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


Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Aug 2021
Historique:
received: 31 01 2021
revised: 21 04 2021
accepted: 29 04 2021
pubmed: 12 6 2021
medline: 25 8 2021
entrez: 11 6 2021
Statut: ppublish

Résumé

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. 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. 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. The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Sections du résumé

BACKGROUND 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 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 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 CONCLUSIONS
The results were largely invariant to the epidemiological and statistical methods but differed between the MS populations. Generally, the advantage of natalizumab was confirmed.

Identifiants

pubmed: 34116480
pii: S2211-0348(21)00279-0
doi: 10.1016/j.msard.2021.103012
pii:
doi:

Substances chimiques

Immunosuppressive Agents 0
Natalizumab 0
Fingolimod Hydrochloride G926EC510T

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103012

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Auteurs

Johanna B Andersen (JB)

The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. Electronic address: johanna.balslev.andersen@regionh.dk.

Sifat Sharmin (S)

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.

Mathilde Lefort (M)

Rennes University, EHESP, REPERES - EA 7449, F-35000 Rennes, France; Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), F-35000 Rennes, France.

Nils Koch-Henriksen (N)

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

Finn Sellebjerg (F)

The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark.

Per Soelberg Sørensen (PS)

The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Claudia C Hilt Christensen (CC)

Department of Neurology Aalborg University Hospital, Multiple Sclerosis Unit.

Peter V Rasmussen (PV)

Aarhus University Hospital, Neurology, PPJ Boulevard, DK-8200 Aarhus N.

Michael B Jensen (MB)

Department of Neurology, University Hospital of Northern Sealand.

Jette L Frederiksen (JL)

Danish Multiple Sclerosis Centre, Dept. of Neurology, Copenhagen University Hospital, Rigshospitalet in Glostrup, 2600 Glostrup, Denmark.

Stephan Bramow (S)

The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark.

Henrik K Mathiesen (HK)

The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Karen I Schreiber (KI)

The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark.

Dana Horakova (D)

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.

Eva K Havrdova (EK)

Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.

Raed Alroughani (R)

Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.

Guillermo Izquierdo (G)

Hospital Universitario Virgen Macarena, Sevilla, Spain.

Sara Eichau (S)

Hospital Universitario Virgen Macarena, Sevilla, Spain.

Serkan Ozakbas (S)

Dokuz Eylul University, Konak/Izmir, Turkey.

Francesco Patti (F)

GF Ingrassia Department, University of Catania, Catania, Policlinico G Rodolico, Italy.

Marco Onofrj (M)

Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chieti, Italy.

Alessandra Lugaresi (A)

Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.

Murat Terzi (M)

Medical Faculty, 19 Mayis University, Samsun, Turkey.

Pierre Grammond (P)

CISSS Chaudiere-Appalache, Levis, Canada.

Francois Grand Maison (F)

Neuro Rive-Sud, Quebec, Canada.

Bassem Yamout (B)

Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.

Alexandre Prat (A)

Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada.

Marc Girard (M)

Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada.

Pierre Duquette (P)

Hopital Notre Dame, Montreal, Canada, CHUM and Universite de Montreal, Montreal, Canada.

Cavit Boz (C)

KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.

Maria Trojano (M)

Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.

Pamela McCombe (P)

University of Queensland, Brisbane, Australia, Royal Brisbane and Women's Hospital.

Mark Slee (M)

Flinders University, Adelaide, Australia.

Jeannette Lechner-Scott (J)

School of Medicine and Public Health, University Newcastle, Newcastle, Australia; Department of Neurology, John Hunter Hospital, Hunter New England Health, Newcastle, Australia.

Recai Turkoglu (R)

Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.

Patrizia Sola (P)

Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.

Diana Ferraro (D)

Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy.

Franco Granella (F)

Department of Medicine and Surgery, University of Parma, Parma, Italy; Department of Emergency and General Medicine, Parma University Hospital, Parma, Italy.

Vahid Shaygannejad (V)

Isfahan University of Medical Sciences, Isfahan, Iran.

Julie Prevost (J)

CSSS Saint-Jerome, Saint-Jerome, Canada.

Olga Skibina (O)

Monash University, Melbourne, Australia.

Claudio Solaro (C)

Department of Neurology, ASL3 Genovese, Genova, Italy; Department of Rehabilitaiton, ML Novarese Hospital Moncrivello.

Rana Karabudak (R)

Hacettepe University, Ankara, Turkey.

Bart V Wijmeersch (BV)

Rehabilitation and MS-Centre Overpelt and Hasselt University, Hasselt, Belgium.

Tunde Csepany (T)

Department of Neurology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Daniele Spitaleri (D)

Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.

Steve Vucic (S)

Westmead Hospital, Sydney, Australia.

Romain Casey (R)

Service de neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, 69677 Lyon/Bron, France; Centre des Neurosciences de Lyon, Observatoire Français de la Sclérose en Plaques, INSERM 1028 et CNRS UMR5292, 69003 Lyon, France ; Université Claude Bernard Lyon 1, Faculté de médecine Lyon Est, F-69000 Lyon, France, Eugene Devic EDMUS Foundation, 69677 Lyon/Bron, France.

Marc Debouverie (M)

Centre hospitalier régional universitaire de Nancy, Hôpital central, Service de neurologie, Nancy, France.

Gilles Edan (G)

Centre hospitalier universitaire de Rennes, Hôpital Pontchaillou, Service de neurologie, Rennes, France.

Jonathan Ciron (J)

Centre hospitalier universitaire de Toulouse, Hôpital Purpan, Service de neurologie inflammatoire et neuro-oncologie, Toulouse, France.

Aurélie Ruet (A)

Centre hospitalier universitaire de Bordeaux, Hôpital Pellegrin, Service de neurologie, Bordeaux, France.

Jérôme D Sèze (JD)

Hôpitaux universitaire de Strasbourg, Hôpital de Hautepierre, Service des maladies inflammatoires du système nerveux - neurologie, Strasbourg, France.

Elisabeth Maillart (E)

Assistance publique des hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Service de neurologie, Paris, France.

Hélène Zephir (H)

Centre hospitalier universitaire de Lille, Hôpital Salengro, Service de neurologie D, Lille, France.

Pierre Labauge (P)

Centre hospitalier universitaire de Montpellier, Hôpital Gui de Chauliac, Service de neurologie, Montpellier, France.

Gilles Defer (G)

Centre hospitalier universitaire de Caen Normandie, Service de neurologie, Hôpital Côte de Nacre, Caen, France.

Christine Lebrun (C)

Centre hospitalier universitaire de Nice, Université Nice Côte d'Azur, Hôpital Pasteur, Service de neurologie, Nice, France.

Thibault Moreau (T)

Centre hospitalier universitaire Dijon Bourgogne, Hôpital François Mitterrand, Service de neurologie, maladies inflammatoires du système nerveux et neurologie générale, Dijon, France.

Eric Berger (E)

Centre hospitalier régional universitaire de Besançon, Hôpital Jean Minjoz, Service de neurologie, Besançon, France.

Pierre Clavelou (P)

Centre hospitalier universitaire de Clermont-Ferrand, Hôpital Gabriel-Montpied, Service de neurologie, Clermont-Ferrand, France.

Jean Pelletier (J)

Assistance publique des hôpitaux de Marseille, Centre hospitalier de la Timone, Service de neurologie et unité neuro-vasculaire, Marseille, France.

Bruno Stankoff (B)

Assistance publique des hôpitaux de Paris, Hôpital Saint-Antoine, Service de neurologie, Paris, France.

Olivier Gout (O)

Fondation Adolphe de Rothschild de l'œil et du cerveau, Service de neurologie, Paris, France.

Eric Thouvenot (E)

Centre hospitalier universitaire de Nîmes, Hôpital Carémeau, Service de neurologie, Nîmes, France.

Olivier Heinzlef (O)

Centre hospitalier intercommunal de Poissy Saint-Germain-en-Laye, Service de neurologie, Poissy, France.

Abdullatif Al-Khedr (A)

Centre hospitalier universitaire d'Amiens Picardie, Site sud, Service de neurologie, Amiens, France.

Bertrand Bourre (B)

Centre hospitalier universitaire Rouen Normandie, Hôpital Charles-Nicolle, Service de neurologie, Rouen, France.

Olivier Casez (O)

Centre hospitalier universitaire Grenoble-Alpes, Site nord, Service de neurologie, Grenoble/La Tronche, France.

Philippe Cabre (P)

Centre hospitalier universitaire de Martinique, Hôpital Pierre Zobda-Quitman, Service de Neurologie, Fort-de-France, France.

Alexis Montcuquet (A)

Centre hospitalier universitaire Limoges, Hôpital Dupuytren, Service de neurologie, Limoges, France.

Abir Wahab (A)

Hôpital Henri Mondor, Department of Neurology, F-94000 Créteil, France.

Jean-Philippe Camdessanché (JP)

Centre hospitalier universitaire de Saint-Étienne, Hôpital Nord, Service de neurologie, Saint-Étienne, France.

Aude Marousset (A)

Centre hospitalier régional universitaire de Tours, Hôpital Bretonneau, Service de neurologie, Tours, France.

Ivania Patry (I)

Centre hospitalier sud francilien, Service de neurologie, Corbeil-Essonnes, France.

Karolina Hankiewicz (K)

Centre hospitalier de Saint-Denis, Hôpital Casanova, Service de neurologie, Saint-Denis, France.

Corinne Pottier (C)

Centre hospitalier de Pontoise, Service de neurologie, Pontoise, France.

Nicolas Maubeuge (N)

Centre hospitalier universitaire de Poitiers, Site de la Milétrie, Service de neurologie, Poitiers, France.

Céline Labeyrie (C)

Assistance publique des hôpitaux de Paris, Hôpital Bicêtre, Service de neurologie, Le Kremlin-Bicêtre, France.

Chantal Nifle (C)

Centre hospitalier de Versailles, Hôpital André-Mignot, Service de neurologie, Le Chesnay, France.

Emmanuelle Leray (E)

Rennes University, EHESP, REPERES - EA 7449, F-35000 Rennes, France; Univ Rennes, CHU Rennes, Inserm, CIC 1414 (Centre d'Investigation Clinique de Rennes), F-35000 Rennes, France.

David A Laplaud (DA)

CHU de Nantes, Service de Neurologie & CIC015 INSERM, F-44093 Nantes, France; INSERM CR1064, F-44000 Nantes, France.

Helmut Butzkueven (H)

Central Clinical School, Monash University, Melbourne, Australia; Department of Neurology, The Alfred Hospital, Melbourne, Australia; Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Australia.

Tomas Kalincik (T)

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Melbourne MS Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.

Sandra Vukusic (S)

The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; The Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Melinda Magyari (M)

The Danish Multiple Sclerosis Registry, Department of Neurology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; The Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet Glostrup, Denmark.

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