Longitudinal evolution of JC virus serological index in multiple sclerosis patients treated with natalizumab:...

The anti-JC virus (JCV) antibody index is an established biomarker for estimating the risk of progressive multifocal leukoencephalopathy (PML) in patients with multiple sclerosis (MS) treated with natalizumab. However, long-term real-world data regarding the stability of JCV serostatus, particularly from Latin American populations, remain limited.

To evaluate longitudinal changes in the anti-JC virus (JCV) antibody index and their association with clinical and radiological outcomes in patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab during a 10-year follow-up in a Mexican public health tertiary center.

We conducted a retrospective observational cohort study including 104 RRMS patients treated with natalizumab between 2014 and 2024 at a single tertiary center in Guadalajara, Mexico. Anti-JCV antibody index was measured using the STRATIFY JCV™ DxSelect ELISA assay. Longitudinal serological patterns were categorized as persistent positive, persistent negative, seroconversion, indeterminate-to-positive transition, or seroreversion. Clinical and radiological outcomes were compared between treatment-naïve and previously treated patients.

At baseline, 49 patients (47.1%) were treatment-naïve, and 55 (52.9%) had prior exposure to disease-modifying therapy. Overall, 42 patients (40.4%) were JCV seropositive, 49 (47.1%) seronegative, and 13 (12.5%) indeterminate. Median duration of natalizumab exposure was 5.2 years (IQR 3.1-7.4), and the median number of anti-JCV antibody determinations per patient was 8 (range 2-18). Persistent seropositivity (51.9%) and persistent seronegativity (37.5%) were the predominant longitudinal patterns. Seroconversion occurred in 6.7% of patients overall (4.1% naïve, 8.9% non-naïve), indeterminate-to-positive transition in 3.8%, and seroreversion in 1.0% of patients. No cases of progressive multifocal leukoencephalopathy were observed. Prior exposure to disease-modifying therapy, age at natalizumab initiation, and baseline disability were not associated with longitudinal serological evolution. Treatment-naïve patients exhibited fewer relapses (p = 0.0026), lower MRI activity (p = 0.03), and higher NEDA-3 rates (64.6% vs 32.7%, p = 0.002), whereas long-term disability outcomes did not differ significantly between groups.

In this decade-spanning real-world cohort from a Latin American public health setting, anti-JCV antibody status remained predominantly stable during prolonged natalizumab therapy, confirming patterns previously reported in other populations. These findings add regional real-world evidence to the existing literature and support continued longitudinal serological monitoring. Early treatment initiation improved inflammatory disease control but did not significantly modify long-term disability trajectories.