Progressive multifokale Leukenzephalopathie unter Natalizumab

Abstract

Natalizumab (Tysabri®) is the first monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS) but while treatment is highly efficient, it carries the risk of progressive multifocal leukoencephalopathy (PML). Based on reports of confirmed cases of PML, the risk of PML might increase beyond 24 months of treatment. Thus, attempts to stratify patients treated with natalizumab into those carrying higher or lower risk for developing PML are currently being undertaken. Among these strategies JC virus serology might potentially be the first tool available. As a large variety of methods have been published resulting in controversial results for JC virus seroprevalence, standardized testing will be mandatory when applying this method in clinical practice. In addition, risk management strategies for the seropositive majority of patients need to be redefined and optimized further.

Critical appraisal of the role of fingolimod in the treatment of multiple sclerosis

“…When looking at the efficacy of natalizumab and first-line DMDs across different clinical trials on clinical outcome measures such as the annualized relapse rate (ARR), the data available suggest superiority of natalizumab; this is supported by clinical experience (class IV evidence) 4. Therefore, restricted approval as a second-line treatment is not explained by inferiority compared with first-line DMDs or by study design of trials relevant for approval; it is explained mainly by the occurrence of cases of progressive multifocal leukoencephalopathy (PML) in around 1/1000 patients treated with natalizumab 12–15. The risk of this potentially lethal or highly disabling adverse event (AE) increases to up to 8.1/1000 patients (95% confidence interval: 5.4–11.6/1000 patients) among a subset of patients with prior immunosuppressant treatment who have been treated with natalizumab for more than 2 years, and who show evidence of JC virus exposure as assessed by JC virus serology 16…”