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Chronic Inflammatory Demyelinating Polyneuropathy Biological Agents for Chronic Inflammatory Demyelinating Polyradiculoneuropathy Joerg-Patrick Stübgen, MB ChB, MD Professor of Clinical Neurology/Attending Neurologist, Department of Neurology and Neuroscience, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York, US Abstract Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a term for a group of acquired, immune-mediated inflammatory demyelinating disorders of the peripheral nervous system. Most patients with CIDP respond to ‘first-line’ therapy with intravenous immunoglobulin (IVIG), plasmapheresis, and/or corticosteroids. ‘Conventional’ immunosuppressive drugs are of no proven benefit. Biological agents directed at key aspects of the CIDP immunopathogenic pathway have gained increasing attention due to the unpredictable efficacy and overall health risks of non-targeted immunosuppressive drugs. Presently, there exists insufficient clinical experience with biological therapy to allow specific treatment recommendations for CIDP. The challenge remains to identify drug-naïve or treatment-resistant CIDP patients who will most likely respond to targeted immunotherapy. Keywords Biological therapy, CIDP, monoclonal antibodies, interferon, tumor necrosis factor alpha Disclosure: The author has no conflicts of interest to declare. Received: March 18, 2013 Accepted: April 22, 2013 Citation: US Neurology, 2014;10(1):38-43 Correspondence: Joerg-Patrick Stübgen, MB ChB, MD, Department of Neurology and Neuroscience, Weill Cornell Medical College/New York Presbyterian Hospital, 525 East 68th Street, New York NY 10065-4885, US. E: pstuebge@med.cornell.edu Chronic inflammatory demyelinating polyneuropathy (CIDP) denotes a spectrum of acquired, chronically progressive, or recurrent, immune- mediated disorders of the peripheral nervous system with variable pathology and pathogenesis. 1 The estimated prevalence may be up to nine per 100,000 population. 2,3 A universally accepted definition of disease does not exist. A variety of clinical and investigational criteria have been proposed and applied in attempts to include the various presentations of CIDP. 4,5 Perhaps the future development of biological markers will help reliably identify patients with CIDP. 4 The pathogenesis of CIDP is not fully understood. 1,6,7 Cell-mediated and/or humoral immune mechanisms are involved in an attack against unidentified target antigen(s) of the myelin sheath and/or Schwann cells, at times leading also to secondary axonal injury. Randomised controlled trials (class I evidence) showed that most (60–80 %) patients respond at least to a degree to treatment with intravenous immunoglobulin (IVIG), 8–11 plasmapheresis, 12,13 or corticosteroids. 14 Yet, there exists insufficient (class IV) evidence (from open label case series, randomized, and quasi-randomized trials) to assess the benefits of conventional immunosuppressive agents (azathioprine, cyclosporine, methotrexate, cyclophosphamide, or mycophenolate mofetil) in patients with CIDP. 15,16 Most patients require long-term maintenance treatment. 17,18 Due to the unpredictable efficacy, financial burden, and/or toxicity of 38 ‘broad-spectrum’ immunomodulatory/-suppressive drugs, a need exists to develop effective and safe therapeutic strategies. 19,20 Research is hindered by the current lack of consensus on appropriate outcome measures and definition of treatment failure, as well as the tendency to study potentially effective therapy exclusively on refractive CIDP patients. 21,22 In order to realize the full potential of any new drug/agent, it may be advisable to identify and exclude from future drug trials any patients with predictably unresponsive (chronically stable and inactive) disease. 20 The future development and application of biomarkers could assist in the selection of effective therapy at initiation and long-term. 23 This review offers an updated summary and analysis of the genetically engineered, biological therapeutic agents considered potentially useful in patients with CIDP. Specific recommendations on management strategies are not proposed, as reviews on this subject have been published. 24–28 Biological therapeutics may rarely induce dysimmune inflammatory neuropathies (discussed elsewhere). 29 T-lymphocytes Activated T-lymphocytes invade peripheral nerve and partake in the pathogenesis of CIDP. 6,7,30 Natalizumab Natalizumab (Tysabri®) is a monoclonal antibody (mAb) targeted at the α4 subunit of α4β1 (VLA4) and α4β7 integrins that are expressed on © TOU C H ME D ICA L ME D IA 2014