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
AU - Danish Multiple Sclerosis Registry
AU - OFSEP investigators
AU - Brochet, Bruno
AU - Cotton, Francois
AU - Douek, Pascal
AU - Olaiz, Javier
AU - Marignier, Romain
AU - Collongues, Nicolas
AU - Lubetzki, Catherine
AU - Vermersch, Patrick
AU - Cohen, Mikael
AU - Fromont, Agnes
AU - Wiertlewsky, Sandrine
AU - Audoin, Bertrand
AU - Giannesini, Claire
AU - Creange, Alain
AU - Faure, Justine
AU - MSBase Study Group
AU - Cabrera-Gomez, Jose Antonio
AU - Roullet, Etienne
AU - Zwanikken, Cees
AU - den Braber-Moerland, Leontien
AU - Gerlach , Oliver
AU - Deri, Norma
AU - Saladino, M
AU - Rojas, Juan Ignacio
AU - Vrech, Carlos
AU - Kermode, Allan
AU - Fabis-Pedrini, Marzena
AU - Barnett, Michael
AU - Shaw, Cameron P.
AU - Butler, Ernest
AU - Hodgkinson, Suzanne
AU - Boggild, Mike
AU - Taylor, Bruce
AU - Macdonell, Richard
AU - Hardy, Todd
AU - Pesch, Vincent Van
AU - Van Hijfte, Liesbeth
AU - Fragoso, Yara
AU - Moore, Fraser
AU - Kappos, Ludwig
AU - Ampapa, Radek
AU - Zakaria, Magd
AU - Fernandez Bolaños, Ricardo
AU - Olascoaga, Javier
AU - Perez Sempere, Angel
AU - Sanchez-Menoyo, Jose Luis
AU - Ramo-Tello, Cristina
AU - Andres Dominguez, Jose
AU - Aguera-Morales, Eduardo
AU - Hughes, Stella
AU - Gray, Orla
AU - Piroska, Imre
AU - Rozsa, Csilla
AU - Kasa, Krisztian
AU - Simo, Magdolna
AU - Kovacs, Krisztina
AU - Erdelyi, T.
AU - Sas, A.
AU - Dobos, Eniko
AU - Rajda, Cecilia
AU - McGuigan, Christopher
AU - Cartechini, E.
AU - Diamanti, Matteo
AU - Bergamaschi, Roberto
AU - Iuliano, Gerardo
AU - Solaro, Claudio
AU - Verheul, Freek
AU - Alkhaboori, Jabir
AU - Josa Sa , Maria
AU - Sirbu, Carmen-Adella
AU - Al-Harbi, Talal
AU - Sidhom, Youssef
AU - Gouider, Riadh
AU - Altintas, Ayse
AU - Soysal, Aysun
AU - Kister, Ilya
AU - Chisari, Clara
AU - D’Amico, Emanuele
AU - Fermo Salvatore, Lo
AU - Marriott, Mark P.
AU - Kilpatrick, Trevor
AU - King, John
AU - Nguyen, Ai Lan
AU - Dwyer, Chris
AU - Monif, Mastura
AU - Roos, Izanne
AU - Taylor, Lisa
AU - Baker, Josephine
AU - De Luca, Giovanna
AU - Di Tommaso, Valeria
AU - Travaglini, Daniela
AU - Pietrolongo, Erika
AU - di Ioia, Maria
AU - Farina, Deborah
AU - Mancinelli, Luca
AU - Larochelle, Catherine
AU - Vitetta, Francesca
AU - Simone, Anna Maria
AU - Curti, Erica
AU - Tsantes, Elena
AU - Sartori, Charlotte
AU - Quddus, Sabah
AU - Hinson, E.
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.
KW - natalizumab
KW - Fingolimod
KW - relapsing-remitting
KW - multiple sclerosis (MS)
KW - RRMS
KW - EDSS score
UR - http://www.scopus.com/inward/record.url?scp=85115657202&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1140766
UR - http://purl.org/au-research/grants/NHMRC/1129789
UR - http://purl.org/au-research/grants/NHMRC/1157717
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 -