title: Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis.
abstract: In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i.e. switching from IFNB to GA or viceversa (in the case of non-responders) or starting high-dose IFNB (in the case of highly active treatment-naïves). Propensity score matching in a 1:1:1 ratio was used to select only patients with similar baseline characteristics, retaining 330 and 120 patients in dataset A and B, respectively. In dataset A, the 24-month proportion with NEDA-3 was greater in both NTZ group (67%) and FNG group (42%) than in INJ group (35%) (p ≤ 0.016); however, NTZ was superior to FNG in promoting the attainment of NEDA-3 status (p = 0.034). In dataset B, the 24-month proportion with NEDA-3 was greater in NTZ group (75%) and FNG group (67%) than in INJ group (40%), but the small cohort sizes most likely prevented the detection of any statistically significant difference. Our study provides real-world evidence that NTZ was more effective than both FNG and INJ in non-responders, while it could seem that, in highly active treatment-naïves, NTZ was as effective as FNG and both were superior to INJ.
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy. luca.prosperini@uniroma1.it.
authors.forename: Luca
authors.identifier: http://orcid.org/0000-0003-3237-6267
authors.initials: L
authors.lastname: Prosperini
authors.affiliation: Department of Neuroscience, Reproductive Science and Odontostomatology, MS Clinical Care and Research Center, Federico II University, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccà
authors.affiliation: MS Centre, Spedali Civili di Brescia, Montichiari, BS, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Cordioli
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cortese
authors.affiliation: Department of Systems Medicine, MS Clinical and Research Center, Tor Vergata University, Rome, Italy.|Unit of Neurology and of Neurorehabilitation, IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Buttari
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Pontecorvo
authors.affiliation: Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Bianco
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.|Department of Neurosciences, S. Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ruggieri
authors.affiliation: Department of Neurosciences, S. Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Shalom
authors.initials: S
authors.lastname: Haggiag
authors.affiliation: Department of Neuroscience, Reproductive Science and Odontostomatology, MS Clinical Care and Research Center, Federico II University, Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Brescia Morra
authors.affiliation: MS Centre, Spedali Civili di Brescia, Montichiari, BS, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
authors.affiliation: Department of Systems Medicine, MS Clinical and Research Center, Tor Vergata University, Rome, Italy.|Unit of Neurology and of Neurorehabilitation, IRCCS Neuromed, Pozzilli, IS, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.affiliation: Unit of Neurology, S. Filippo Neri Hospita - ASL Roma 1, Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Di Battista
authors.affiliation: Unit of Neurology, S. Filippo Neri Hospita - ASL Roma 1, Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferraro
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: Francia
authors.affiliation: Department of Neurosciences, S. Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Galgani
authors.affiliation: Department of Neurosciences, S. Camillo Forlanini Hospital, Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Millefiorini
authors.affiliation: Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Mirabella
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Viale dell'Università, 30, 00185, Rome, Italy.|S. Andrea Hospital, Rome, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000008:administration & dosage*; D057216:Propensity Score; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012646:Self Administration; D062606:Tertiary Care Centers; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab; D000068876:Fingolimod Hydrochloride
keywords: Disease-modifying drugs; Multiple sclerosis; NEDA; Propensity score