Biomarkers identification for PML monitoring, during Natalizumab (Tysabri®) treatment in Relapsing-Remitting Multiple Sclerosis.

Natalizumab (NTZ, Tysabri®; Biogen-Idec, Cambridge, MA, USA) is a humanized anti-α4 integrin monoclonal antibody, largely used in the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS). Although the drug has shown great efficacy in clinical trials (AFFIRM and SENTINEL) and in post-marketing observational studies (TYGRIS), by reducing clinical signs as disability status progression, brain lesions and annual relapse rate, there are numerous papers concerning the associated risk of progressive multifocal leukoencephalopathy (PML). PML is a brain infection caused by John Cunningham virus (JCV) and its incidence is related to intrinsic and extrinsic risk factors, such as long-term natalizumab therapy (more than 24 infusion doses), previous pharmacological immunosuppressive treatment and JVC antibody-positive status. The identification of risk factors provides an instrument to improve treatment decisions and to obtain an accurate benefit-risk evaluation. In order to evaluate the most appropriate natalizumab-MS therapy and to obtain minor incidence of PML, an accurate description of risk factors and a biological markers identification are needed. This article review aims to list some biomarkers that have been proposed to evaluate the safety of natalizumab therapy.