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

Roos, Izanne Malpas, Charles Leray, Emmanuelle Casey, Romain Horakova, Dana Havrdova, Eva Kubala Debouverie, Marc Patti, Francesco De Seze, Jerome Izquierdo, Guillermo Eichau, Sara Edan, Gilles Prat, Alexandre Girard, Marc Ozakbas, Serkan Grammond, Pierre Zephir, Helene Ciron, Jonathan Maillart, Elisabeth Moreau, Thibault Amato, Maria Pia Labauge, Pierre Alroughani, Raed Buzzard, Katherine Skibina, Olga Terzi, Murat Laplaud, David Axel Berger, Eric Grand'Maison, Francois Lebrun-Frenay, Christine Cartechini, Elisabetta Boz, Cavit Lechner-Scott, Jeannette Clavelou, Pierre Stankoff, Bruno Prevost, Julie Kappos, Ludwig Pelletier, Jean Shaygannejad, Vahid Yamout, Bassem I Khoury, Samia J Gerlach, Oliver Spitaleri, Daniele L A Van Pesch, Vincent [UCL] Gout, Olivier Turkoglu, Recai Heinzlef, Olivier Thouvenot, Eric McCombe, Pamela Ann Soysal, Aysun Bourre, Bertrand Slee, Mark Castillo-Trivino, Tamara Bakchine, Serge Ampapa, Radek Butler, Ernest Gerard Wahab, Abir Macdonell, Richard A Aguera-Morales, Eduardo Cabre, Philippe Ben, Nasr Haifa Van der Walt, Anneke Laureys, Guy Van Hijfte, Liesbeth Ramo-Tello, Cristina M Maubeuge, Nicolas Hodgkinson, Suzanne Sánchez-Menoyo, José Luis Barnett, Michael H Labeyrie, Celine Vucic, Steve Sidhom, Youssef Gouider, Riadh Csepany, Tunde Sotoca, Javier de Gans, Koen Al-Asmi, Abdullah Fragoso, Yara Dadalti Vukusic, Sandra Butzkueven, Helmut Kalincik, Tomas MSBase and OFSEP et al.[show all]

(eng) 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.