TY - JOUR

T1 - The effectiveness of natalizumab vs fingolimod–A comparison of international registry studies

AU - Andersen, Johanna B.

AU - Sharmin, Sifat

AU - Lefort, Mathilde

AU - Koch-Henriksen, Nils

AU - Sellebjerg, Finn

AU - Sørensen, Per Soelberg

AU - Hilt Christensen, Claudia C.

AU - Rasmussen, Peter V.

AU - Jensen, Michael B.

AU - Frederiksen, Jette L.

AU - Bramow, Stephan

AU - Mathiesen, Henrik K.

AU - Schreiber, Karen I.

AU - Horakova, Dana

AU - Havrdova, Eva K.

AU - Alroughani, Raed

AU - Izquierdo, Guillermo

AU - Eichau, Sara

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 - Shaygannejad, Vahid

AU - Prevost, Julie

AU - Skibina, Olga

AU - Solaro, Claudio

AU - Karabudak, Rana

AU - Wijmeersch, Bart V.

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 - Sèze, Jérôme D.

AU - Maillart, Elisabeth

AU - Zephir, Hélène

AU - Labauge, Pierre

AU - Defer, Gilles

AU - Lebrun, 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, Abdullatif

AU - Bourre, Bertrand

AU - Casez, Olivier

AU - Cabre, Philippe

AU - Montcuquet, Alexis

AU - Wahab, Abir

AU - Camdessanché, Jean Philippe

AU - Marousset, Aude

AU - Patry, Ivania

AU - Hankiewicz, Karolina

AU - Pottier, Corinne

AU - Maubeuge, Nicolas

AU - Labeyrie, Céline

AU - Nifle, Chantal

AU - Leray, Emmanuelle

AU - Laplaud, David A.

AU - Butzkueven, Helmut

AU - Kalincik, Tomas

AU - Vukusic, Sandra

AU - Magyari, Melinda

N1 - Publisher Copyright: © 2021 Elsevier B.V.

PY - 2021

Y1 - 2021

N2 - Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

AB - Background: Natalizumab and fingolimod were the first preparations recommended for disease breakthrough in priorly treated relapsing-remitting multiple sclerosis. Of three published head-to-head studies two showed that natalizumab is the more effective to prevent relapses and EDSS worsening. Methods: By re-analyzing original published results from MSBase, France, and Denmark using uniform methodologies, we aimed at identifying the effects of differences in methodology, in the MS-populations, and at re-evaluating the differences in effectiveness between the two drugs. We gained access to copies of the individual amended databases and pooled all data. We used uniform inclusion/exclusion criteria and statistical methods with Inverse Probability Treatment Weighting. Results: The pooled analyses comprised 968 natalizumab- and 1479 fingolimod treated patients. The on-treatment natalizumab/fingolimod relapse rate ratio was 0.77 (p=0.004). The hazard ratio (HR) for a first relapse was 0.82 (p=0.030), and the HR for sustained EDSS improvement was 1.4 (p=0.009). There were modest differences between each of the original published studies and the replication study, but the conclusions of the three original studies remained unchanged: in two of them natalizumab was more effective, but in the third there was no difference between natalizumab and fingolimod. Conclusion: The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

KW - Fingolimod

KW - Head-to-head comparison

KW - Multiple sclerosis

KW - Natalizumab

KW - Treatment effectiveness

U2 - 10.1016/j.msard.2021.103012

DO - 10.1016/j.msard.2021.103012

M3 - Journal article

C2 - 34116480

AN - SCOPUS:85107568058

VL - 53

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

SN - 2211-0348

M1 - 103012

ER -