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Journal Articles Neurology Year : 2022

Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis

Izanne Roos (1) , Charles Malpas , Emmanuelle Leray (2, 3, 4, 5, 6) , Romain Casey (7, 8) , Dana Horakova , Eva Kubala Havrdova , Marc Debouverie (9) , Francesco Patti , Jerome de Seze (10) , Guillermo Izquierdo , Sara Eichau , Gilles Edan (11, 5) , Alexandre Prat , Marc Girard , Serkan Ozakbas , Pierre Grammond , Helene Zephir , Jonathan Ciron , Elisabeth Maillart , Pamela Ann Mccombe , Thibault Moreau (12) , Maria Pia Amato , Pierre Labauge , Bertrand Bourre , Raed Alroughani , Katherine Buzzard , Olga Skibina , Murat Terzi , David Axel Laplaud (13, 14) , Eric Berger , Mark Slee , Francois Grand'Maison , Christine Lebrun-Frenay (15) , Elisabetta Cartechini , Aysun Soysal , Cavit Boz , Jeannette Lechner-Scott , Pierre Clavelou (16) , Bruno Stankoff (17) , Julie Prevost , Ludwig Kappos , Jean Pelletier (18) , Vahid Shaygannejad , Bassem Yamout , Samia Khoury , Oliver Gerlach , Daniele Spitaleri , Vincent van Pesch , Olivier Gout , Recai Turkoglu , Olivier Heinzlef , Eric Thouvenot (19) , Tamara Castillo-Trivino , Serge Bakchine , Radek Ampapa , Ernest Gerard Butler , Abir Wahab , Richard Macdonell , Eduardo Aguera-Morales , Philippe Cabre , Nasr Haifa Ben , Anneke van der Walt , Guy Laureys , Liesbeth van Hijfte , Cristina Ramo-Tello , Nicolas Maubeuge , Suzanne Hodgkinson , José Luis Sánchez-Menoyo , Michael Barnett , Celine Labeyrie , Steve Vucic , Youssef Sidhom , Riadh Gouider , Tunde Csepany , Javier Sotoca , Koen de Gans , Abdullah Al-Asmi , Yara Dadalti Fragoso , Sandra Vukusic (7, 8) , Helmut Butzkueven , Tomas Kalincik (1)
Izanne Roos
Charles Malpas
  • Function : Author
Dana Horakova
  • Function : Author
Eva Kubala Havrdova
  • Function : Author
Francesco Patti
  • Function : Author
Jerome de Seze
  • Function : Author
Guillermo Izquierdo
  • Function : Author
Sara Eichau
  • Function : Author
Alexandre Prat
  • Function : Author
Marc Girard
  • Function : Author
Serkan Ozakbas
  • Function : Author
Pierre Grammond
  • Function : Author
Helene Zephir
  • Function : Author
Jonathan Ciron
Elisabeth Maillart
Pamela Ann Mccombe
  • Function : Author
Maria Pia Amato
  • Function : Author
Pierre Labauge
  • Function : Author
Bertrand Bourre
Raed Alroughani
  • Function : Author
Katherine Buzzard
  • Function : Author
Olga Skibina
  • Function : Author
Murat Terzi
  • Function : Author
Eric Berger
  • Function : Author
Mark Slee
  • Function : Author
Francois Grand'Maison
Elisabetta Cartechini
  • Function : Author
Aysun Soysal
  • Function : Author
Cavit Boz
  • Function : Author
Jeannette Lechner-Scott
  • Function : Author
Pierre Clavelou
  • Function : Author
Bruno Stankoff
Julie Prevost
  • Function : Author
Ludwig Kappos
  • Function : Author
Vahid Shaygannejad
  • Function : Author
Bassem Yamout
  • Function : Author
Samia Khoury
  • Function : Author
Oliver Gerlach
  • Function : Author
Daniele Spitaleri
  • Function : Author
Vincent van Pesch
Olivier Gout
  • Function : Author
Recai Turkoglu
Olivier Heinzlef
  • Function : Author
Eric Thouvenot
Tamara Castillo-Trivino
Serge Bakchine
  • Function : Author
Radek Ampapa
  • Function : Author
Ernest Gerard Butler
  • Function : Author
Abir Wahab
  • Function : Author
Richard Macdonell
  • Function : Author
Eduardo Aguera-Morales
Philippe Cabre
  • Function : Author
Nasr Haifa Ben
  • Function : Author
Anneke van der Walt
Guy Laureys
Liesbeth van Hijfte
  • Function : Author
Cristina Ramo-Tello
  • Function : Author
Nicolas Maubeuge
  • Function : Author
Suzanne Hodgkinson
  • Function : Author
José Luis Sánchez-Menoyo
Michael Barnett
Celine Labeyrie
  • Function : Author
Steve Vucic
  • Function : Author
Youssef Sidhom
  • Function : Author
Riadh Gouider
  • Function : Author
Tunde Csepany
Javier Sotoca
  • Function : Author
Koen de Gans
  • Function : Author
Abdullah Al-Asmi
Yara Dadalti Fragoso
Helmut Butzkueven
  • Function : Author
Tomas Kalincik
  • Function : Correspondent author
  • PersonId : 1098429

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Abstract

Background and objectives - To evaluate the rate of return of disease activity after cessation of multiple sclerosis (MS) disease-modifying therapy. Methods - This was a retrospective cohort study from 2 large observational MS registries: MSBase and OFSEP. Patients with relapsing-remitting MS who had ceased a disease-modifying therapy and were followed up for the subsequent 12 months were included in the analysis. The primary study outcome was annualized relapse rate in the 12 months after disease-modifying therapy discontinuation stratified by patients who did, and did not, commence a subsequent therapy. The secondary endpoint was the predictors of first relapse and disability accumulation after treatment discontinuation. Results - A total of 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for 7 therapies. Annualized rates of relapse (ARRs) started to increase 2 months after natalizumab cessation (month 2-4 ARR 0.47, 95% CI 0.43-0.51). Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation (mean ARR difference: 0.15, 0.08-0.22). After discontinuation of fingolimod, rates of relapse increased overall (month 1-2 ARR: 0.80, 0.70-0.89) and stabilized faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01 to 0.29). The magnitude of disease reactivation for other therapies was low but reduced further by commencement of another treatment 1-10 months after treatment discontinuation. Predictors of relapse were a higher relapse rate in the year before cessation, female sex, younger age, and higher EDSS score. Commencement of a subsequent therapy reduced both the risk of relapse (HR 0.76, 95% CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). Discussion - The rate of disease reactivation after treatment cessation differs among MS treatments, with the peaks of relapse activity ranging from 1 to 10 months in untreated cohorts that discontinued different therapies. These results suggest that untreated intervals should be minimized after stopping antitrafficking therapies (natalizumab and fingolimod). Classification of evidence - This study provides Class III that disease reactivation occurs within months of discontinuation of MS disease-modifying therapies. The risk of disease activity is reduced by commencement of a subsequent therapy.

Dates and versions

hal-03776286 , version 1 (13-09-2022)

Identifiers

Cite

Izanne Roos, Charles Malpas, Emmanuelle Leray, Romain Casey, Dana Horakova, et al.. Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis. Neurology, 2022, 99 (17), pp.e1926-e1944. ⟨10.1212/WNL.0000000000201029⟩. ⟨hal-03776286⟩
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