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 - Sellebjerg, Finn Thorup

AU - Soerensen, Per Soelberg

AU - Jensen, Michael Broksgaard

AU - Frederiksen, Jette Lautrup

AU - Bramow, Stephan

AU - Mathiesen, Henrik Kahr

AU - Schreiber, Karen Ingrid

AU - Magyari, Melinda

AU - Danish Multiple Sclerosis Registry, OFSEP and the MSBase investigators

N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.

PY - 2021

Y1 - 2021

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.

U2 - 10.1007/s40263-021-00860-7

DO - 10.1007/s40263-021-00860-7

M3 - Journal article

C2 - 34536228

AN - SCOPUS:85115657202

VL - 35

SP - 1217

EP - 1232

JO - CNS Drugs

JF - CNS Drugs

SN - 1172-7047

ER -