UK Experts Publish Guidance on JC Virus Testing for Natalizumab Biosimilar Tyruko

To address growing uncertainty over JC virus (JCV) antibody testing for patients receiving the natalizumab biosimilar Tyruko, a group of UK neurologists has published new recommendations in Multiple Sclerosis and Related Disorders.¹ The consensus statement provides a framework for interpreting JCV results and managing progressive multifocal leukoencephalopathy (PML) risk amid reports that the assays used for biosimilar monitoring may yield differing results from those historically used with the originator drug, Tysabri.

UK neurologists release new guidelines for JCV testing in patients using the natalizumab biosimilar Tyruko, addressing safety and monitoring challenges. | Image credit: millaf - stock.adobe.com

The discussion around the rollout of Tyruko and the challenges in aligning testing protocols comes as the global community observes Global Biosimilars Week, an annual initiative highlighting the importance of expanding access to safe, effective, and affordable biologic therapies.² The UK experience with natalizumab biosimilar testing underscores how the practical details of biosimilar implementation—such as laboratory assay consistency—play a critical role in ensuring that these therapies meet their promise of broader access while maintaining patient confidence and safety.¹

Reference natalizumab (Tysabri) is a well-established therapy for individuals with rapidly evolving severe multiple sclerosis (MS). The biosimilar version, Tyruko, was approved by the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) following evidence demonstrating equivalent efficacy and safety. Its introduction is expected to deliver cost savings and improve treatment access across the National Health Service (NHS).

However, a new challenge has emerged in the transition from the reference product to its biosimilar counterpart. JCV antibody testing, which is required for all patients receiving natalizumab due to the therapy’s risk of PML, has historically been conducted using Biogen’s Stratify JCV assay. For those receiving Tyruko, JCV status is now determined using Sandoz’s Immunowell assay, and studies have shown that the 2 tests may not always agree.

According to the researchers from Queen Mary University of London, “The Immunowell test appears more likely to report a positive JCV index compared with the Stratify assay.” While negative results between the 2 assays generally align, early data show that roughly 41% of patients have been reclassified from JCV-negative to JCV-positive when switching assays. This is a sharp contrast to the typical 3% to 6% annual seroconversion rate seen with Stratify alone.

This finding has implications for both clinical practice and patient well-being. People identified as JCV-positive are typically considered at higher risk of developing PML, which can prompt clinicians to shorten treatment duration, increase magnetic resonance imaging (MRI) monitoring frequency, or recommend alternative disease-modifying therapies. “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,” the authors wrote.

To help clinicians navigate these discrepancies, the group developed an interim set of principles for interpreting Immunowell results. The recommendations vary depending on whether a patient is new to natalizumab or switching from the reference product.

For treatment-naive patients starting on Tyruko, those with negative Immunowell results can be monitored using standard NHS protocols. Patients testing positive can generally proceed with therapy, particularly during the first 2 years, if risk is regularly reassessed and plans are made to transition or reduce risk exposure after 12 to 24 months. Extended-interval dosing or increased MRI monitoring may also be considered as risk-mitigation strategies, though supporting evidence remains limited.

For individuals transitioning from Tysabri to Tyruko, the panel advised that low-positive results on Immunowell should be interpreted cautiously, as short-term risk is unlikely to have changed significantly. Persistently positive or rising JCV indices after 6 months may, however, justify treatment review or modification after 12 to 24 months. Patients whose Immunowell results show unexpectedly high JCV indices should be counseled about the possibility of increased risk, though the authors noted that this remains “an area of clinical uncertainty.”

The statement emphasized that transparent communication between clinicians and patients will be key to maintaining trust as these testing transitions continue. “To maintain confidence in treatment decisions, shared decision-making is essential, including openly discussing both the benefits and risks of therapy,” the authors wrote.

The authors also pointed to broader structural issues in how biosimilars are integrated into health care systems. Because JCV testing is tied to proprietary pharmaceutical company assays, differences in available testing methods can create inconsistencies when switching to a biosimilar. The authors argued that “a publicly developed, standardized JCV assay would ensure uniform, reliable results across biosimilar preparations,” a step they say would promote equitable access and ensure consistent safety monitoring.

The statement’s limitations reflect the current lack of longitudinal data connecting Immunowell results to PML outcomes. Given the rarity of PML, building such evidence will take years. Until then, the authors recommend caution in directly applying existing Stratify-based risk models to Immunowell data, as this could overestimate risk and undermine confidence in biosimilar safety.

Despite these uncertainties, the authors reaffirmed their support for biosimilars as a path toward a more sustainable and accessible health care system. “Biosimilars offer an opportunity for more cost-effective health services, but their rollout has the potential to highlight vulnerabilities in service delivery models,” they concluded. “It is incumbent on regulators, pharmaceutical companies, clinical teams, and commissioning bodies to work together to ensure ongoing access to a highly effective therapy while maintaining patient safety.”

As Global Biosimilars Week spotlights efforts to increase biosimilar adoption and understanding worldwide, the UK’s experience with natalizumab biosimilar testing serves as a reminder that successful implementation requires not only regulatory approval and pricing reform but also consistent, evidence-based clinical tools to guide patient care.

References

1. Dobson R, Arun T, Varley J, et al. Approach to JCV testing with natalizumab biosimilar: a UK consensus statement. Mult Scler Relat Disord. Published online August 2025. doi:10.1016/j.msard.2025.106541
2. Global Biosimilars Week. Event official website. Accessed November 4, 2025. https://globalbiosimilarsweek.org/2025/