Approach to JCV testing with natalizumab biosimilar: a UK consensus statement.

Biosimilars have an important role to play in healthcare, with the potential to reduce costs and widen access to treatment. We welcome the use of biosimilars in the treatment of multiple sclerosis. Serological testing for JC virus is mandated as part of safety monitoring in those treated with natalizumab. All PML risk stratification data to date has come from the use of the "Stratify" JC virus (JCV) serostatus test. The "Immunowell" test used to define JCV serostatus (used with Tyruko) does not always give equivalent results to the Stratify test (used with Tysabri), particularly around thresholds used to define risk of progressive multifocal leukoencephalopathy (PML). In comparison to the Stratify test, Immunowell appears more likely to report a positive JCV index. However, negative results using Immunowell show a high rate of agreement with Stratify, which allows for a rational safety strategy. There remains a real risk that a proportion of patients will be inappropriately classified as being at higher risk of PML, and therefore denied the option of natalizumab, a highly effective therapy, or undergo unnecessarily burdensome monitoring, with resultant cost to the NHS and anxiety. We provide guidance for patients with discordant results between assays, aiming to balance the need for rigorous safety monitoring with patient access to highly effective therapy and unnecessary monitoring burden on healthcare services.