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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, * 
Abstract : 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 two 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 annualised 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: 14,213 patients, with 18,029 eligible treatment discontinuation epochs, were identified for seven therapies. Annualised rates of relapse (ARR) started to increase 2-months after natalizumab cessation (month 2-4 ARR, 95% confidence interval): 0.47, 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 stabilised faster in patients who started a new therapy within 1-2 months (mean ARR difference: 0.14, -0.01-0.29). 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 higher relapse rate in the year before cessation, female sex, younger age and higher EDSS. 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). Conclusion: 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 minimised after stopping anti-trafficking therapies (natalizumab and fingolimod). Classification of evidence: This study provides class III that disease reactivation occurs within months of discontinuation of multiple sclerosis disease-modifying therapies. Risk of disease activity is reduced by commencement of a subsequent therapy.
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Tuesday, September 13, 2022 - 3:35:23 PM
Last modification on : Wednesday, October 12, 2022 - 3:59:22 AM



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, pp.10.1212/WNL.0000000000201029. ⟨10.1212/WNL.0000000000201029⟩. ⟨hal-03776286⟩



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