFingolimod HydrochlorideHumansIndansItalyLymphocyte CountMaleMiddle AgedAzetidinesBenzyl CompoundsFingolimod HydrochlorideImmunosuppressive AgentsIndansOxadiazolesozanimodponesimodsiponimodSphingosine 1 Phosphate Receptor ModulatorsThiazolesLymphopeniaMultiple sclerosisSphingosine-1-phosphate receptor modulators

Identifiers

PMID40770143
PMCPMC12328508

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Registered trials

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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.