Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts.

Autor:	Sharmin S; CORe, Department of Medicine, University of Melbourne, L4 East, Grattan St, Melbourne, VIC, 3050, Australia., Lefort M; Rennes University, EHESP, REPERES, EA, 7449, Rennes, France.; Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, France., Andersen JB; The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Leray E; Rennes University, EHESP, REPERES, EA, 7449, Rennes, France.; Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), Rennes, France., Horakova D; Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic., Havrdova EK; Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic., Alroughani R; Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait., Izquierdo G; Hospital Universitario Virgen Macarena, Seville, Spain., Ozakbas S; Dokuz Eylul University, Konak, Izmir, Turkey., Patti F; Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.; Multiple Sclerosis Center, University of Catania, Catania, Italy., Onofrj M; Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy., Lugaresi A; IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.; Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italia., Terzi M; Medical Faculty, 19 Mayis University, Samsun, Turkey., Grammond P; CISSS Chaudière-Appalache, Levis, Canada., Grand'Maison F; Neuro Rive-Sud, Greenfield Park, Quebec, Canada., Yamout B; Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon., Prat A; CHUM MS Center and Universite de Montreal, Montreal, Canada., Girard M; CHUM MS Center and Universite de Montreal, Montreal, Canada., Duquette P; CHUM MS Center and Universite de Montreal, Montreal, Canada., Boz C; KTU Medical Faculty Farabi Hospital, Trabzon, Turkey., Trojano M; Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy., McCombe P; University of Queensland, Brisbane, Australia.; Royal Brisbane and Women's Hospital, Brisbane, Australia., Slee M; College of Medicine and Public Health, Flinders University, Adelaide, Australia., Lechner-Scott J; School of Medicine and Public Health, University Newcastle, Newcastle, Australia.; Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, Australia., Turkoglu R; Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey., Sola P; Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy., Ferraro D; Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy., Granella F; Department of Medicine and Surgery, University of Parma, Parma, Italy.; Department of Emergency and General Medicine, Parma University Hospital, Parma, Italy., Prevost J; CSSS Saint-Jérôme, Saint-Jerome, Canada., Maimone D; Neurology Unit, Garibaldi Hospital, Catania, Italy., Skibina O; Department of Neuroscience, Monash University, Melbourne, Australia.; Department of Neurology, The Alfred Hospital, Melbourne, Australia., Buzzard K; Department of Neurology, The Alfred Hospital, Melbourne, Australia.; Central Clinical School, Monash University, Melbourne, Australia., Van der Walt A; Department of Neurology, The Alfred Hospital, Melbourne, Australia.; Central Clinical School, Monash University, Melbourne, Australia., Van Wijmeersch B; Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium., Csepany T; Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary., Spitaleri D; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy., Vucic S; Neurophysiology Department, Westmead Hospital, Sydney, Australia., Casey R; Université de Lyon, Université, Claude Bernard Lyon 1, F-69000, Lyon, France.; Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, Lyon, France.; Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, 69003, Lyon, France.; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, 69677, Bron, France., Debouverie M; Department of Neurology, Nancy University Hospital, Nancy, France.; Université de Lorraine, APEMAC, 54000, Nancy, France., Edan G; CHU Pontchaillou, CIC1414 INSERM, 35000, Rennes, France., Ciron J; Department of Neurology, CHU de Toulouse, Hôpital Pierre-Paul Riquet, CRC-SEP, 31059, Toulouse Cedex 9, France., Ruet A; Neurocentre Magendie, Université de Bordeaux, 33000, Bordeaux, France.; INSERM U1215, Neurocentre Magendie, 33000, Bordeaux, France.; Department of Neurology, CHU de Bordeaux, CIC Bordeaux CIC1401, 33000, Bordeaux, France., De Sèze J; Department of Neurology and Clinical Investigation Center, CHU de Strasbourg, CIC 1434, INSERM 1434, 67000, Strasbourg, France., Maillart E; Département de neurologie, Hôpital Pitié-Salpêtrière, APHP, Paris, France.; Centre de Ressources et de Compétences SEP, Paris, France., Zephir H; CHU Lille, CRCSEP Lille, Univ Lille, U1172, 59000, Lille, France., Labauge P; MS Unit, CHU de Montpellier, 34295, Montpellier Cedex 5, France.; University of Montpellier (MUSE), 34000, Montpellier, France., Defer G; Department of Neurology, CHU de Caen, MS Expert Centre, Normandy University, avenue de la Côte-de-Nacre, 14033, Caen, France., Lebrun-Frénay C; CRCSEP Nice, UR2CA, Université Nice Cote d'Azur, Hopital Pasteur2, 06002, Nice, France., Moreau T; Department of Neurology, CHU de Dijon, EA4184, 21000, Dijon, France., Berger E; CHU de Besançon, Service de Neurologie 25 030, Besançon, France., Clavelou P; Department of Neurology, CHU Clermont-Ferrand, 63000, Clermont-Ferrand, France.; Université Clermont Auvergne, Inserm, Neuro-Dol, 63000, Clermont-Ferrand, France., Pelletier J; Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, 13005, Marseille, France., Stankoff B; Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225, Paris, France.; Department of Neurology, AP-HP, Saint-Antoine Hospital, 75000, Paris, France., Gout O; Department of Neurology, Fondation Rotschild, 75000, Paris, France., Thouvenot E; Department of Neurology, Nimes University Hospital, 30029, Nimes Cedex 9, France.; Institut de Génomique Fonctionnelle, UMR5203, INSERM 1191, Univ. Montpellier, 34094, Montpellier Cedex 5, France., Heinzlef O; Department of Neurology, Hôpital de Poissy, 78300, Poissy, France., Al-Khedr A; Department of Neurology, CHU d'Amiens, 80000, Amiens, France., Bourre B; Department of Neurology, CHU de Rouen, 76000, Rouen, France., Casez O; Department of Neurology, CHU Grenoble Alpes, La Tronche, 38700, Grenoble, France., Cabre P; Department of Neurology, CHU de la Martinique, 97200, Fort-de-France, France., Montcuquet A; Department of Neurology, CHU de Limoges, Hôpital Dupuytren, 87000, Limoges, France., Wahab A; Department of Neurology, APHP, Hôpital Henri Mondor, 94000, Créteil, France., Camdessanché JP; Department of Neurology, CHU de Saint-Étienne, Hôpital Nord, 42000, Saint-Étienne, France., Maurousset A; CRC SEP and Department of Neurology, CHU de Tours, Hôpital Bretonneau, 37000, Tours, France., Patry I; Department of Neurology, Hôpital Sud Francilien, 91160, Corbeil Essonnes, France., Hankiewicz K; Department of Neurology, Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, 93200, Saint-Denis, France., Pottier C; Department of Neurology, CH de Pontoise, Hôpital René Dubos, 95300, Pontoise, France., Maubeuge N; Department of Neurology, CHU La Milétrie, Hôpital Jean Bernard, 86000, Poitiers, France., Labeyrie C; Department of Neurology, CHU Bicêtre, 94275, Le Kremlin Bicêtre, France., Nifle C; Department of Neurology, Centre Hospitalier de Versailles, 78150, Le Chesnay, France., Laplaud D; CHU de Nantes, Service de Neurologie & CIC015 INSERM, 44093, Nantes, France.; CRTI-Inserm U1064, 44000, Nantes, France., Koch-Henriksen N; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark., Sellebjerg FT; Department of Neurology, The Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Soerensen PS; Department of Neurology, The Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Pfleger CC; Multiple Sclerosis Unit, Department of Neurology, Aalborg University Hospital, Aalborg, Denmark., Rasmussen PV; Aarhus University Hospital, Neurology, PPJ Boulevard, 8200, Aarhus N, Denmark., Jensen MB; Department of Neurology, University Hospital of Northern Sealand, Helsingør, Denmark., Frederiksen JL; Department of Neurology, Rigshospitalet Glostrup, Copenhagen, Denmark.; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Bramow S; Department of Neurology, Danish Multiple Sclerosis Centre, Copenhagen University Hospital, Rigshospitalet in Glostrup, 2600, Glostrup, Denmark., Mathiesen HK; Department of Neurology, Copenhagen University Hospital Herlev, Herlev, Denmark., Schreiber KI; Department of Neurology, The Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Magyari M; The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.; Department of Neurology, The Danish Multiple Sclerosis Center, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark., Vukusic S; Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, Lyon, France.; Centre des Neurosciences de Lyon, Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, 69003, Lyon, France.; Université Claude Bernard Lyon 1, Faculté de médecine Lyon Est, F-69000, Lyon, France., Butzkueven H; Department of Neurology, The Alfred Hospital, Melbourne, Australia.; Central Clinical School, Monash University, Melbourne, Australia.; Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Australia., Kalincik T; CORe, Department of Medicine, University of Melbourne, L4 East, Grattan St, Melbourne, VIC, 3050, Australia. tomas.kalincik@unimelb.edu.au.; MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. tomas.kalincik@unimelb.edu.au.
Jazyk:	angličtina
Zdroj:	CNS drugs [CNS Drugs] 2021 Nov; Vol. 35 (11), pp. 1217-1232. Date of Electronic Publication: 2021 Sep 18.
DOI:	10.1007/s40263-021-00860-7
Abstrakt:	Introduction: Natalizumab has proved to be more effective than fingolimod in reducing disease activity in relapsing-remitting multiple sclerosis (RRMS). Whether this association is universal for all patient groups remains to be determined. Objective: The aim of this study was to compare the relative effectiveness of natalizumab and fingolimod in RRMS subgroups defined by the baseline demographic and clinical characteristics of interest. Methods: Patients with RRMS who were given natalizumab or fingolimod were identified in a merged cohort from three international registries. Efficacy outcomes were compared across subgroups based on patients' sex, age, disease duration, Expanded Disability Status Scale (EDSS) score, and disease and magnetic resonance imaging (MRI) activity 12 months prior to treatment initiation. Study endpoints were number of relapses (analyzed with weighted negative binomial generalized linear model) and 6-month confirmed disability worsening and improvement events (weighted Cox proportional hazards model), recorded during study therapy. Each patient was weighted using inverse probability of treatment weighting based on propensity score. Results: A total of 5148 patients (natalizumab 1989; fingolimod 3159) were included, with a mean ± standard deviation age at baseline of 38 ± 10 years, and the majority (72%) were women. The median on-treatment follow-up was 25 (quartiles 15-41) months. Natalizumab was associated with fewer relapses than fingolimod (incidence rate ratio [IRR]; 95% confidence interval [CI]) in women (0.76; 0.65-0.88); in those aged ≤ 38 years (0.64; 0.54-0.76); in those with disease duration ≤ 7 years (0.63; 0.53-0.76); in those with EDSS score < 4 (0.75; 0.64-0.88), < 6 (0.80; 0.70-0.91), and ≥ 6 (0.52; 0.31-0.86); and in patients with pre-baseline relapses (0.74; 0.64-0.86). A higher probability of confirmed disability improvement on natalizumab versus fingolimod (hazard ratio [HR]; 95% CI) was observed among women (1.36; 1.10-1.66); those aged > 38 years (1.34; 1.04-1.73); those with disease duration > 7 years (1.33; 1.01-1.74); those with EDSS score < 6 (1.21; 1.01-1.46) and ≥ 6 (1.93; 1.11-3.34); and patients with no new MRI lesion (1.73; 1.19-2.51). Conclusions: Overall, in women, younger patients, those with shorter disease durations, and patients with pre-treatment relapses, natalizumab was associated with a lower frequency of multiple sclerosis relapses than fingolimod. It was also associated with an increased chance of recovery from disability among most patients, particularly women and those with no recent MRI activity. (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze:	MEDLINE
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