TY - JOUR
T1 - Disease Reactivation After Cessation of Disease-Modifying Therapy in Patients With Relapsing-Remitting Multiple Sclerosis
AU - MSBase and OFSEP
AU - Roos, Izanne
AU - Malpas, Charles
AU - Leray, Emmanuelle
AU - Casey, Romain
AU - Horakova, Dana
AU - Havrdova, Eva Kubala
AU - Debouverie, Marc
AU - Patti, Francesco
AU - De Seze, Jerome
AU - Izquierdo, Guillermo
AU - Eichau, Sara
AU - Edan, Gilles
AU - Prat, Alexandre
AU - Girard, Marc
AU - Ozakbas, Serkan
AU - Grammond, Pierre
AU - Zephir, Helene
AU - Ciron, Jonathan
AU - Maillart, Elisabeth
AU - Moreau, Thibault
AU - Amato, Maria Pia
AU - Labauge, Pierre
AU - Alroughani, Raed
AU - Buzzard, Katherine
AU - Skibina, Olga
AU - Terzi, Murat
AU - Laplaud, David Axel
AU - Berger, Eric
AU - Grand'Maison, Francois
AU - Lebrun-Frenay, Christine
AU - Cartechini, Elisabetta
AU - Boz, Cavit
AU - Lechner-Scott, Jeannette
AU - Clavelou, Pierre
AU - Stankoff, Bruno
AU - Prevost, Julie
AU - Kappos, Ludwig
AU - Pelletier, Jean
AU - Shaygannejad, Vahid
AU - Yamout, Bassem I
AU - Khoury, Samia J
AU - Gerlach, Oliver
AU - Spitaleri, Daniele L A
AU - Van Pesch, Vincent
AU - Gout, Olivier
AU - Turkoglu, Recai
AU - Heinzlef, Olivier
AU - Thouvenot, Eric
AU - McCombe, Pamela Ann
AU - Al-Asmi, Abdullah
N1 - © 2022 American Academy of Neurology.
PY - 2022/10/25
Y1 - 2022/10/25
N2 - 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.
AB - 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.
KW - Humans
KW - Female
KW - Multiple Sclerosis, Relapsing-Remitting/drug therapy
KW - Natalizumab/therapeutic use
KW - Fingolimod Hydrochloride/therapeutic use
KW - Multiple Sclerosis/chemically induced
KW - Retrospective Studies
KW - Recurrence
KW - Immunosuppressive Agents/adverse effects
U2 - 10.1212/WNL.0000000000201029
DO - 10.1212/WNL.0000000000201029
M3 - Article
C2 - 35977837
SN - 0028-3878
VL - 99
SP - e1926-e1944
JO - Neurology
JF - Neurology
IS - 17
ER -