Inflammatory demyelinating events following treatment with anti-tumor necrosis factor

doi:10.1016/j.cyto.2008.11.002

Cytokine

Volume 45, Issue 2, February 2009, Pages 55-57

https://doi.org/10.1016/j.cyto.2008.11.002 Get rights and content

Abstract

Background: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine involved in certain inflammatory diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn’s disease. The anti-TNF-α treatments used for RA may be associated with inflammatory demyelinating events affecting the central nervous system and may possibly aggravate known MS. Objective: We report here three new cases of inflammatory demyelinating events of the central nervous system following treatment with anti-TNF-α. Results: The neurological symptoms appeared on average 5 months after initiation of the treatment. For all patients, the inflammatory process was confirmed by brain magnetic resonance imaging. The symptoms totally or partially regressed as soon as anti-TNF-α treatment was stopped except for one patient who developed clinically defined MS. Conclusions: Inflammatory demyelination of the central nervous system may be associated with the use of anti-TNF-α. Patients with rheumatoid arthritis treated with these treatments should benefit from a follow-up which includes brain MRI.

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Tumor necrosis factor receptor 2 activation elicits sex-specific effects on cortical myelin proteins and functional recovery in a model of multiple sclerosis
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Multiple sclerosis (MS), a demyelinating autoimmune disease of the central nervous system (CNS), predominately affects females compared to males. Tumor necrosis factor (TNF), a pro-inflammatory cytokine, signaling through TNF receptor 1 contributes to inflammatory disease pathogenesis. In contrast, TNF receptor 2 signaling is neuroprotective. Current anti-TNF MS therapies are shown to be detrimental to patients due to pleiotropic effects on both pro- and anti-inflammatory functions. Using a non-pertussis toxin (nPTX) experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice, we systemically administered a TNFR2 agonist (p53-sc-mTNF_R2) to investigate behavioral and pathophysiological changes in both female and male mice. Our data shows that TNFR2 activation alleviates motor and sensory symptoms in females. However, in males, the agonist only alleviates sensory symptoms and not motor. nPTX EAE induction in TNFR2 global knockout mice caused exacerbated motor symptoms in females along with an earlier day of onset, but not in males. Our data demonstrates that TNFR2 agonist efficacy is sex-specific for alleviation of motor symptoms, however, it effectively reduces mechanical hypersensitivity in both females and males. Altogether, these data support the therapeutic promise TNFR2 agonism holds as an MS therapeutic and, more broadly, to treat central neuropathic pain.
NMOSD with anti-MOG antibodies following anti-TNFα therapy: A case report
2018, Multiple Sclerosis and Related Disorders
Tumor necrosis factor α (TNFα) inhibitors are highly effective and a therapeutic choice for several inflammatory diseases. Their broad and long-term use is associated with a growing number of paradoxical autoimmune events including demyelinating lesions of the central nervous system (CNS). We report and discuss a case of neuromyelitis optica spectrum disorder (NMOSD) with positive myelin oligodendrocyte glycoprotein antibodies (MOG-IgG1) following anti-TNFα therapy for a pustular psoriasis.
Central nervous system involvement in rheumatoid arthritis patients and the potential implications of using biological agents
2018, Best Practice and Research: Clinical Rheumatology
Central nervous system (CNS) involvement is quite unusual in patients with rheumatoid arthritis (RA), although cerebral vasculitis, rheumatoid nodules and meningitis have all been reported, and patients with RA may also have CNS comorbidities such as stroke and neuro-degenerative and demyelinating syndromes. It has been found that biological drugs, especially anti-tumour necrosis factor-alpha (anti-TNF-α) drugs, slightly increase the risk of developing demyelinating diseases, and they are consequently discouraged in patients with multiple sclerosis and related disorders. Furthermore, the risk of opportunistic CNS infections is increased in immunosuppressed patients.
To review the current literature concerning CNS involvement in patients with RA (including RA-related forms and comorbidities) and the incidence of new-onset CNS diseases in patients with RA undergoing biological treatment (anti-TNF or non-anti-TNF drugs), the Medline database was searched using the key words ‘rheumatoid arthritis’, ‘central nervous system’, ‘anti-TNF’, ‘abatacept’, ‘tocilizumab’, ‘rituximab’ and ‘anakinra’. Abstracts not in English were excluded.
We selected 76 articles published between 1989 and 2017, which were divided into four groups on the basis of whether CNS involvement was RA-related or not and according to the type of biological agent used (TNF inhibitors or other agents). The RA-related diseases included aseptic meningitis, vasculitis and cerebral rheumatoid nodules, which benefit from immunosuppressive treatments. CNS comorbidities included stroke, seizures, dementia and neuropsychiatric disorders, which have been frequently described in biological agent-naïve patients with RA, and other rarely reported neurological diseases, such as extra-pyramidal syndromes and demyelinating disorders. CNS comorbidities are relatively frequent among patients with RA and may be related to systemic inflammation or concomitant medications. The use of anti-TNF drugs is associated with the risk of developing demyelinating diseases, and CNS infections have been described in patients treated with anti-TNF and non-anti-TNF agents. Non-anti-TNF drugs may be preferred in the case of demyelinating diseases, cerebral vasculitis or neurolupus.
Patients with RA may suffer from CNS involvement as a manifestation of RA or as a comorbidity. The treatment of such medical conditions should be guided on the basis of their etiopathogenesis: steroids and immunosuppressants are useful in the case of RA-related CNS diseases but are often detrimental in other situations. Similarly, the choice of biological agents in patients with RA with CNS complications should be guided by a correct diagnosis in order to prevent further complications.
Autoimmune neuropathies associated to rheumatic diseases
2017, Autoimmunity Reviews
Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.
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Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology
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Review ArticleInflammatory demyelinating events following treatment with anti-tumor necrosis factor

Abstract

J Neuroimmunol

Gastroenterology

J Fr Ophtalmol

J AAPOS

Gastroenterology

Res Immunol

Clin Immunol

J Neurol Sci

Rev Neurol (Paris)

Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritis

Arthritis Rheum

Onset of multiple sclerosis associated with anti-TNF therapy

Neurology

Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis

Brain

Review Article
Inflammatory demyelinating events following treatment with anti-tumor necrosis factor