Monoclonal antibody therapy-associated neurological disorders

Several neurological disorders have been associated with the use of monoclonal antibodies (mAbs), especially those targeting tumor necrosis factor (TNF) and its receptors. These disorders include, among others, multiple sclerosis, optic neuritis, and various forms of peripheral demyelinating neuropathy. Progressive multifocal leukoencephalopathy, the natural course of which is lethal within months, has been mainly associated with the anti-alpha 4-integrin mAb natalizumab and, to a lesser extent, with rituximab, alemtuzumab and efalizumab. The prevalence of demyelinating disease induced by biological therapies, as reported in randomized controlled trials and postmarketing studies, has been estimated to range from 0.02-0.20%. Peripheral neuropathies can occur early or late after initiation of therapy. Short-term follow-up indicates relatively good outcomes, sometimes after mAb discontinuation alone, although corticosteroids or intravenous immunoglobulin may be necessary to reverse and stabilize the condition. Definitive cessation of the biological therapy should be discussed on a case-by-case basis. Prospective postmarketing studies in which the control group includes patients with rheumatic autoimmune diseases-most notably rheumatoid arthritis-treated with conventional therapies could help us to evaluate the real risks and outcomes in patients receiving mAbs who develop neurological diseases.