Fingolimod as a first- or second-line treatment in a mini-series of young Hellenic patients with adolescent-onset multiple sclerosis: focus on immunological data.

Adolescent Adult Child Fingolimod Hydrochloride / therapeutic use HLA-DRB1 Chains Humans Immunosuppressive Agents / therapeutic use Multiple Sclerosis / diagnostic imaging Multiple Sclerosis, Relapsing-Remitting / drug therapy Natalizumab / therapeutic use
Fingolimod HLA Multiple sclerosis Neuroimmunology Pediatric Therapeutics

Journal

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
ISSN: 1590-3478
Titre abrégé: Neurol Sci
Pays: Italy
ID NLM: 100959175

Informations de publication

Date de publication:
Apr 2022
Historique:
received: 21 08 2021
accepted: 17 09 2021
pubmed: 2 10 2021
medline: 16 3 2022
entrez: 1 10 2021
Statut: ppublish

Résumé

Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS. Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56) Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.

Sections du résumé

BACKGROUND BACKGROUND
Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS.
OBJECT OBJECTIVE
Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece.
METHODS METHODS
Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques.
RESULTS RESULTS
Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56)
CONCLUSIONS CONCLUSIONS
Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.

Identifiants

DOI: 10.1007/s10072-021-05623-2 PMID: 34596776
pubmed: 34596776
doi: 10.1007/s10072-021-05623-2
pii: 10.1007/s10072-021-05623-2
doi:

Substances chimiques

HLA-DRB1 Chains 0
Immunosuppressive Agents 0
Natalizumab 0
Fingolimod Hydrochloride G926EC510T

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2641-2649

Informations de copyright

© 2021. Fondazione Società Italiana di Neurologia.

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Auteurs

Maria Gontika (M)

Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece.

Charalampos Skarlis (C)

Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece.

Nikolaos Markoglou (N)

Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece.

Maria-Eleftheria Evangelopoulos (ME)

Multiple Sclerosis and Demyelinating Diseases Unit, 1st, Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece.

George Velonakis (G)

Research Unit of Radiology, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

George P Chrousos (GP)

University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair On Adolescent Health Care, Aghia Sophia Children's Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece.

Marinos Dalakas (M)

Neuroimmunology Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece.
Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.

Leonidas Stefanis (L)

1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, NKUA, Vas. Sophias, 74, 115 28, Athens, Greece.

Maria Anagnostouli (M)

Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. managnost@med.uoa.gr.
Multiple Sclerosis and Demyelinating Diseases Unit, 1st, Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. managnost@med.uoa.gr.
1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, NKUA, Vas. Sophias, 74, 115 28, Athens, Greece. managnost@med.uoa.gr.
ORCID: 0000-0001-8934-670X

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Fingolimod as a first- or second-line...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Fingolimod as a first- or second-line...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Fingolimod as a first- or second-line...
questionsmedicales.fr › Composés chimiques organiques › Amines › Aminoalcools › Sphingosine › Chlorhydrate de fingolimod › Fingolimod as a first- or second-line...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes HLA › Antigènes HLA-D › Antigènes HLA-DR › Chaines bêta des antigènes HLA-DR › Chaines HLA-DRB1 › Fingolimod as a first- or second-line...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Fingolimod as a first- or second-line...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immunosuppresseurs › Fingolimod as a first- or second-line...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Fingolimod as a first- or second-line...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Sclérose en plaques récurrente-rémittente › Fingolimod as a first- or second-line...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Natalizumab › Fingolimod as a first- or second-line...