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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.
Glossary
- ARR=
- annualized rate of relapse;
- DMT=
- disease-modifying therapy;
- EDMUS=
- European Database for Multiple Sclerosis;
- EDSS=
- Expanded Disability Status Scale;
- MS=
- multiple sclerosis;
- OFSEP=
- Observatoire Français de la Sclérose en Plaques
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editors were Elizabeth Silbermann, MD, and Brad Worrall, MD, MSc, FAAN.
MSBase and OFSEP coinvestigators are listed in Appendix 2 at links.lww.com/WNL/C251.
Class of Evidence: NPub.org/coe
Infographic: NPub.org/ig9917
- Received November 5, 2021.
- Accepted in final form June 13, 2022.
- © 2022 American Academy of Neurology
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