Maria Gontika1, Charalampos Skarlis1, Nikolaos Markoglou1, Maria-Eleftheria Evangelopoulos2, George Velonakis3, George P Chrousos4, Marinos Dalakas5,6, Leonidas Stefanis7, Maria Anagnostouli8,9,10. 1. Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. 2. 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. 3. Research Unit of Radiology, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 4. 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. 5. Neuroimmunology Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece. 6. Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. 7. 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, NKUA, Vas. Sophias, 74, 115 28, Athens, Greece. 8. 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. 9. 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. 10. 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.
Abstract
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: Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. 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: 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)+NK cell counts in immunophenotyping assays. 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.
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: Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. 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: 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)+NK cell counts in immunophenotyping assays. 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.
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