Kappa Index predicts disease activity and transition to high-efficacy therapies in multiple sclerosis
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Simone Marcheselli
,
Francesco Corrado
Abstract
Objectives
The Kappa Index has proven its diagnostic value for multiple sclerosis (MS), while its prognostic potential remains to be fully explored. The objective of this study is thus to investigate the value of the Kappa Index at disease onset in predicting disease activity and high-efficacy therapy (HET) initiation.
Methods
We enrolled MS patients with available Kappa Index values at disease onset and a follow-up of at least two years. Primary outcome was the time to loss of NEDA3 (no evidence of disease activity-3) defined as the absence of relapses, MRI activity, and disability progression. Secondary outcome was the time to HET initiation.
Results
Of 120 enrolled patients (36 M, 84 F, mean age: 35 ± 11 years), NEDA3 loss occurred in 89 (74 %) by the end of the follow-up period. A total of 98 (82 %) initiated a moderate efficacy therapy (MET); of these, 34 (28 %) transitioned to a HET during follow-up. Kappa Index values above the maximally selected log-rank statistic-derived cut-off of 38 were independent risk factors for NEDA3 loss (HR 1.75, 95 % CI: 1.09–2.80, p=0.021) and HET initiation (3.25, 95 % CI: 1.54–6.87, p=0.002) and also independently predicted HET following MET failure (2.54, 95 % CI: 1.17–5.51, p=0.018).
Conclusions
Elevated Kappa Index values at diagnosis predict disease activity, MET failure and HET initiation and may be a valuable adjunctive tool in identifying patients in need of prompt HET initiation.
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Research ethics: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Area Vasta Emilia Nord Research Ethics Committee (approval no. 0035240/24) on December 11, 2024.
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Informed consent: Participants signed the relevant written informed consent for participation in the study, in the form approved by the Area Vasta Emilia Nord Ethical Committee.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. Conceptualization, D.F.; methodology, D.F.; software, S.M.; validation, D.F.; investigation, S.M.; data curation, A.F., K.S, G.D.N, F.G., M.C., F.V., S.M., F.C., P.N.; writing – original draft preparation, S.M., writing – review and editing, D.F., A.F., K.S., G.D.N., F.G., M.C., P.N., F.V. and F.C.; visualization, D.F.; supervision, D.F. All authors have read and agreed to the published version of the manuscript.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: D.F. has received travel grants and/or honoraria for speaking or advisory boards from Binding Site, which own the Optilite and Freelite assays used in this study, and from Alexion, Biogen, Merck, Novartis, Roche, Sanofi, which own the patent to the different MS drugs evaluated in this study. D.F. has also received travel grants and honoraria for speaking from Bristol-Myers-Squibb and Neuraxpharm. F.G. has received eraria for speaking from Alexion. F.V., S.M., F.C., P.N., A.F., K.S., G.D.N. and M.C. have nothing to disclose.
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Research funding: None declared.
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Data availability: The data that support the findings of this study will be made available from the corresponding author, D.F., upon reasonable request.
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Supplementary Material
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