Risk stratification for disease reactivation after therapy de-escalation/discontinuation in relapsing multiple sclerosis by the VIAADISC score

OBJECTIVE: To investigate whether the VIAADISC score predicts disease reactivation in relapsing multiple sclerosis (RMS) after de-escalation/discontinuation of disease-modifying-therapy (DMT) METHODS: We included RMS patients who i) received any DMT other than interferon-beta or glatiramer-acetate ≥12 months, ii) de-escalated/discontinued DMT, iii) had MRI before de-escalation/discontinuation, and iv) had ≥12 months of follow-up. VIAADISC score (0-6; age <45/45-54/≥55 = 2/1/0 points, MRI activity = 2 points, duration without clinical disease activity <4/4-8/>8 years = 2/1/0 points) was calculated. The primary endpoint was disease reactivation (relapse and/or disability progression).

RESULTS: Of 129 RMS patients included (65.1 % females), 44.2 % had received natalizumab (NTZ), 19.4 % dimethylfumarate (DMF), 17.1 % teriflunomide (TERI), 14.0 % fingolimod (FTY) and 5.4 % rituximab (RTX). At de-escalation/discontinuation, mean age was 44.3 years (12.3), median duration of clinical stability 2.4 years (IQR1.5-3.9) and 93.1 % were without MRI activity, resulting in median VIAADISC score of 3 (IQR 2-4). Over median 6.0 years, disease reactivation reoccurred in 55.0 %, most frequently after NTZ/FTY discontinuation (73.3 %). In Cox regression, risk of disease reactivation was independently predicted by higher VIAADISC scores (HR 1.25 per point [95 % CI 1.03-1.53], p = 0.028) and de-escalation from FTY/NTZ (HR 2.20 [CI 1.18-4.10], p = 0.013). No disease reactivation was observed when DMF/TERI were discontinued with VIAADISC <2.

INTERPRETATION: Risk of disease reactivation after discontinuation from DMF/TERI can be stratified with the VIAADISC score and appears to be safe above age 45-55 and with long-lasting stability. However, risk after de-escalation from NTZ/FTY is too high to allow reliable stratification and should be avoided by lateral switch.