title: High cumulative JC virus seroconversion rate during long-term use of natalizumab.
abstract: John Cunningham virus (JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing-remitting MS (RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing.
  
  
  
  In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti-JCV antibody indices were measured in 933 available samples. Eighty-six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow-up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow-up duration. No significant increase was seen in the anti-JCV antibody index in the non-converting patients during the follow-up.
  
  
  
  The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy.
authors.affiliation: Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Vennegoor
authors.affiliation: Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: van Rossum
authors.affiliation: Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Leurs
authors.affiliation: Department of Radiology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Landsteiner Laboratory, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Rispens
authors.affiliation: Department of Medical Microbiology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: J L A N
authors.initials: JL
authors.lastname: Murk
authors.affiliation: Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: B M J
authors.initials: BM
authors.lastname: Uitdehaag
authors.affiliation: Department of Neurology, MS Centre Amsterdam, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Killestein
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D007577:JC Virus / Q000276:immunology*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood / Q000139:chemically induced / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D000069078:Seroconversion
chemical_list: D000914:Antibodies, Viral; D007155:Immunologic Factors; D000069442:Natalizumab
keywords: JC virus; multiple sclerosis; natalizumab; progressive multifocal leukoencephalopathy