Variability of the response to immunotherapy among subgroups of patients with multiple sclerosis.


Journal

European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311

Informations de publication

Date de publication:
04 2023
Historique:
revised: 16 01 2023
received: 01 07 2022
accepted: 18 01 2023
pubmed: 25 1 2023
medline: 8 3 2023
entrez: 24 1 2023
Statut: ppublish

Résumé

This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Sections du résumé

BACKGROUND AND PURPOSE
This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS).
METHODS
We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics.
RESULTS
Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity.
CONCLUSIONS
DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Identifiants

pubmed: 36692895
doi: 10.1111/ene.15706
doi:

Banques de données

ANZCTR
['ACTRN12605000455662']

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1014-1024

Informations de copyright

© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

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Auteurs

Ibrahima Diouf (I)

Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.

Charles B Malpas (CB)

Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.
Department of Neurology, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Sifat Sharmin (S)

Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.

Izanne Roos (I)

Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.
Department of Neurology, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

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.

Francesco Patti (F)

Department of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.

Vahid Shaygannejad (V)

Isfahan University of Medical Sciences, Isfahan, Iran.

Serkan Ozakbas (S)

Dokuz Eylul University, Konak/Izmir, Turkey.

Guillermo Izquierdo (G)

Hospital Universitario Virgen Macarena, Seville, Spain.

Sara Eichau (S)

Hospital Universitario Virgen Macarena, Seville, Spain.

Marco Onofrj (M)

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

Alessandra Lugaresi (A)

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

Raed Alroughani (R)

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

Alexandre Prat (A)

CHUM Mississippi Center and University of Montreal, Montreal, Quebec, Canada.

Marc Girard (M)

CHUM Mississippi Center and University of Montreal, Montreal, Quebec, Canada.

Pierre Duquette (P)

CHUM Mississippi Center and University of Montreal, Montreal, Quebec, Canada.

Murat Terzi (M)

School of Medicine, Ondokuz Mayis University, Samsun, Turkey.

Cavit Boz (C)

KTU Medical Faculty, Farabi Hospital, Trabzon, Turkey.

Francois Grand'Maison (F)

Neuro Rive-Sud, Quebec City, Quebec, Canada.

Sherif Hamdy (S)

Neurology, Kasr Al Ainy MS Research Unit, Cairo, Egypt.

Patrizia Sola (P)

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

Diana Ferraro (D)

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

Pierre Grammond (P)

CISSS Chaudière-Appalache, Levis, Sainte-Marie, Quebec, Canada.

Recai Turkoglu (R)

Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.

Katherine Buzzard (K)

Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Olga Skibina (O)

Central Clinical School, Monash University, Melbourne, Victoria, Australia.

Bassem Yamout (B)

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

Ayse Altintas (A)

Department of Neurology, School of Medicine, Koc University, Istanbul, Turkey.
Koc University Research Center for Translational Medicine, Istanbul, Turkey.

Oliver Gerlach (O)

Zuyderland Medical Center, Sittard-Geleen, the Netherlands.

Vincent van Pesch (V)

Cliniques Universitaires Saint-Luc, Louvain, Brussels, Belgium.

Yolanda Blanco (Y)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic of Barcelona, Barcelona, Spain.

Davide Maimone (D)

Garibaldi Hospital, Catania, Italy.

Jeannette Lechner-Scott (J)

School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

Roberto Bergamaschi (R)

IRCCS Mondino Foundation, Pavia, Italy.

Rana Karabudak (R)

Hacettepe University, Ankara, Turkey.

Gerardo Iuliano (G)

Ospedali Riuniti di Salerno, Salerno, Italy.

Chris McGuigan (C)

St Vincent's University Hospital, Dublin, Ireland.

Elisabetta Cartechini (E)

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

Michael Barnett (M)

Brain and Mind Centre, Sydney, New South Wales, Australia.

Stella Hughes (S)

Royal Victoria Hospital, Belfast, UK.

Maria José Sa (MJ)

Department of Neurology, Centro Hospitalar Universitário de São João, Porto, Portugal.

Claudio Solaro (C)

Department of Neurology, ASL3 Genovese, Genoa, Italy.
Department of Rehabilitation, ML Novarese Hospital Moncrivello, Genoa, Italy.

Ludwig Kappos (L)

Departments of Medicine and Clinical Research, Neurologic Clinic and Policlinic, University Hospital and University of Basel, Basel, Switzerland.

Cristina Ramo-Tello (C)

Trias and Pujol Brothers University Hospital, Badalona, Spain.

Edgardo Cristiano (E)

Hospital Italiano, Buenos Aires, Argentina.

Suzanne Hodgkinson (S)

Liverpool Hospital, Sydney, New South Wales, Australia.

Daniele Spitaleri (D)

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

Aysun Soysal (A)

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

Thor Petersen (T)

Aarhus University Hospital, Aarhus, Denmark.

Mark Slee (M)

Flinders University, Adelaide, South Australia, Australia.

Ernest Butler (E)

Monash Medical Centre, Melbourne, Victoria, Australia.

Franco Granella (F)

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Koen de Gans (K)

Groene Hart Ziekenhuis, Gouda, the Netherlands.

Pamela McCombe (P)

University of Queensland, Brisbane, Queensland, Australia.

Radek Ampapa (R)

Nemocnice Jihlava, Jihlava, Czech Republic.

Bart Van Wijmeersch (B)

Rehabilitation and MS Center Overpelt and Hasselt University, Hasselt, Belgium.

Anneke van der Walt (A)

Central Clinical School, Monash University, Melbourne, Victoria, Australia.
Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.

Helmut Butzkueven (H)

Austin Health, Melbourne, Victoria, Australia.

Julie Prevost (J)

CSSS Saint-Jerome, Saint-Jerome, Quebec, Canada.

L G F Sinnige (LGF)

Medical Center Leeuwarden, Leeuwarden, the Netherlands.

Jose Luis Sanchez-Menoyo (JL)

Hospital de Galdakao-Usansolo, Galdakao, Spain.

Steve Vucic (S)

Westmead Hospital, Sydney, New South Wales, Australia.

Guy Laureys (G)

University Hospital Ghent, Ghent, Belgium.

Liesbeth Van Hijfte (L)

University Hospital Ghent, Ghent, Belgium.

Dheeraj Khurana (D)

Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Richard Macdonell (R)

Austin Health, Melbourne, Victoria, Australia.

Riadh Gouider (R)

Department of Neurology, Razi Hospital, Manouba, Tunisia.

Tamara Castillo-Triviño (T)

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

Orla Gray (O)

South East Trust, Belfast, UK.

Eduardo Aguera-Morales (E)

University Hospital Reina Sofia, Cordoba, Spain.

Abdullah Al-Asmi (A)

Department of Medicine, Sultan Qaboos University Hospital, Seeb, Oman.

Cameron Shaw (C)

University Hospital Geelong, Geelong, Victoria, Australia.

Norma Deri (N)

Hospital Fernandez, Buenos Aires, Argentina.

Talal Al-Harbi (T)

Neurology Department, King Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia.

Yara Fragoso (Y)

Universidade Metropolitana de Santos, Santos, Brazil.

Tunde Csepany (T)

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

Angel Perez Sempere (A)

Hospital General Universitario de Alicante, Alicante, Spain.

Irene Trevino-Frenk (I)

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

Jan Schepel (J)

Waikato Hospital, Hamilton, New Zealand.

Fraser Moore (F)

Jewish General Hospital, Montreal, Quebec, Canada.

Tomas Kalincik (T)

Department of Medicine, CORe, University of Melbourne, Melbourne, Victoria, Australia.
Department of Neurology, Neuroimmunology Centre, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

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