Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

Autor: Filippi M; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. filippi.massimo@hsr.it.; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. filippi.massimo@hsr.it.; Vita-Salute San Raffaele University, Milan, Italy. filippi.massimo@hsr.it.; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. filippi.massimo@hsr.it.; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy. filippi.massimo@hsr.it., Pagani E; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy., Turrini R; Medical Department, Novartis Farma S.P.A, Milan, Italy., Bartezaghi M; Medical Department, Novartis Farma S.P.A, Milan, Italy., Brescia Morra V; Multiple Sclerosis Clinical Care and Research Center, Department of Neuroscience (NSRO), Federico II University, Naples, Italy., Borriello G; Centro Di Riferimento Regionale per la Sclerosi Multipla, Ospedale San Pietro Fatebenefratelli, Rome, Italy., Torri Clerici V; IRCCS Istituto Neurologico C. Besta, Neuroimmunology Unit, Milan, Italy., Mirabella M; Multiple Sclerosis Center, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, Rome, Italy.; Centro Di Ricerca Sclerosi Multipla (CERSM), Università Cattolica del Sacro Cuore, Rome, Italy., Pasquali L; Neurology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy., Patti F; Dipartimento di Scienze Mediche e Chirurgiche e Tecnologie Avanzate, GF Ingrassia, Centro Sclerosi Multipla, Università Di Catania, Sez. Neuroscienze, Catania, Italy., Totaro R; Demyelinating Disease Center, San Salvatore Hospital, L'Aquila, Italy., Gallo P; Department of Neurosciences, Multiple Sclerosis Centre-Veneto Region (CeSMuV), University Hospital of Padua, Padua, Italy., Rocca MA; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.; Vita-Salute San Raffaele University, Milan, Italy.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Sep; Vol. 271 (9), pp. 6181-6196. Date of Electronic Publication: 2024 Jul 29.
DOI: 10.1007/s00415-024-12590-z
Abstrakt: Background and Objectives: In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients.
Methods: The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24 months: (1) no new/enlarging T 2 -hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T 2 -hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T 2 -FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs).
Results: At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod.
Discussion: By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.
(© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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