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Predicting PML in natalizumab-treated patients: can we do better?
  1. Tobias Derfuss1,2,
  2. Ludwig Kappos1,2
  1. 1Department of Neurology, University Hospital Basel, Basel, Switzerland
  2. 2Department of Biomedicine, University of Basel, Basel, Switzerland
  1. Correspondence to Professor Ludwig Kappos, Departments of Neurology and Biomedicine, University of Basel, Petersgraben 4, Basel 4031, Switzerland; Ludwig.Kappos{at}

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Longitudinal monitoring of JCV  antibodies as an aid in diagnosing of PML?

Patients treated with natalizumab for active relapsing–remitting multiple sclerosis (MS) benefit from its high efficacy and excellent tolerability; this was shown in the pivotal studies1 ,2 and has been confirmed by several prospective and retrospective observational studies in real-life settings.3 ,4 Though, treated patients and prescribing physicians alike are threatened by the low but over the years increasing risk of progressive multifocal leucoencephalopathy (PML). As of 2 January 2013, worldwide statistics of the manufacturer documented 323 confirmed cases out of approximately 108 300 patients with MS and Crohn's disease exposed to natalizumab. Although natalizumab-associated PML is less frequently lethal, most of the affected patients develop severe and permanent disability that adds to the burden of MS.5 A more favourable prognosis is clearly related to an early detection of PML and reconstitution of immune surveillance. Therefore, there is obviously a high need for reliable risk stratification, early detection and, if possible, prevention of PML.

Detection of anti-John Cunningham virus (JCV) antibodies in the blood has been proposed as the strongest risk predictor based on large studies allowing to predict a risk of less than 0.09 in 1000 patients negative for anti-JCV, and a risk of 2.86–4.96 per 1000 patients for those who have detectable levels of Abs against JCV with or without additional risk factors (duration of treatment, previous exposure to …

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  • Contributors Both TD and LK contributed in drafting the manuscript.

  • Competing interests TD serves on scientific advisory boards for Novartis Pharma, Merck Serono, Biogen Idec, Genzyme, Mitsubishi Pharma and Bayer Schering Pharma. He has received funding for travel and/or speaker honoraria from Biogen Idec, Novartis, Merck Serono, and Bayer Schering Pharma; and receives research support from Novartis Pharma, Merck Serono, the German Research Foundation, the European Union and the Swiss MS Society. LK has participated in the last 24 months as principal investigator, member or chair of planning and steering committees or advisory boards in corporate-sponsored clinical trials in multiple sclerosis and other neurological diseases. The sponsoring pharmaceutical companies for these trials include Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, Biotica, CLC Behring, Elan, Genmab, GeNeuro SA, Genmark, GlaxoSmithKline, Genzyme, Johnson & Johnson, Lilly, Merck Serono, Novartis, Novonordisk, Octapharma, Peptimmune, Roche, sanofi-aventis, Santhera, Teva, UCB, Xenoport and Wyeth. L. Kappos also lectured at medical conferences or in public on various aspects of the diagnosis and management of multiple sclerosis. In many cases, these talks have been sponsored by non-restricted educational grants to his institution from one or the other above-listed companies. Honoraria and other payments for all these activities have been exclusively used for funding of research of his department. Research and the clinical operations (nursing and patient care services) of the MS Center in Basel have been supported by non-restricted grants from one or more of these companies and by grants from the Swiss MS Society, the Swiss National Research Foundation, the European Union, the Gianni Rubatto, Novartis and Roche Research Foundations.

  • Provenance and peer review Commissioned; externally peer reviewed.

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