Demyelination as a complication of new immunomodulatory treatments.
OBJECTIVE
This review discusses demyelinating events of the nervous system that have been associated with new immunomodulatory treatments, in particular monoclonal antibodies (mAbs).


RESULTS
Natalizumab, a mAb targeting the alpha-4 integrins, which is efficient in relapsing-remitting multiple sclerosis, has been associated with progressive multifocal leukoencephalopathy (PML). We will review the putative mechanisms linking natalizumab with JC virus, the agent of PML. Efalizumab, a mAb targeting a member of the integrin family, CD11a, was approved for the treatment of psoriasis, but had to be withdrawn in 2009 because of the occurrence of three cases of PML. Rituximab, an anti-CD20 mAb, is used in different neoplastic and autoimmune diseases and may soon enter the pharmacopeia of multiple sclerosis. It has been suggested that rituximab is a risk factor for PML; however, evidence of such a link is unclear. Antitumor necrosis factor-alpha agents are used in several autoimmune diseases. Several cases of demyelinating events of the nervous system have been reported, prompting a heightened surveillance of treated patients. Recent data are reassuring, suggesting that the incidence of such events is relatively low.


CONCLUSIONS
Neurologists must become familiar with neurological complications of new immunomodulatory treatments, a field situated at the interface of neurology, immunology and infection.
Lysandropoulos
Andreas P
AP
Service of Neurology, Department of Clinical Neurosciences, Switzerland.
Du Pasquier
Renaud A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007049:Iatrogenic Disease / Q000517:prevention & control*; D007155:Immunologic Factors / Q000009:adverse effects*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000276:immunology / Q000503:physiopathology; D000069442:Natalizumab; D009420:Nervous System / Q000187:drug effects / Q000276:immunology / Q000503:physiopathology; D018570:Risk Assessment / Q000592:standards; D000069283:Rituximab; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069442:Natalizumab; D014409:Tumor Necrosis Factor-alpha; D000069283:Rituximab; C472181:efalizumab