Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Nov:103:106691.
doi: 10.1016/j.msard.2025.106691. Epub 2025 Aug 15.

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

Gabriel Bsteh  1 , Vincenzo Introcaso  2 , Christiane Gradl  3 , Gerhard Traxler  4 , Robert Barket  5 , Fabian Föttinger  1 , Helly Noemi Hammer  2 , Nik Krajnc  1 , Markus Ponleitner  1 , Tobias Zrzavy  1 , Florian Deisenhammer  5 , Franziska Di Pauli  5 , Andrew Chan  2 , Thomas Berger  1 , Robert Hoepner  2 , Harald Hegen  6
Affiliations
Free article

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

Gabriel Bsteh et al. Mult Scler Relat Disord. 2025 Nov.
Free article

Abstract

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.

Keywords: De-escalation; Discontinuation; Disease modifying therapy; Multiple sclerosis; Reactivation; Risk.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest Gabriel Bsteh: has participated in meetings sponsored by, received speaker honoraria or travel funding from Biogen, Celgene/BMS, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva, and received honoraria for consulting Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme and Teva. He has received unrestricted research grants from Celgene/BMS and Novartis. Vincenzo Introcaso: received travel funding from Biogen. Christiane Gradl: has participated in meetings sponsored by or received honoraria (lectures, consultations) and/or travel funding from Alexion, Almirall, Biogen, Bristol-Myers-Squibb, d-Pharma, Horizon, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Gerhard Traxler: has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Alexion, Amgen/Horizon, Biogen, Celgene/BMS, Janssen, Lilly, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Robert Barket: has participated in meetings sponsored by or received travel grants from, Novartis, Janssen and Sanofi-Genzyme. Received honoraria from Biogen and Janssen. Fabian Föttinger: nothing to disclose. Helly Hammer: has received speaker/advisor honorary from Biogen, Janssen, Merck, and Teva. She received research support within the last 5 years from Biogen. She received travel grants from Biogen, Janssen, Merck, and Roche. Nik Krajnc: has participated in meetings sponsored by, received speaker honoraria or travel funding from Alexion, BMS/Celgene, Janssen, Merck, Novartis, Roche and Sanofi-Genzyme and held a grant for a Multiple Sclerosis Clinical Training Fellowship Programme from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). Markus Ponleitner: Has participated in meetings sponsored by, received speaker or consulting honoraria from Amicus and travel funding from Amicus, Merck, Novartis and Sanofi-Genzyme. Tobias Zrzavy: has participated in meetings sponsored by or received travel funding from Biogen, Merck, Novartis, Roche, Sanofi-Genzyme and Teva. Florian Deisenhammer: has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, Celgene/BMS, Horizon, Janssen, Laurea Group, Medwhizz, Merck, Novartis, Neuraxpharm, Roche, Sandoz, and Sanofi. Franziska Di Pauli: has participated in meetings sponsored by, received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene BMS, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. Her institution has received research grants from Roche. Andrew Chan: has received speakers’/board honoraria from Actelion (Janssen/J&J), Alexion, Almirall, Bayer, Biogen, Celgene (BMS), Merck KGaA (Darmstadt, Germany), Novartis, Roche, Sanofi-Genzyme, and Teva, all for hospital research funds. He received research support from Biogen, CSL Behring, Genzyme, and UCB, the European Union, and the Swiss National Foundation. Thomas Berger: has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for MS: Allergan, Bayer, Biogen, Bionorica, BMS/Celgene, Genesis, GSK, GW/Jazz Pharma, Horizon, Janssen, MedDay, Merck, Novartis, Octapharma, Roche, Sandoz, Sanofi-Genzyme, Teva and UCB. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Bayer, BMS/Celgene, Merck, Novartis, Roche, Sanofi-Genzyme, Teva) and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Bayer, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi-Genzyme, Teva. Robert Hoepner: has received speaker/advisor honorary from Alexion, Almirall, Biogen, Celgene/BMS, Janssen, Merck, Novartis, Roche, Sanofi-Genzyme, and Teva. He received research support within the last 5 years from Biogen, Celgene/BMS, Chiesi, Roche, Merck, and Sanofi. He also received research grants from the Swiss MS Society, the SITEM Insel Support Fund and is a member of the Advisory Board of the Swiss and International MS Society. He also serves as deputy editor in chief for Journal of Central Nervous System disease. All conflicts are not related to this work. Harald Hegen: has participated in meetings sponsored by, received speaker honoraria or travel funding from Bayer, Biogen, Celgene/BMS, Horizon, Janssen, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva, and received honoraria for acting as consultant for Biogen, Celgene/BMS, Novartis, Roche, Sanofi-Genzyme and Teva.

Substances

LinkOut - more resources