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Risk of secondary progression in patients with highly active multiple sclerosis treated with natalizumab: a real-life study

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Abstract

Background

one of the most important therapeutic goals in relapse-onset multiple sclerosis is to preclude conversion to secondary progression. Our objective was to determine the risk of progression associated with natalizumab treatment in an registry-based cohort of patients and to identify determinant factors.

Methods

Patients with relapse-onset multiple sclerosis from the Registre Lorrain des Scléroses en Plaques (ReLSEP) were included if they had received one infusion of natalizumab between 2002 and 2021. The risk of secondary progression was determined using a standardized definition and a multi-state estimator to account for the possibility of stopping natalizumab before progression, and analyzed with multivariate Cox models.

Results

574 patients were followed up for a median of 6.7 years. Of the 304 who stopped NTZ before progression onset, the probabilities (95% confidence interval) to convert to progression after 1, 2, 5 and 10 years were 3.2% (2.0–4.8%), 5.3% (3.6–7.3%), 17.5% (14.3–21.3%) and 28.3% (23.7–33.7%), respectively. Discontinuation of NTZ during follow-up was significantly associated with an increased risk of conversion in case of no resumption of a highly active treatment thereafter (adjusted hazard ratio = 2.7; 95% confidence interval 1.5–4.9; p = 0.001). The use of such a treatment was associated with a lower risk of progression (adjusted hazard ratio = 0.42; 95% confidence interval 0.23–0.79; p = 0.007).

Conclusion

the risk of conversion to secondary progression associated with natalizumab treatment is relatively low but increases in case of natalizumab discontinuation in the absence of switch to highly active immunosuppressant.

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Data availability

The data that support the findings of this study are available on request from the corresponding author, GM. The data are not publicly available because they contain information that could compromise the privacy of research participants.

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Acknowledgements

The authors thank the patients, the research nurses, clinical coordinators, technicians and statistics team for their contributions to patient care and conduct of the protocol.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Neurology, Nancy University Hospital, 54035, Nancy, France

    Louisa Scherer, Sophie Pittion-Vouyovitch, Marc Debouverie & Guillaume Mathey

  2. CIC, Epidémiologie Clinique, CHRU-Nancy, Université de Lorraine, 54000, Nancy, France

    Marc Soudant, Francis Guillemin & Jonathan Epstein

  3. Université de Lorraine, INSPIIRE, INSERM, 54000, Nancy, France

    Marc Debouverie, Francis Guillemin, Jonathan Epstein & Guillaume Mathey

Authors
  1. Louisa Scherer
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Corresponding author

Correspondence to Guillaume Mathey.

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Conflicts of interest

LS, JE, MS, SPV, MD and GM declare that there is no conflict of interest in line with this work. FG reports grants from Roche, Merck and Biogen to his institution.

Ethical statement

All patients gave their informed consent to participate in epidemiological research. Data collection was approved by the French National Commission for Data Protection and Liberties (CNIL n° 913,001), and confidentiality and safety of the data were ensured in accordance with their recommendations.

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Scherer, L., Soudant, M., Pittion-Vouyovitch, S. et al. Risk of secondary progression in patients with highly active multiple sclerosis treated with natalizumab: a real-life study. J Neurol 271, 2216–2224 (2024). https://doi.org/10.1007/s00415-024-12266-8

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