008\u2005Disease reactivation after cessation of disease-modifying therapy in relapsing-remitting multiple sclerosis

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 18 029 eligible treatment discontinuation epochs were identified for seven therapies. Rates of relapse started to increase 2-months after natalizumab cessation. Commencement of a subsequent therapy within 2-4 months reduced the magnitude of disease reactivation. After discontinuation of fingolimod, rates of relapse increased overall, and stabilised faster in patients who started a new therapy within 1-2 months. 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, CI 0.72-0.81) and disability accumulation (0.73, 0.65-0.80). Conclusion Understanding the rate of disease reactivation after discontinuing different MS immunotherapies will help guide optimal wash-out times for therapeutic agents during treatment sequencing.