The Risk of Progressive Multifocal Leukoencephalopathy Under Biological Agents Used in the Treatment of Chronic Inflammatory Diseases
Eric Toussirot and Matthieu Bereau
Affiliation: University Hospital of Besançon, Clinical Investigation Center for Biotherapy INSERM CIC-1431, Place St Jacques, 25000 Besançon, France.
Biological agents such as monoclonal antibodies and soluble cytokine receptors have taken on an expanding
role in the treatment of chronic immune mediated diseases. Progressive multifocal leukoencephalopathy (PML) is a rare
central neurological disease caused by JC virus infection that has been described in the setting of conditions with severe
impairment of immune surveillance, such as haematological malignancies, stem cell or solid organ transplantation and
AIDS. This serious demyelinating disease has recently been described in patients receiving monoclonal antibodies for
chronic inflammatory diseases such as multiple sclerosis, Crohn’s disease, rheumatoid arthritis, systemic lupus
erythematosus or psoriasis. We review here the disease of PML, the different biological agents used in chronic
inflammatory diseases that are associated with an increased risk of PML (natalizumab, rituximab, efalizumab and
alemtuzumab), and the potential mechanisms that may explain the development of PML. Based on current knowledge of
the biology of the JC virus and on the mechanisms of action of these biological agents, we discuss currently available
tools that may be helpful in evaluating the risk of PML in this patient population.
Keywords: JC virus, progressive multifocal leukoencephalopathy, monoclonal antibodies, natalizumab, rituximab.
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