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

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Abstract

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.

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Author notes

  1. Eleonora Sgarlata and Clara Grazia Chisari equally contributed.

Authors and Affiliations

  1. Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy

    Eleonora Sgarlata & Enrico Millefiorini

  2. Stroke Unit, Department of Medicine, Umberto I Hospital, Siracusa, Italy

    Eleonora Sgarlata

  3. Department “GF Ingrassia”, Section of Neurosciences, University of Catania, Via S. Sofia 78, 95129, Catania, Italy

    Clara Grazia Chisari, Emanuele D’Amico & Francesco Patti

Authors
  1. Eleonora Sgarlata
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  2. Clara Grazia Chisari
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  3. Emanuele D’Amico
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  4. Enrico Millefiorini
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  5. Francesco Patti
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Corresponding author

Correspondence to Francesco Patti.

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Funding

This study was not fonded.

Conflict of interest

Eleonora Sgarlata declares there is no conflict of interest. Clara G. Chisari declares there is no conflict of interest. Emanuele D’Amico declares there is no conflict of interest. Enrico Millefiorini received grants from Biogen, Merck Serono, Novartis Genzyme and Roche, consulting fees from Biogen, Merck Serono, Novartis Genzyme and Roche, travel support for congress participations from Biogen, Merck Serono, Novartis Genzyme and Roche; he also served as advisory board member for Bayer, Biogen, Merck Serono, Novartis Genzyme and Roche. Francesco Patti received grants from Almirall, Bayer, Biogen, Merck Serono, Novartis Genzyme, Teva and Roche, consulting fees from Biogen, Merck Serono, Novartis Genzyme and Roche, travel support for congress participations from Almirall, Biogen, Merck Serono, Novartis Genzyme, Teva and Roche; he also served as advisory board member for Almirall, Bayer, Biogen, Merck Serono, Novartis, Genzyme, Teva and Roche. He was also fonded by Pfizer and FISM for epidemiological studies.

Ethical approval

This study protocol was approved by the local Ethical Committee of the University of Catania (Catania 1).

Informed consent

Each patient participating to the study signed an Informed Consent specifically designed for the study.

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Sgarlata, E., Chisari, C.G., D’Amico, E. et al. Changes in Anti-JCV Antibody Status in a Large Population of Multiple Sclerosis Patients Treated with Natalizumab. CNS Drugs 34, 535–543 (2020). https://doi.org/10.1007/s40263-020-00716-6

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  • DOI: https://doi.org/10.1007/s40263-020-00716-6

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