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. 2021 May;28(5):1609-1616.
doi: 10.1111/ene.14705. Epub 2021 Jan 18.

Quantifying the risk of disease reactivation after interferon and glatiramer acetate discontinuation in multiple sclerosis: The VIAADISC score

Gabriel Bsteh  1 , Harald Hegen  2 , Katharina Riedl  1 , Patrick Altmann  1 , Michael Auer  2 , Klaus Berek  2 , Franziska Di Pauli  2 , Rainer Ehling  3 , Barbara Kornek  1 , Tobias Monschein  1 , Walter Rinner  1 , Christiane Schmied  1 , Sebastian Wurth  4 , Karin Zebenholzer  1 , Anne Zinganell  2 , Tobias Zrzavy  1 , Gudrun Zulehner  1 , Florian Deisenhammer  2 , Paulus Rommer  1 , Fritz Leutmezer  1 , Thomas Berger  1
Affiliations

Quantifying the risk of disease reactivation after interferon and glatiramer acetate discontinuation in multiple sclerosis: The VIAADISC score

Gabriel Bsteh et al. Eur J Neurol. 2021 May.

Abstract

Background and purpose: There is a lack of evidence guiding discontinuation of disease-modifying therapy (DMT) in relapsing multiple sclerosis (RMS). Thus, the objective of this study was to generate and validate a risk score for disease reactivation after DMT discontinuation in RMS.

Methods: We drew a generation and validation dataset from two separate prospectively collected observational databases including RMS patients who received interferon-β or glatiramer acetate for ≥12 months, then discontinued DMT for ≥6 months and had ≥2 years of follow-up available. In the generation sample (n = 168), regression analysis was performed to identify clinical or magnetic resonance imaging (MRI) variables independently predicting disease reactivation after DMT discontinuation. A predictive score was calculated using the variables included in the multivariable model and applied to the validation sample (n = 98).

Results: The variables included in the final model as independent predictors of disease reactivation were age at discontinuation, MRI activity at discontinuation, and duration of clinical stability (all p < 0.001). The resulting score was able to robustly identify patients at high (83%-85%), moderate (36%-38%), and low risk (7%) of disease reactivation within 5 years after DMT discontinuation in both cohorts.

Conclusions: The composite VIAADISC score is a valuable tool to inform and support patients and neurologists in the process of decision making to discontinue injectable DMTs.

Keywords: discontinuation; disease-modifying therapy; multiple sclerosis; reactivation; risk AUTHOR: Please check the list of abbreviations..

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Conflict of interest statement

Gabriel Bsteh has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Celgene, Lilly, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva, and received honoraria for consulting from Biogen, Celgene, Roche, and Teva. Harald Hegen has participated in meetings sponsored by or received speaker honoraria or travel funding from Bayer, Biogen, Merck, Novartis, Sanofi‐Genzyme, Siemens, and Teva, and received honoraria for consulting from Biogen and Teva. Katharina Riedl reports no disclosures. Patrick Altmann has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Merck, Roche, Sanofi‐Genzyme, and Teva, and received honoraria for consulting from Biogen. He received a research grant from Quanterix International and was awarded a combined sponsorship from Biogen, Merck, Roche, Sanofi‐Genzyme, and Teva for a clinical study. Michael Auer received speaker honoraria and/or travel grants from Biogen, Merck, Novartis, and Sanofi‐Genzyme. Klaus Berek has participated in meetings sponsored by and received travel funding from Roche. Franziska Di Pauli has participated in meetings sponsored by or received honoraria (lectures, advisory boards, consultations) or travel funding from Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. Rainer Ehling has participated in meetings sponsored by or received speaker honoraria or travel funding from Biogen, Böhringer Ingelheim, Celgene, Daiichi Sankyo, Merck, Novartis, Ottobock, and Teva. Barbara Kornek has received speaking honoraria or travel support from Biogen, Celgene, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva and gives advice to Biogen, Celgene, Merck, Novartis, Roche, and Sanofi‐Genzyme. Tobias Monschein has participated in meetings sponsored by or received travel funding from Biogen, Celgene, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. Walter Rinner has received travel funding from Bayer, Biogen, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. Christiane Schmied has received speaking honoria and travel support from Biogen, Merck, Sanofi‐Genzyme, and Teva. Sebastian Wurth has participated in meetings sponsored by or received honoraria or travel funding from Allergan, Biogen, Ipsen Pharma, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. Anne Zinganell has participated in meetings sponsored by or received speaking honoraria or travel funding from Biogen, Merck, Sanofi‐Genzyme, and Teva. Karin Zebenholzer received speaking honoraria or travel grants from Biogen, 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. Gudrun Zulehner 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 from Alexion, Almirall, Biogen, Celgene, Merck, Novartis, Roche, and Sanofi‐Genzyme. His institution received scientific grants from Biogen and Sanofi‐Genzyme. Paulus Rommer has received honoraria for consultancy/speaking from AbbVie, Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sandoz, and Sanofi‐Genzyme, and has received research grants from Amicus, Biogen, Merck, and Roche. Fritz Leutmezer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer, Biogen, Celgene, MedDay, Merck, Novartis, Roche, Sanofi‐Genzyme, and Teva. Thomas Berger has participated in meetings sponsored by and received honoraria (lectures, advisory boards, consultations) from pharmaceutical companies marketing treatments for multiple sclerosis: Allergan, Almirall, Bayer, Biogen, Biologix, Bionorica, Celgene, MedDay, Merck, Novartis, Octapharma, Roche, Sanofi‐Genzyme, Teva, and TG Pharmaceuticals. His institution has received financial support in the past 12 months by unrestricted research grants (Biogen, Merck, Novartis, Sanofi‐Genzyme, Teva and for participation in clinical trials in multiple sclerosis sponsored by Alexion, Biogen, Merck, Novartis, Octapharma, Roche, Sanofi‐Genzyme, and Teva.

Figures

FIGURE 1
FIGURE 1
Inclusion flowchart of the generation (a) and the validation (b) cohorts. DMT, disease‐modifying therapy; IMSD, Innsbruck Multiple Sclerosis Database; MRI, magnetic resonance imaging; MS, multiple sclerosis; VMSD, Vienna Multiple Sclerosis Database.
FIGURE 2
FIGURE 2
Probability of disease reactivation after DMT discontinuation stratified according to VIAADISC score in the generation cohort (a, b) and in the validation cohort (c, d). Vertical dotted line marks the time point 5 years after disease‐modifying therapy (DMT) discontinuation used for calculation of probability of disease reactivation. Horizontal dotted lines indicate the 33rd and 67th percentile of probability of disease reactivation. Groups significantly differed in all four graphs (p < 0.001, calculated by log‐rank test for trend)
See this image and copyright information in PMC

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