PMID- 35471586 OWN - NLM STAT- MEDLINE DCOM- 20220714 LR - 20221106 IS - 1432-1912 (Electronic) IS - 0028-1298 (Linking) VI - 395 IP - 8 DP - 2022 Aug TI - Natalizumab therapy in patients with pediatric-onset multiple sclerosis in Greece: clinical and immunological insights of time-long administration and future directions-a single-center retrospective observational study. PG - 933-943 LID - 10.1007/s00210-022-02238-y [doi] AB - Pediatric-onset multiple sclerosis (MS, POMS) accounts for 3-5% of all MS cases and is characterized by a highly inflammatory profile, often warranting treatment with high-efficacy agents. Our aim is to present real-world data of a series of 18 Hellenic POMS patients treated with natalizumab (NTZ) either as adolescents or as adults, after high disease activity has efficiently subsided. Clinical and imaging/laboratory data from 18 POMS patients who have received at least one NTZ infusion were selected in this single-center retrospective observational study. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Eighteen patients with a mean age of disease onset of 15.3 +/- 2.4 years were treated with NTZ with a mean of 51.7 +/- 46.4 infusions, 6 as adolescents and 12 as adults. 22.2% were treatment naive. At the end of the observational period, patients of both groups remained relapse-free, with no radiological activity and significantly reduced disability accumulation. No evidence of disease activity (NEDA)-3 status was achieved in 66.7% of all patients, 58.3% in the adult-treated, and 83.3% in the adolescent-treated POMS patients. NTZ was generally well tolerated. Only 5 adverse events were observed, in 3 patients who were carriers of the HLA-DRB1*15 (HLA-DRB1*15/HLA-DRB1*11 and HLA-DRB1*15/HLA-DRB1*13 genotypes), 1 homozygous for the HLA-DRB1*03 allele and 1 heterozygous for HLA-DRB1*04 and HLA-DRB1*16 alleles. NTZ is highly efficacious and mostly safe for POMS patients with high disease activity in all age groups. The role of immunogenetics in personalized patient evaluation and treatment needs to be further investigated. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Gontika, Maria AU - Gontika M AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Skarlis, Charalampos AU - Skarlis C AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Markoglou, Nikolaos AU - Markoglou N AD - Immunogenetics Laboratory, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sophias, 74, 115 28, Athens, Greece. FAU - Tzanetakos, Dimitrios AU - Tzanetakos D AD - Multiple Sclerosis and Demyelinating Diseases Unit, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece. FAU - Vakrakou, Aglaia AU - Vakrakou A AD - Multiple Sclerosis and Demyelinating Diseases Unit, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece. FAU - Toulas, Panagiotis AU - Toulas P AD - Research Unit of Radiology, 2nd Department of Radiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece. FAU - Koutsis, George AU - Koutsis G AD - Multiple Sclerosis and Demyelinating Diseases Unit, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece. FAU - Evangelopoulos, Maria-Eleptheria AU - Evangelopoulos ME AD - Multiple Sclerosis and Demyelinating Diseases Unit, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece. FAU - Pons, Roser AU - Pons R AD - 1st Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece. FAU - Dardiotis, Efthymios AU - Dardiotis E AD - Department of Neurology, University Hospital of Larissa, 41110, Larissa, Greece. FAU - Chrousos, George AU - Chrousos G AD - University Research Institute of Maternal and Child Health and Precision Medicine and UNESCO Chair On Adolescent Health Care, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, 11527, Athens, Greece. FAU - Dalakas, Marinos AU - Dalakas M AD - Neuroimmunology Unit, Dept 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, National and Kapodistrian University of Athens, Aeginition University Hospital, 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, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sophias, 74, 115 28, Athens, Greece. managnost@med.uoa.gr. AD - Multiple Sclerosis and Demyelinating Diseases Unit, 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Athens, Greece. managnost@med.uoa.gr. AD - 1st Department of Neurology, Medical School, National and Kapodistrian University of Athens, Aeginition University Hospital, Vas. Sophias, 74, 115 28, Athens, Greece. managnost@med.uoa.gr. LA - eng PT - Journal Article PT - Observational Study DEP - 20220426 PL - Germany TA - Naunyn Schmiedebergs Arch Pharmacol JT - Naunyn-Schmiedeberg's archives of pharmacology JID - 0326264 RN - 0 (HLA-DRB1 Chains) RN - 0 (Natalizumab) SB - IM MH - Adolescent MH - Child MH - Greece MH - HLA-DRB1 Chains/genetics MH - Humans MH - *Multiple Sclerosis/drug therapy/genetics MH - *Natalizumab/therapeutic use MH - Retrospective Studies OTO - NOTNLM OT - HLA OT - JCV OT - Multiple sclerosis OT - Natalizumab OT - Outcome OT - Therapy EDAT- 2022/04/27 06:00 MHDA- 2022/07/15 06:00 CRDT- 2022/04/26 12:53 PHST- 2021/10/29 00:00 [received] PHST- 2022/04/01 00:00 [accepted] PHST- 2022/04/27 06:00 [pubmed] PHST- 2022/07/15 06:00 [medline] PHST- 2022/04/26 12:53 [entrez] AID - 10.1007/s00210-022-02238-y [pii] AID - 10.1007/s00210-022-02238-y [doi] PST - ppublish SO - Naunyn Schmiedebergs Arch Pharmacol. 2022 Aug;395(8):933-943. doi: 10.1007/s00210-022-02238-y. Epub 2022 Apr 26.