Predicting PML in natalizumab-treated patients: can we do better?
- 1Department of Neurology, University Hospital Basel, Basel, Switzerland
- 2Department of Biomedicine, University of Basel, Basel, Switzerland
- Correspondence to Professor Ludwig Kappos, Departments of Neurology and Biomedicine, University of Basel, Petersgraben 4, Basel 4031, Switzerland;
- Received 13 February 2013
- Revised 25 February 2013
- Accepted 26 February 2013
- Published Online First 20 April 2013
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 …