Changes in Anti-JCV Antibody Status in a Large Population of Multiple Sclerosis Patients Treated with Natalizumab

Introduction: Natalizumab (NTZ) can be associated with an opportunistic infection, progressive multifocal leukoencephalopathy (PML), caused by John Cunningham virus (JCV). High titer of anti-JCV antibody (JCV index) in patients treated with NTZ for over 2 years limit it use, leading to treatment discontinuation. Objective: Aim of the study was to investigate the JCV index changes pre, during and post NTZ treatment and describe the trend after a long period of NTZ discontinuation. Methods: Patients with relapsing–remitting multiple sclerosis (RR–MS) treated with NTZ between 2010 and 2018 were enrolled in this retrospective-prospective observational study. Inclusion criteria were: (1) diagnosis of RR–MS according to the McDonald criteria 2010, (2) at least six NTZ administrations, (3) at least two determinations of JCV Index during the follow-up period, (4) NTZ discontinuation period for more than 6 months. JCV index was determined by STRATIFY II. There were three different timepoints: NTZ initiation (T0), NTZ discontinuation (T1) and time after NTZ suspension (T2). Seroconversion was defined as changing status of serum JCV antibody. Main outcomes were the JCV index changes and the rate of seroconversion. Results: At baseline we enrolled 285 patients (208 JCV negative, 67 JCV positive, and 10 not available). There was a statistically significant increase of JCV index during NTZ treatment period (T0 vs T1, p =0.0009) and during NTZ discontinuation period (T1 vs T2, p =0.04). Patients seroconverted to a positive status more frequently during NTZ treatment than after discontinuation (p =0.008). Moreover, patients who shifted to fingolimod (FTY) as exit strategy after NTZ discontinuation, showed a statistically significant increase of JCV index. Conclusion: Our data confirmed that a high percentage of patients shift to or remain in a positive JCV status during NTZ treatment and after discontinuation. NTZ suspension seems not to be able to interfere on JCV status modification over an extended period. The choice of alternative treatment as exit strategy after NTZ discontinuation should be carefully considered because it could negatively influence the PML risk stratification of patients.