Natalizumab Versus Fingolimod in Patients with Relapsing-Remitting Multiple Sclerosis: A Subgroup Analysis From Three International Cohorts
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | CNS Drugs |
| Vol/bind | 35 |
| Sider (fra-til) | 1217–1232 |
| ISSN | 1172-7047 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
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.
ID: 281162239