Demyelinating Neuropathies as a Consequence of TNF-a-Blocker Therapy
Demyelinating Neuropathies as a Consequence of TNF-a-Blocker Therapy
Abstract & commentary
By Norman Latov, MD,PhD, Professor of Neurology and Neuroscience, and Director of the Peripheral Neuropathy Center, Weill Medical College of Cornell University. Dr. Latov served as consultant to Quest Diagnostics, Talecris Biotheapeutics, CSL Behring Biotherapies, Baxter Bioscience, and Octapharma AG , and owns stock in Therapath LLC.
Synopsis: Five cases of demyelinating neuropathy are reported as a consequence of treatment with anti-tumor necrosis factor drugs for auto-immune disorders.
Source: Lozeron P, Denier C, Lacroix C, et al. Long term course of demyelinating neuropathies occurring during tumor necrosis factor-a-blocker therapy. Arch Neurol 2009; 66:490-497.
Anti-tumor necrosis factor (TNF-a) drugs are immunosuppressive agents that prevent the pro-inflammatory effects of the cytokine TNF-a. They include etanercept (Enbrel), a TNF-a-binding fusion protein of the TNF-a receptor linked to the Fc portion of IgG, infliximab (Remicade), a mouse-human chimeric monoclonal antibody that blocks the binding of TNF to its receptor, and the fully human monoclonal anti-TNF antibodies adalimumab (Humera) and golimumab (Simponi). Anti-TNF-a drugs are FDA-approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, sarcoidosis, and Crohn's disease.
The authors present five cases of chronic demyelinating neuropathies that developed within several months after beginning anti-TNF-a therapy. One patient presented with the Lewis-Sumner syndrome, one with multifocal motor neuropathy, two with multifocal sensorimotor neuropathies, and one with multifocal sensory neuropathy. Electrophysiologic or nerve biopsy studies revealed demyelinating features in all five patients, although only one fulfilled the American Academy of Neurology (AAN) criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). Underlying diseases included rheumatoid arthritis, Crohn's disease, psoriasis or psoriatic arthritis, and anti-TNF-a. Drugs included infliximab, etanercept, and adalimumab.
Treatment with anti-TNF agents was discontinued in three patients. One of the three improved after a course of therapy with intravenous immunoglobulin (IVIG), but then relapsed and required chronic treatment. In a second, deficits remained for five months and then dramatically improved after IVIG treatment. A third improved after therapy with plasmapheresis and IVIG. Two of the patients remained on anti-TNF medications; one on reduced dose, and the other concomitantly treated with IVIG and prednisone, with clinical stabilization in both.
Commentary
The neuropathy in all five patients was thought to be autoimmune because they had features of demyelination as occurs in CIDP, and they responded to immune therapy. Although anti-TNF-a agents are used to treat autoimmune diseases, and have been reported to be beneficial in some patients with CIDP,1 their use was reported to be associated with exacerbations of multiple sclerosis, or with development of new onset vasculitis,2 so that they can also exacerbate or trigger autoimmune disease. Other anti-inflammatory agents have also been reported to occasionally exacerbate autoimmune disease, as is the case for corticosteroids in multifocal motor neuropathy, emphasizing the complexity of the immune system and diversity of autoimmune diseases.
Acquired demyelinating neuropathies are considered to be autoimmune until proven otherwise, so that the diagnosis and treatment of these patients rests, in part, on demonstrating the presence of demyelination. There is no general agreement, however, as to the number and type of demyelinating abnormalities required for diagnosis, with only one of the five patients fulfilling the AAN criteria for demyelinating neuropathy, so that a nerve biopsy with teased fiber analysis was required to prove the diagnosis in some patients. Not all autoimmune neuropathies are demyelinating, however, raising the question of whether patient that develops a axonal neuropathy while on TNF-a antagonists should be similarly treated.3
Unlike other drug-induced neuropathies that result from direct toxicity, management of autoimmune neuropathies such as CIDP, once triggered, may require chronic immune therapy beyond discontinuation of the offending medication.
References
1. Chin RL, Sherman WH, Sander HW, et al. Etanercept (Enbrel) therapy for chronic inflammatory demyelinating polyneuropathy. J Neurol Sci 2003;210:19-21.
2. Saint Marcoux B, De Bandt M. Vasculitides induced by TNF-alpha antagonists: A study in 29 patients in France. Joint Bone Spine 2006;73:719-723.
3. Latov N, Gorson K, Brannagan TH, et al. Diagnosis and treatment of chronic immune mediated neuropathies. Clin Neuromusc Dis 2006;7:141-157.
Five cases of demyelinating neuropathy are reported as a consequence of treatment with anti-tumor necrosis factor drugs for auto-immune disorders.Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.