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Comparative Study
. 2025 Jun;31(7):882-885.
doi: 10.1177/13524585251346652. Epub 2025 Jun 14.

A comparison of JC virus assay performance provided with originator and biosimilar natalizumab

James Varley  1 , Rahma Beyrouti  2 , Richard Nicholas  1 , Rachel Dorsey  1 , Wallace Brownlee  2 , David Paling  3 , Joela Mathews  4 , Ruth Dobson  4   5
Affiliations
Comparative Study

A comparison of JC virus assay performance provided with originator and biosimilar natalizumab

James Varley et al. Mult Scler. 2025 Jun.

Abstract

Background: A rare complication of natalizumab treatment is progressive multifocal leukoencephalopathy (PML); risk can be stratified using JC virus (JCV) antibody status. Risk calculators to aid clinical decision-making use cohort data tested using the Stratify-JCV assay. Following concerns of an increased number of JCV seropositive results following the switch to biosimilar natalizumab and the associated test switch, we sought to understand the clinical implications.

Methods: A total of 497 people with MS, who had switched from Tysabri to Tyruko with sequential results available on both assays, were included.

Results: Of 250 patients negative on Stratify-JCV, 119 (47.6%) were subsequently positive on ImmunoWELL. Agreement was the poorest at lower JCV index, where positive/negative cutoffs inform risk stratification and pharmacovigilance protocols most significantly.

Conclusion: These observed differences create uncertainty in how to counsel patients and best carry out PML surveillance. Specific concerns include overestimating risk leading to increased patient concern, increased monitoring burden and associated healthcare costs and lack of access to a highly effective therapy. It is incumbent on all stakeholders including pharmaceutical industry and test developers, patient groups, governmental authorities (including regulatory bodies) and clinicians to work together to find an expeditious solution.

Keywords: JCV; Multiple sclerosis; PML; risk.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: J.V. has received reimbursement for advisory boards, conference attendance and educational events from Merck, Novartis and Roche. R.B. has no acknowledgements. R.N. has received reimbursement for advisory boards from Roche and Novartis. R.D. has received reimbursement for advisory boards, conference attendance and educational events for Sanofi, Merck, Biogen, Novartis, Janssen and Roche. W.B. has received speaker honoraria and/or acted as a consultant for Biogen, Janssen, Merck, Novartis, Roche, Sandoz, Sanofi and Viatris. D.P. is principal investigator for commercial trials funded by Novartis, Merck, Janssen Pharmaceuticals and Roche; chief investigator for commercial trials funded by Novartis; has an investigator grant from Sanofi Genzyme; he has previously received advisory board/consultancy and speaker’s fees from Biogen, Celgene, Janssen, MedDay, Merck, Novartis, Roche and Sandoz. J.M. has Biogen, Janssen, Merck, Neurax, Novartis, Roche, Sandoz and Sanofi. RD has received honoraria for speaking and/or travelling from Biogen, Eisai, Merck, Roche and Janssen. Advisory boards for Roche, Biogen, Sandoz, Novartis and Merck in the past 2 years. All honoraria for speaking, travelling and advisory boards were paid into an institutional account and used to support research, open access publications and training for research group members. She has received grant support from Biogen, Merck and Celgene.

Figures

Figure 1.
Figure 1.
(a) Sankey plot of the JCV index stratification of patients via the Stratify assay on the left and how this relates to ImmunoWELL stratification on the right. Created using SankeyMATIC.com. (b) Bland–Altman plot of agreement between the two tests across the JCV index – with the poorest agreement seen at the lower levels of JCV testing. The mean (solid line) and upper and lower bounds of the 95% confidence interval (2 standard deviations) are also indicated.
See this image and copyright information in PMC

References

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