Tim Spelman1, Tomas Kalincik1, Vilija Jokubaitis1, Annie Zhang1, Fabio Pellegrini1, Heinz Wiendl1, Shibeshih Belachew1, Robert Hyde1, Freek Verheul1, Alessandra Lugaresi1, Eva Havrdová1, Dana Horáková1, Pierre Grammond1, Pierre Duquette1, Alexandre Prat1, Gerardo Iuliano1, Murat Terzi1, Guillermo Izquierdo1, Raymond M M Hupperts1, Cavit Boz1, Eugenio Pucci1, Giorgio Giuliani1, Patrizia Sola1, Daniele L A Spitaleri1, Jeannette Lechner-Scott1, Roberto Bergamaschi1, François Grand'Maison1, Franco Granella1, Ludwig Kappos1, Maria Trojano1, Helmut Butzkueven1. 1. Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital (TS, TK, VJ, HB), University of Melbourne, Australia; Biogen Idec Inc. (AZ, FP, SB, RH), Cambridge, MA; Department of Neurology (HW), University of Münster, Germany; Groene Hart Ziekenhuis (FV), Gouda, the Netherlands; MS Center, Department of Neuroscience, Imaging and Clinical Sciences (AL), University "G. d'Annunzio," Chieti, Italy; MS Center, Department of Neurology, First Medical Faculty (EH, DH), Charles University, Prague, Czech Republic; Center de Réadaptation Déficience Physique Chaudière-Appalache (PG), Levis; Hôpital Notre Dame (PD, AP), Montreal, Canada; Ospedali Riuniti di Salerno (G. Iuliano), Salerno, Italy; 19 Mayis University (M. Terzi), Medical Faculty, Turkey; Hospital Universitario Virgen Macarena (G. Izquierdo), Sevilla, Spain; Orbis Medical Centre (RMMH), Sittard-Geleen, the Netherlands; KTU Medical Faculty Farabi Hospital (CB), Trabzon, Turkey; Neurology Unit (EP, GG), ASUR Marche-AV3, Macerata; Nuovo Ospedale Civile S. Agostino (PS), Modena; AORN San Giuseppe Moscati (DLAS), Avellino, Italy; John Hunter Hospital (JL-S), Newcastle, Australia; Neurological Institute IRCCS Mondino (RB), Pavia, Italy; Neuro Rive-Sud (F. Grand'Maison), Hôpital Charles LeMoyne, Quebec, Canada; University of Parma (F. Granella), Italy; Department of Neurology (LK), University Hospital Basel, Switzerland; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; and Department of Neurology (HB), Eastern Health, Monash University, Australia.
Abstract
BACKGROUND: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries. METHODS: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n = 366/group) and subgroups with higher baseline disease activity. RESULTS: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) (p [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; p < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; p = 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups. CONCLUSIONS: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA.
BACKGROUND: We compared efficacy and treatment persistence in treatment-naive patients with relapsing-remitting multiple sclerosis (RRMS) initiating natalizumab compared with interferon-β (IFN-β)/glatiramer acetate (GA) therapies, using propensity score-matched cohorts from observational multiple sclerosis registries. METHODS: The study population initiated IFN-β/GA in the MSBase Registry or natalizumab in the Tysabri Observational Program, had ≥3 months of on-treatment follow-up, and had active RRMS, defined as ≥1 gadolinium-enhancing lesion on cerebral MRI at baseline or ≥1 relapse within the 12 months prior to baseline. Baseline demographics and disease characteristics were balanced between propensity-matched groups. Annualized relapse rate (ARR), time to first relapse, treatment persistence, and disability outcomes were compared between matched treatment arms in the total population (n = 366/group) and subgroups with higher baseline disease activity. RESULTS: First-line natalizumab was associated with a 68% relative reduction in ARR from a mean (SD) of 0.63 (0.92) on IFN-β/GA to 0.20 (0.63) (p [signed-rank] < 0.0001), a 64% reduction in the rate of first relapse (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.28-0.47; p < 0.001), and a 27% reduction in the rate of discontinuation (HR 0.73, 95% CI 0.58-0.93; p = 0.01), compared with first-line IFN-β/GA therapy. Confirmed disability progression and area under the Expanded Disability Status Scale-time curve analyses were not significant. Similar relapse and treatment persistence results were observed in each of the higher disease activity subgroups. CONCLUSIONS: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse and treatment persistence outcomes compared to first-line IFN-β/GA. This needs to be balanced against the risk of progressive multifocal leukoencephalopathy in natalizumab-treated patients. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that first-line natalizumab for RRMS improves relapse rates and treatment persistence outcomes compared to first-line IFN-β/GA.
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