PMID- 34596776 OWN - NLM STAT- MEDLINE DCOM- 20220315 LR - 20220315 IS - 1590-3478 (Electronic) IS - 1590-1874 (Linking) VI - 43 IP - 4 DP - 2022 Apr TI - 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. PG - 2641-2649 LID - 10.1007/s10072-021-05623-2 [doi] AB - 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-naive 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-naive patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations. CI - (c) 2021. Fondazione Societa Italiana di Neurologia. FAU - Gontika, Maria AU - Gontika M AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Skarlis, Charalampos AU - Skarlis C AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Markoglou, Nikolaos AU - Markoglou N AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Evangelopoulos, Maria-Eleftheria AU - Evangelopoulos ME AD - 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. FAU - Velonakis, George AU - Velonakis G AD - Research Unit of Radiology, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. FAU - Chrousos, George P AU - Chrousos GP AD - 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. FAU - Dalakas, Marinos AU - Dalakas M AD - Neuroimmunology Unit, Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece. AD - Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA. FAU - Stefanis, Leonidas AU - Stefanis L AD - 1st Department of Neurology, Medical School, Aeginition University Hospital, National and Kapodistrian University of Athens, NKUA, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Anagnostouli, Maria AU - Anagnostouli M AUID- ORCID: 0000-0001-8934-670X AD - 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. AD - 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. AD - 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. LA - eng PT - Journal Article DEP - 20211001 PL - Italy TA - Neurol Sci JT - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology JID - 100959175 RN - 0 (HLA-DRB1 Chains) RN - 0 (Immunosuppressive Agents) RN - 0 (Natalizumab) RN - G926EC510T (Fingolimod Hydrochloride) SB - IM MH - Adolescent MH - Adult MH - Child MH - Fingolimod Hydrochloride/therapeutic use MH - HLA-DRB1 Chains MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - *Multiple Sclerosis/diagnostic imaging/drug therapy/genetics MH - *Multiple Sclerosis, Relapsing-Remitting/drug therapy MH - Natalizumab/therapeutic use OTO - NOTNLM OT - Fingolimod OT - HLA OT - Multiple sclerosis OT - Neuroimmunology OT - Pediatric OT - Therapeutics EDAT- 2021/10/02 06:00 MHDA- 2022/03/16 06:00 CRDT- 2021/10/01 12:27 PHST- 2021/08/21 00:00 [received] PHST- 2021/09/17 00:00 [accepted] PHST- 2021/10/02 06:00 [pubmed] PHST- 2022/03/16 06:00 [medline] PHST- 2021/10/01 12:27 [entrez] AID - 10.1007/s10072-021-05623-2 [pii] AID - 10.1007/s10072-021-05623-2 [doi] PST - ppublish SO - Neurol Sci. 2022 Apr;43(4):2641-2649. doi: 10.1007/s10072-021-05623-2. Epub 2021 Oct 1.