title: No evidence of JC virus reactivation in natalizumab treated multiple sclerosis patients: an 18 month follow-up study.
abstract: OBJECTIVE
  Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MS patients treated with natalizumab over 18 months, and followed by a thorough monitoring programme.
  
  
  METHODS
  42 patients (F/M: 24/18, mean age 34.4±8.9 years) were followed-up by: urine and plasma JCV-DNA PCR assay, immune cell subsets analysis, clinical and MRI evaluation, quality of life, fatigue and mood assessment.
  
  
  RESULTS
  JCV data. At baseline, 11/42 (26%) patients had JCV viruria, persistent at serial controls. One patient acquired viruria at month 1 and one patient at month 12. No patient had JCV viraemia at baseline; three patients acquired viraemic (one at month 6, one at month 13 (both transiently) and one at month 12 (persistently viraemic)). The prevalence of JCV in both urine and plasma did not change significantly from baseline to months 12 and 18. No patient had clinical or MRI evidence of PML. Immunological data. Circulating B cells showed greater expansion (300% increase in absolute number) since the first infusion. NK cell count doubled with no change in percentage while T cell count increased with a reduced percentage, reflecting a clear redistribution in the lymphocyte compartment. CD4+ and CD8+ T cells increased proportionally, with no change in their percentage. Clinical data. 27 patients (64%) were disease free after 1 year. A marked improvement in quality of life was reported by 72% of patients.
  
  
  CONCLUSIONS
  No evidence of subclinical JCV reactivation was found in our natalizumab treated MS patients up to 18 months of therapy, notwithstanding the marked increase in circulating B cells observed. Moreover, the efficacy of natalizumab, its tolerability and the positive impact on quality of life were confirmed in this study.
authors.affiliation: Department of Neuroscience, Multiple Sclerosis Centre, First Clinic of Neurology, University Hospital of Padova, Padova, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Rinaldi
authors.forename: Francesca
authors.initials: F
authors.lastname: Rinaldi
authors.forename: Paola
authors.initials: P
authors.lastname: Perini
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Calabrese
authors.forename: Dario
authors.initials: D
authors.lastname: Seppi
authors.forename: Paola
authors.initials: P
authors.lastname: Grossi
authors.forename: Irene
authors.initials: I
authors.lastname: Mattisi
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.forename: Carlo
authors.initials: C
authors.lastname: Mengoli
authors.forename: Mariella
authors.initials: M
authors.lastname: Sanzari
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palú
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016516:CD4-CD8 Ratio; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007577:JC Virus / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology; D000069442:Natalizumab; D011788:Quality of Life; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab