Natalizumab-associated progressive multifocal leucoencephalopathy: a practical approach to risk profiling and monitoring
- 1Department of Clinical Neurosciences, University of Edinburgh, Edinburgh, UK
- 2Department of Neuroscience and Trauma, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK
- Correspondence to Dr David Hunt, Clinical Lecturer in Neurology, Department of Clinical Neurosciences, University of Edinburgh, Chancellor's Building, Little France, Edinburgh, Midlothian, EH16 4SB, UK;
Contributors DPJH and GG are the main authors. This review has been prepared in close consultation and collaboration with the people listed as Collaborators.
- Received 2 August 2011
- Accepted 8 December 2011
Natalizumab reduces relapse frequency, delays onset of disease progression and improves disease outcomes in relapsing–remitting multiple sclerosis (MS) and is a cost-effective treatment for rapidly evolving severe relapsing–remitting MS. However, it is associated with the development of progressive multifocal leucoencephalopathy (PML), a serious opportunistic brain infection caused by a neurotropic strain of the JC virus (JCV). Until May 2011, 83 300 patients had received natalizumab for MS. One hundred and twenty-four patients had developed PML, of whom 23 (19%) died. In order to maximise the benefit–risk ratio of natalizumab for MS patients it is important to develop a strategy for risk profiling and monitoring for PML. Central to this is an understanding of the biology of the JCV and the emerging clinical picture of natalizumab-associated PML. This paper reviews the evidence for managing the risk of PML in natalizumab-treated patients and the authors propose an algorithm for risk profiling and risk management. Key features of this algorithm include risk stratification based on emerging risk factors, heightened clinical vigilance for the clinical features of natalizumab-associated PML and considerations for temporary and permanent cessation of natalizumab dosing.
Please see the end of the article for the list of collaborators and their affliations.
Competing interests GG has received personal compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from Bayer-Schering Healthcare, Biogen-Idec, Eisai, Elan, Fiveprime, Genzyme, Genentech, GSK, Ironwood, Merck-Serono, Novartis, Pfizer, Roche, Sanofi-Aventis, Synthon BV, Teva, UCB Pharma and Vertex Pharmaceuticals. DPJH has performed consultancy work for Biogen-Idec with all fees donated to local neurological research charities.
Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Neil Scolding, Bristol, UK