Zusammenfassung
Die JC-Virus (JCV)-assoziierte progressive multifokale Leukenzephalopathie (PML) ist eine schwerwiegende unerwünschte Arzneimittelwirkung, die unter der Behandlung einer Multiplen Sklerose (MS) mit Natalizumab (Tysabri®) in seltenen Fällen auftreten kann. Neben den bekannten Risikofaktoren – Behandlungsdauer über 24 Monate hinaus sowie eine vorangegangene immunsuppressive Therapie – wurde nun auch eine serologische Untersuchung zum Nachweis sog. Anti-JCV-Antikörper zur Risikostratifizierung in den Zulassungstext der Substanz mit aufgenommen. Unzweifelhaft stellt die JCV-Serologie ein Werkzeug zur PML-Risiko-Stratifzierung von MS-Patienten unter Natalizumab-Therapie dar. Die bisherige Datenlage und die wissenschaftlichen Entwicklungen zur Validität des Assays wurden bisher aber nicht unabhängig bestätigt.
Der vorliegende Artikel erläutert daher Möglichkeiten und Grenzen einer solchen Untersuchung und gibt auf der Basis des zur Verfügung stehenden Wissens konkrete Empfehlungen für die klinische Anwendung dieser neuen Untersuchung.
Summary
JC virus (JCV)-associated progressive multifocal leukoencephalopathy (PML) represents a rare but serious side effect of natalizumab (Tysabri®) in the treatment of patients with relapsing forms of multiple sclerosis (MS). Two factors that may increase the risk of PML have been identified: treatment duration beyond 24 months and prior immunosuppressive therapy. Recently determination of anti-JCV antibodies mirroring JCV infection has allowed a third factor to be added to this list, and a positive serological test has been included as a risk factor on the label of natalizumab. Clearly, JCV serology represents a tool for PML risk stratification in MS patients treated with natalizumab. However, current data as well as the experimental development of the underlying assay have not been validated by an independent laboratory.
The present article discusses possibilities and challenges of this assay and, based on our present knowledge, provides recommendations for the clinical implementation in daily practice.
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Literatur
Warnke C, Adams O, Gold R et al (2011) Progressive multifokale Leukoenzephalopathie unter Natalizumab: Erste Möglichkeiten einer Risikostratifizierung? Nervenarzt (Epub ahead of print)
Gorelik L, Lerner M, Bixler S et al (2010) Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol 68:295–303
West TW, Cree BA (2010) Natalizumab dosage suspension: are we helping or hurting? Ann Neurol 68:395–399.
Kaufman MD, Lee R, Norton H (2011) Course of relapsing-remitting multiple sclerosis before, during and after natalizumab. Mult Scler 17(4):490–494
Sandrock A, Hotermans C, Richman S et al (2011) Risk Stratification for progressive multifocal leukoencephalopathy (PML) in MS patients: role of prior immunosuppressant use, natalizumab-treatment duration, and anti-JCV antibody status. Neurology 76(Suppl 4) P03.248
Verbeeck J, Van Assche G, Ryding J et al (2008) JC viral loads in patients with Crohn’s disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy? Gut 57:1393–1397
Stolt A, Sasnauskas K, Koskela P et al (2003) Seroepidemiology of the human polyomaviruses. J Gen Virol 84:1499–1504
Kean JM, Rao S, Wang M, Garcea RL (2009) Seroepidemiology of human polyomaviruses. PLoS Pathog 5:e1000363
Egli A, Infanti L, Dumoulin A et al (2009) Prevalence of polyomavirus BK and JC infection and replication in 400 healthy blood donors. J Infect Dis 199:837–846
Knowles WA, Pipkin P, Andrews N, et al (2003) Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40. J Med Virol 71:115–123
Matos A, Duque V, Beato S et al (2010) Characterization of JC human polyomavirus infection in a Portuguese population. J Med Virol 82:494–504
Goelz SE, Gorelik L, Subramanyam M (2010) Assay design and sample collection can affect anti-John Cunningham virus antibody detection. Ann Neurol 68(3):304–310
Cohen JA, Barkhof F, Comi G et al (2010) Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 362:402–415
Kappos L, Radue EW, O’Connor P et al (2010) A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 362: 387–401
Aktas O, Ingwersen J, Kieseier BC et al (2011) Orales Fingolimod bei Multipler Sklerose. Therapeutische Modulation des Sphingosin-1-Phosphat-Systems. Nervenarzt 82:215–225
www.whocc.no/atc_ddd_index/?code=L04AA
Mehling M, Johnson TA, Antel J et al (2011) Clinical immunology of the sphingosine 1-phsophate receptor modulator fingolimod (FTY720) in multiple sclerosis. Neurology 76(Suppl 3):20–27
Kowarik MC, Pellkofer HL, Cepok S et al (2011) Differential effects of fingolimod (FTY720) on immune cells in the CSF and blood of patients with MS. Neurology 76:1214–1221
Tan CS, Koralnik IJ (2010) Progressive multifocal leukoencephalopathy and other disorders caused by JC virus- clinical features and pathogenesis. Lancet Neurol 9:425–437
Warnke C, Menge T, Hartung HP et al (2010) Natalizumab and progressive multifocal leukoencephalopathy what are the causal factors and can it be avoided? Arch Neurol 67:923–930
Haghikia A, Perrech M, Pula B et al (2011) Functional energetics of CD4+-cellular immunity in monoclonal antibody-associated progressive multifocal leukoencephalopathy in autoimmune disorders. PLoS One (in press)
O’Connor PW, Goodman A, Kappos L et al (2011) Disease activity return during natalizumab treatment interruption in patients with multiple sclerosis. Neurology (Epub ahead of print)
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Warnke, C., Adams, O., Hartung, H. et al. Risikostratifizierung einer progressiven multifokalen Leukenzephalopathie unter Natalizumab. Nervenarzt 82, 1314–1319 (2011). https://doi.org/10.1007/s00115-011-3319-2
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DOI: https://doi.org/10.1007/s00115-011-3319-2