TY - JOUR
T1 - Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis
T2 - A Subgroup Analysis From Three International Cohorts
AU - Sharmin, Sifat
AU - Lefort, Mathilde
AU - Andersen, Johanna Balslev
AU - Leray, Emmanuelle
AU - Horakova, Dana
AU - Havrdova, Eva Kubala
AU - Alroughani, Raed
AU - Izquierdo, Guillermo
AU - Ozakbas, Serkan
AU - Patti, Francesco
AU - Onofrj, Marco
AU - Lugaresi, Alessandra
AU - Terzi, Murat
AU - Grammond, Pierre
AU - Grand’Maison, Francois
AU - Yamout, Bassem
AU - Prat, Alexandre
AU - Girard, Marc
AU - Duquette, Pierre
AU - Boz, Cavit
AU - Trojano, Maria
AU - McCombe, Pamela
AU - Slee, Mark
AU - Lechner-Scott, Jeannette
AU - Turkoglu, Recai
AU - Sola, Patrizia
AU - Ferraro, Diana
AU - Granella, Franco
AU - Prevost, Julie
AU - Maimone, Davide
AU - Skibina, Olga
AU - Buzzard, Katherine
AU - Van der Walt, Anneke
AU - Van Wijmeersch, Bart
AU - Csepany, Tunde
AU - Spitaleri, Daniele
AU - Vucic, Steve
AU - Casey, Romain
AU - Debouverie, Marc
AU - Edan, Gilles
AU - Ciron, Jonathan
AU - Ruet, Aurélie
AU - De Sèze, Jérôme
AU - Maillart, Elisabeth
AU - Zephir, Hélène
AU - Labauge, Pierre
AU - Defer, Gilles
AU - Lebrun-Frénay, Christine
AU - Moreau, Thibault
AU - Berger, Eric
AU - Clavelou, Pierre
AU - Pelletier, Jean
AU - Stankoff, Bruno
AU - Gout, Olivier
AU - Thouvenot, Eric
AU - Heinzlef, Olivier
AU - Al-Khedr, Abullatif
AU - Bourre, Bertrand
AU - Casez, Olivier
AU - Cabre, Philippe
AU - Montcuquet, Alexis
AU - Wahab, Abir
AU - Camdessanché, Jean Philippe
AU - Maurousset, Aude
AU - Patry, Ivania
AU - Hankiewicz, Karolina
AU - Pottier, Corinne
AU - Maubeuge, Nicolas
AU - Labeyrie, Céline
AU - Nifle, Chantal
AU - Laplaud, David
AU - Koch-Henriksen, Niels
AU - Sellebjerg, Finn Thorup
AU - Soerensen, Per Soelberg
AU - Pfleger, Claudia Christina
AU - Rasmussen, Peter Vestergaard
AU - Jensen, Michael Broksgaard
AU - Frederiksen, Jette Lautrup
AU - Bramow, Stephan
AU - Mathiesen, Henrik Kahr
AU - Schreiber, Karen Ingrid
AU - Magyari, Melinda
AU - Vukusic, Sandra
AU - Butzkueven, Helmut
AU - Kalincik, Tomas
AU - Danish Multiple Sclerosis Registry, OFSEP and the MSBase investigators
N1 - Funding Information:
The Clinical Outcomes Research unit at the University of Melbourne received funding from the National Health and Medical Research Council (Grant numbers 1140766, 1129789, and 1157717) to support this study. The MSBase Foundation is a not-for-profit organization that receives support from Merck, Biogen, Novartis, Roche, Bayer Schering, Sanofi Genzyme, and Teva Pharmaeutical Industries. OFSEP was supported by a grant provided by the French State and handled by the "Agence Nationale de la Recherche," within the framework of the "Investments for the Future" program, under the reference ANR-10-COHO-002, by the Eugène Devic EDMUS Foundation against multiple sclerosis and by the ARSEP Foundation. The Danish Multiple Sclerosis Registry did not receive any funding to collaborate in this study.
Funding Information:
Authors of the MSBase registry: The following authors have received speaker honoraria, advisory board or steering committee fees, research support, and/or conference travel support from Actelion (EKH), Almirall (GI, FP, MT), Bayer (RA, FP, AL, MT, CB, MT, MS, JLS, BVW, TC, DS), BioCSL (KB, TK), Biogen (DH, EKH, RA, GI, FP, AL, PG, FGM, MG, PD, CB, MT, MS, JLS, PS, DF, FG, JP, BVW, TC, HB, TK), Canadian Multiple sclerosis society (PG, PD), Canadian Institutes of Health Research (MG, PD), Celgene (EKH, FP, TK), Czech Ministry of Education (DH, EKH), Fondazione Italiana Sclerosi Multipla (FP, AL), Grifols (KB), Genzyme-Sanofi (DH, EKH, RA, GI, FP, AL, MT, PG, FGM, MG, PD, CB, MT, MS, JLS, PS, DF, FG, JP, BVW, TC, DS, HB, TK), GSK (RA), Merck / EMD (DH, EKH, RA, GI, FP, AL, MT, PG, MG, PD, CB, MT, MS, JLS, PS, DF, FG, KB, BVW, TC, DS, HB, TK), Mitsubishi (FGM), Ministero Italiano della Universit e della Ricerca Scientifica (FP), Mylan (FP, AL), Novartis (DH, EKH, RA, GI, FP, AL, MT, PG, FGM, MG, PD, CB, MT, MS, JLS, PS, DF, FG, JP, KB, BVW, TC, DS, HB, TK), ONO Pharmaceuticals (FGM), Roche (DH, EKH, RA, GI, FP, AL, MT, CB, FG, KB, BVW, TC, TK), Teva (DH, EKH, GI, FP, AL, MT, PG, FGM, MG, PD, CB, MT, JLS, PS, DF, JP, KB, BVW, TC, DS, TK), WebMD Global (TK). Authors of the French Multiple Sclerosis registry have received speaker honoraria, advisory board or steering committee fees, independent data monitoring committees fee, consultancy or lecturing fees, research support, unconditional PhD donation, and/or conference travel support from or served as principal investigators in clinical trials for Actelion (PC, ET), Ad Scientiam (EM), Akcea (JPC), Alnylam (JPC), Almirall (OH), Bayer (GE, HZ, OH), Biogen (GE, JC, AR, JDS, EM, HZ, PL, GD, TM, EB, PC, JP, BS, ET, OH, BB, OC, AMo, JPC, AMa, IP, NM, CL, DAL, SV, AW), Celgene (ET, DAL), CSL-Behring (JPC), FHU Imminent (HZ), Geneuro (SV), Genzyme-Sanofi (GE, JC, AR, JDS, EM, HZ, PL, GD, CLF, TM, EB, PC, JP, BS, ET, OH, BB, OC, AMo, JPC, AMa, IP, NM, CL, DAL, SV), Grifols (JPC), Laboratoire Français des Biotechnologies (JPC), LFB (GE), LFSEP (HZ), Merck / EMD (GE, JC, AR, EM, HZ, PL, GD, PC, JP, BS, ET, OH, BB, OC, AMo, JPC, AMa, NM, DAL, SV), Medday (EL, AR, TM, PC, JP, DAL, SV), Natus (JPC), Novartis (EL, GE, JC, AR, JDS, EM, HZ, PL, GD, CLF, TM, EB, PC, JP, BS, ET, OH, BB, OC, AMo, JPC, AMa, IP, NM, CL, DAL, SV), Pfizer (JPC), Pharmalliance (JPC), Roche (ML, EL, GE, JC, AR, JDS, EM, HZ, PL, GD, CLF, EB, PC, JP, BS, ET, OH, BB, OC, AMa, IP, NM, DAL, SV, AW), SNF-Floerger (JPC), Teva (GE, JC, AR, JDS, EM, HZ, PL, GD, EB, PC, JP, ET, OH, BB, AMo, JPC, AMa, SV), Académie de Médecine (HZ), Agence Nationale de la Recherche (DAL), French National Security Agency of Medicines and Health Products (EL), the EDMUS Foundation (EL), the ARSEP foundation (ML, GE, HZ, ET, DAL), PHRC Foundation (ET), Rennes University Hospital (GE). Authors of the Danish Multiple Sclerosis Registry have received speaker honoraria, advisory board or steering committee fees, independent data monitoring committees fee, consultancy fees, research support, and/or conference travel support from Almirall (JF), Bayer (HKM), Biogen (NKH, FS, CH, PVR, MBJ, JF, SB, HKM, KIS, MM), Celgene (PSS), Genzyme-Sanofi (FS, PSS, CH, PVR, MBJ, JF, SB, HKM, KIS, MM), GSK (PSS), Medday (PSS), Merck / EMD (JBA, NKH, FS, PSS, CH, PVR, MBJ, JF, SB, HKM, KIS, MM), Novartis (NKH, FS, PSS, CH, PVR, MBJ, JF, KIS, MM), Roche (FS, CH, PVR, MBJ, JF, SB, KIS, MM), Teva (NKH, FS, PSS, PVR, MBJ, JF, HKM, KIS, MM).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85115657202&partnerID=8YFLogxK
U2 - 10.1007/s40263-021-00860-7
DO - 10.1007/s40263-021-00860-7
M3 - Article
C2 - 34536228
AN - SCOPUS:85115657202
SN - 1172-7047
VL - 35
SP - 1217
EP - 1232
JO - CNS Drugs
JF - CNS Drugs
IS - 11
ER -
