Evidence map›Paper›PMID 39264442›Full record

ArticleJournal of neurology2024

Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.

Ferdinando Clarelli, Andrea Corona, Kimmo Pääkkönen, Melissa Sorosina, Alen Zollo, Fredrik Piehl, Tomas Olsson, Pernilla Stridh, Maja Jagodic, Bernhard Hemmer and 14 more

Erratum issuedAbstract readMulticenter Study
In one paragraph

Article in Journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Frontiers in pharmacology · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Ferdinando Clarelli *Laboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
Andrea Corona *Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy.
Kimmo PääkkönenInstitute for Molecular Medicine Finland (FIMM), University of FI Helsinki, Helsinki, Finland.
Melissa SorosinaLaboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
Alen ZolloLaboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy.
Fredrik PiehlThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Tomas OlssonThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Pernilla StridhThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Maja JagodicThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Bernhard HemmerDepartment of Neurology, School of Medicine, Technical University of Munich, Klinikum Rechts Der Isar, Ismaninger Str. 22, Munich, Germany.
Christiane GasperiDepartment of Neurology, School of Medicine, Technical University of Munich, Klinikum Rechts Der Isar, Ismaninger Str. 22, Munich, Germany.
Adil HarroudDepartment of Neurology and Neurosurgery, McGill University, Montréal, QC, Canada.
Klementy ShchetynskyThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Alessandra MingioneLaboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy.
Elisabetta MasciaLaboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
Kaalindi MisraLaboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
Antonino GiordanoLaboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy.
Maria Laura Terzi MazzieriLaboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy.
Alberto PrioriCRC "Aldo Ravelli" for Experimental Brain Therapeutics, Department of Health Science, University of Milan, Milan, Italy.
Janna SaarelaInstitute for Molecular Medicine Finland (FIMM), University of FI Helsinki, Helsinki, Finland.
Ingrid KockumThe Karolinska Neuroimmunology & Multiple Sclerosis Centre, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Visionsgatan 18, 171 76, Stockholm, Sweden.
Massimo FilippiNeurology Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
Federica Esposito *Laboratory of Human Genetics of Neurological Disorders, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan, Italy. esposito.federica@hsr.it.
Filippo Giovanni Martinelli Boneschi *Laboratory of Precision Medicine of Neurological Diseases, Department of Health Science, University of Milan, Milan, Italy. filippo.martinelli@unimi.it.ORCID http://orcid.org/0000-0002-9955-1368

Funding

Horizon 2020 Framework Programme ID:733161Horizon 2020 Framework Programme MultipleMS
6 · The paper itself

Abstract

backgroundInter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ.

methodsMS patients from three different centers were included. Response to NTZ was dichotomized, nominating responders (R) relapse-free patients and non-responders (NR) all the others, over a follow-up of 4 years. Association analysis on ~ 4.7 M imputed autosomal common single-nucleotide polymorphisms (SNPs) was performed fitting logistic regression models, adjusted for baseline covariates, followed by meta-analysis at SNP and gene level. Finally, these signals were projected onto STRING interactome, to elicit modules and hub genes linked to response.

resultsOverall, 1834 patients were included: 119 from Italy (R = 94, NR = 25), 81 from Germany (R = 61, NR = 20), and 1634 from Sweden (R = 1349, NR = 285). The top-associated variant was rs11132400

conclusionThis GWAS, the largest pharmacogenomic study of response to NTZ, suggested MS-implicated genes and Wnt/β-catenin signaling pathway, an essential component for blood-brain barrier formation and maintenance, to be related to treatment response.

Indexed as

Genome-Wide Association StudyImmunologic FactorsNatalizumabPolymorphism, Single NucleotideAdultFemaleGermanyHumansItalyMaleMiddle AgedMultiple SclerosisPharmacogeneticsSwedenTreatment OutcomeImmunologic FactorsNatalizumabGRB2LRP6Multiple sclerosisNatalizumabPharmacogenomics

Identifiers

PMID39264442
PMCPMC11561017

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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 Socratic graph.