Determinants of therapeutic lag in multiple sclerosis.


Journal

Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185

Informations de publication

Date de publication:
10 2021
Historique:
pubmed: 12 1 2021
medline: 26 10 2021
entrez: 11 1 2021
Statut: ppublish

Résumé

A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups. The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation. Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants. High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5). Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Sections du résumé

BACKGROUND
A delayed onset of treatment effect, termed therapeutic lag, may influence the assessment of treatment response in some patient subgroups.
OBJECTIVES
The objective of this study is to explore the associations of patient and disease characteristics with therapeutic lag on relapses and disability accumulation.
METHODS
Data from MSBase, a multinational multiple sclerosis (MS) registry, and OFSEP, the French MS registry, were used. Patients diagnosed with MS, minimum 1 year of exposure to MS treatment and 3 years of pre-treatment follow-up, were included in the analysis. Studied outcomes were incidence of relapses and disability accumulation. Therapeutic lag was calculated using an objective, validated method in subgroups stratified by patient and disease characteristics. Therapeutic lag under specific circumstances was then estimated in subgroups defined by combinations of clinical and demographic determinants.
RESULTS
High baseline disability scores, annualised relapse rate (ARR) ⩾ 1 and male sex were associated with longer therapeutic lag on disability progression in sufficiently populated groups: females with expanded disability status scale (EDSS) < 6 and ARR < 1 had mean lag of 26.6 weeks (95% CI = 18.2-34.9), males with EDSS < 6 and ARR < 1 31.0 weeks (95% CI = 25.3-36.8), females with EDSS < 6 and ARR ⩾ 1 44.8 weeks (95% CI = 24.5-65.1), and females with EDSS ⩾ 6 and ARR < 1 54.3 weeks (95% CI = 47.2-61.5).
CONCLUSIONS
Pre-treatment EDSS and ARR are the most important determinants of therapeutic lag.

Identifiants

pubmed: 33423618
doi: 10.1177/1352458520981300
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1838-1851

Auteurs

Izanne Roos (I)

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

Emmanuelle Leray (E)

Rennes University, EHESP, REPERES - EA 7449, Rennes, France/Rennes University, CHU Rennes, Inserm, CIC 1414 [(Centre d'Investigation Clinique de Rennes)], Rennes, France.

Federico Frascoli (F)

Faculty of Science, Engineering and Technology, School of Science, Department of Mathematics, Swinburne University of Technology, Melbourne, VIC, Australia.

Romain Casey (R)

Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France/Hospices Civils de Lyon, Service de Neurologie, sclérose en plaques, pathologies de la myéline et neuro-inflammation, Bron, France/Observatoire Français de la Sclérose en Plaques, Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292, Lyon, France/EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, State-Approved Foundation, Bron, France.

J William L Brown (JWL)

CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, Australia/Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

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 Kubala 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.

Marc Debouverie (M)

Department of Neurology, Nancy University Hospital, Nancy, France/Université de Lorraine, APEMAC, Nancy, France.

Maria Trojano (M)

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

Francesco Patti (F)

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

Guillermo Izquierdo (G)

Hospital Universitario Virgen Macarena, Sevilla, Spain.

Sara Eichau (S)

Hospital Universitario Virgen Macarena, Sevilla, Spain.

Gilles Edan (G)

Centre hospitalier universitaire de Rennes, Hôpital Pontchaillou, Service de neurologie, CIC1414 INSERM, Rennes, France.

Alexandre Prat (A)

CHUM MS Center and Universite de Montreal, Montreal, QC, Canada.

Marc Girard (M)

CHUM MS Center and Universite de Montreal, Montreal, QC, Canada.

Pierre Duquette (P)

CHUM MS Center and Universite de Montreal, Montreal, QC, Canada.

Marco Onofrj (M)

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

Alessandra Lugaresi (A)

IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italia/Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italia.

Pierre Grammond (P)

CISSS Chaudière-Appalache, Lévis, QC, Canada.

Jonathan Ciron (J)

Hôpital Pierre-Paul Riquet, Department of Neurology, CHU de Toulouse, CRC-SEP, Toulouse, France.

Aurélie Ruet (A)

University Bordeaux, Bordeaux, France/INSERM U1215, Neurocentre Magendie, Bordeaux, France/Department of Neurology, CHU de Bordeaux, CIC Bordeaux CIC1401, Bordeaux, France.

Serkan Ozakbas (S)

Dokuz Eylul University, Konak/Izmir, Turkey.

Jérôme De Seze (J)

CHU de Strasbourg, Department of Neurology and Clinical Investigation Center, CIC (centre d'investigation clinique) INSERM 1434, Strasbourg, France.

Céline Louapre (C)

Sorbonne Université, Institut du Cerveau, ICM, Assistance Publique Hôpitaux de Paris APHP, Département de neurologie, Hôpital de la Pitié Salpêtrière, Paris, France.

Hélène Zephir (H)

CHU Lille, CRCSEP Lille, Univ Lille, U1172, Lille, France.

Maria José Sá (MJ)

Centro Hospitalar Universitário de São João and Universidade Fernando Pessoa, Porto, Portugal.

Patrizia Sola (P)

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

Diana Ferraro (D)

Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.

Pierre Labauge (P)

CHU de Montpellier, MS Unit, Montpellier, France/University of Montpellier (MUSE), Montpellier, France.

Gilles Defer (G)

CHU de Caen, MS Expert Centre, Department of Neurology, avenue de la Côte-de-Nacre, Normandy University, Caen, France.

Roberto Bergamaschi (R)

IRCCS Mondino Foundation, Pavia, Italy.

Christine Lebrun-Frenay (C)

CRCSEP Nice, UR2CA, Université Nice Cote d'Azur, Centre hospitalier universitaire de Nice, Hopital Pasteur 2, Nice, France.

Cavit Boz (C)

KTU Medical Faculty Farabi Hospital, Trabzon, Turkey.

Elisabetta Cartechini (E)

UOC Neurologia, Azienda Sanitaria Unica Regionale Marche - AV3, Macerata, Italy.

Thibault Moreau (T)

CHU de Dijon, Department of Neurology, EA4184, Dijon, France.

David Laplaud (D)

CHU de Nantes, Service de Neurologie & CIC015 INSERM, Nantes, France/CRTI-Inserm U1064, Nantes, France.

Jeannette Lechner-Scott (J)

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

Francois Grand'Maison (F)

Neuro Rive-Sud, Quebec, QC, Canada.

Oliver Gerlach (O)

Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.

Murat Terzi (M)

Medical Faculty, 19 Mayis University, Samsun, Turkey.

Franco Granella (F)

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

Raed Alroughani (R)

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

Gerardo Iuliano (G)

Ospedali Riuniti di Salerno, Salerno, Italy.

Vincent Van Pesch (V)

Cliniques universitaires Saint-Luc, UCLouvain, Bruxelles, Belgium.

Bart Van Wijmeersch (B)

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

Daniele LA Spitaleri (D)

Neurological Unit AORN San G. Moscati, Avellino, Italy.

Aysun Soysal (A)

Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.

Eric Berger (E)

CHU de Besançon, Department of Neurology, Besançon, France.

Julie Prevost (J)

CSSS Saint-Jérôme, Saint-Jerome, QC, Canada.

Eduardo Aguera-Morales (E)

Hospital Universitario Reina Sofia Cordoba (IMIBIC), Cordoba, Spain.

Pamela McCombe (P)

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

Tamara Castillo Triviño (T)

Instituto de Investigación Sanitaria Biodonostia, Hospital Universitario Donostia, San Sebastian, Spain.

Pierre Clavelou (P)

CHU Clermont-Ferrand, Department of Neurology, Clermont-Ferrand, France/Université Clermont Auvergne, Inserm, Neuro-Dol, Clermont-Ferrand, France.

Jean Pelletier (J)

Aix Marseille Univ, APHM, Hôpital de la Timone, Pôle de Neurosciences Cliniques, Service de Neurologie, Marseille, France.

Recai Turkoglu (R)

Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.

Bruno Stankoff (B)

Sorbonne Universités, UPMC Paris 06, Brain and Spine Institute, ICM, Hôpital de la Pitié Salpêtrière, Inserm UMR S 1127, CNRS UMR 7225, Pars, France/Department of Neurology, AP-HP, Saint-Antoine Hospital, Paris, France.

Olivier Gout (O)

Fondation Adolphe de Rothschild de l'œil et du cerveau, Department of Neurology, Paris, France.

Eric Thouvenot (E)

CHU de Nîmes, Department of Neurology, Nîmes, France/Institut de Génomique Fonctionnelle, UMR5203, INSERM 1191, Université de Montpellier, Montpellier, France.

Olivier Heinzlef (O)

Centre hospitalier intercommunal de Poissy Saint-Germain-en-Laye, Departement of Neurology, Poissy, France.

Youssef Sidhom (Y)

Department of Neurology - LR 18 SP03 - CIC Neurosciences, Razi Hospital, La Manouba, Tunisia.

Riadh Gouider (R)

Department of Neurology - LR 18 SP03 - CIC Neurosciences, Razi Hospital, La Manouba, Tunisia/Faculty of Medicine, UTM, Tunis, Tunisia.

Tunde Csepany (T)

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

Bertrand Bourre (B)

Centre hospitalier universitaire Rouen Normandie, Hôpital Charles-Nicolle, Departement of Neurology, Rouen, France.

Abdullatif Al Khedr (A)

Amiens University Hospital, Department of Neurology, place Victor Pauchet, Amiens, France.

Olivier Casez (O)

Department of Neurology, Centre hospitalier universitaire Grenoble-Alpes, La Tronche/Grenoble, France.

Philippe Cabre (P)

Centre hospitalier universitaire de Martinique, Department of Neurology, Hôpital Pierre Zobda-Quitman, Fort-de-France, France.

Alexis Montcuquet (A)

Centre hospitalier universitaire Limoges, Department of Neurology, Hôpital Dupuytren, Limoges, France.

Abir Wahab (A)

Assistance publique des hôpitaux de Paris, Department of Neurology, Hôpital Henri Mondor, Créteil, France.

Jean-Philippe Camdessanche (JP)

Centre hospitalier universitaire de Saint-Étienne, Department of Neurology, Hôpital Nord, Saint-Étienne, France.

Aude Maurousset (A)

Centre hospitalier régional universitaire de Tours, Department of Neurology, Hôpital Bretonneau, CRCSEP, Tours, France.

Ivania Patry (I)

Department of Neurology, Centre Hospitalier Sud Francilien, Corbeil Essonnes, France.

Karolina Hankiewicz (K)

Department of Neurology, Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, Saint-Denis, France.

Corinne Pottier (C)

Department of Neurology, Centre hospitalier de Pontoise, Hôpital René Dubos, Pontoise, France.

Nicolas Maubeuge (N)

CHU La Milétrie, Hôpital Jean Bernard, Department of Neurology, Poitiers, France.

Céline Labeyrie (C)

Assistance publique des hôpitaux de Paris, Hôpital Bicêtre, Department of Neurology, Le Kremlin Bicêtre, France.

Chantal Nifle (C)

Hopital Andre Mignot, Department of Neurology, 177 Rue de Versailles, Le Chesnay, France.

Alasdair Coles (A)

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Charles B Malpas (CB)

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

Sandra Vukusic (S)

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

Helmut Butzkueven (H)

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

Tomas Kalincik (T)

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

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