Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey

Séror, Raphaèle; Richez, Christophe; Sordet, Christelle; Rist, Stéphanie; Gossec, Laure; Direz, Guillaume; Houvenagel, É.; Berthelot, Jean‐Marie; Pagnoux, Christian; Dernis, Emmanuelle; Melac-Ducamp, Sylvie; Bouvard, Béatrice; Asquier, C.; Martin, Antoine; Puéchal, Xavier; Mariette, Xavier

doi:10.1093/rheumatology/kes375

Cited by 126 publications

(102 citation statements)

References 12 publications

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“…Although our data support the previous work implicating TNF-a as a key cytokine that can dramatically influence oligodendrocyte biology (Fig. 4), we know that anti-TNF-a therapies are not a clinically relevant reality in MS because they can exacerbate the disease and even initiate MS-like symptoms and diagnoses in other patient populations (28)(29)(30). Although the mechanisms remain unclear, TNF-a has two known receptors (TNFR1 and TNFR2) that have pleiotropic effects in the context of neurodegenerative diseases (31)(32)(33)(34).…”

Section: Discussionsupporting

confidence: 86%

Direct and Indirect Effects of Immune and Central Nervous System–Resident Cells on Human Oligodendrocyte Progenitor Cell Differentiation

Moore

Cui

Warsi

et al. 2015

The Journal of Immunology

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In multiple sclerosis, successful remyelination within the injured CNS is largely dependent on the survival and differentiation of oligodendrocyte progenitor cells. During inflammatory injury, oligodendrocytes and oligodendrocyte progenitor cells within lesion sites are exposed to secreted products derived from both infiltrating immune cell subsets and CNS-resident cells. Such products may be considered either proinflammatory or anti-inflammatory and have the potential to contribute to both injury and repair processes. Within the CNS, astrocytes also contribute significantly to oligodendrocyte biology during development and following inflammatory injury. The overall objective of the current study was to determine how functionally distinct proinflammatory and anti-inflammatory human immune cell subsets, implicated in multiple sclerosis, can directly and/or indirectly (via astrocytes) impact human oligodendrocyte progenitor cell survival and differentiation. Proinflammatory T cell (Th1/Th17) and M1-polarized myeloid cell supernatants had a direct cytotoxic effect on human A2B5+ neural progenitors, resulting in decreased O4+ and GalC+ oligodendrocyte lineage cells. Astrocyte-conditioned media collected from astrocytes pre-exposed to the same proinflammatory supernatants also resulted in decreased oligodendrocyte progenitor cell differentiation without an apparent increase in cell death and was mediated through astrocyte-derived CXCL10, yet this decrease in differentiation was not observed in the more differentiated oligodendrocytes. Th2 and M2 macrophage or microglia supernatants had neither a direct nor an indirect impact on oligodendrocyte progenitor cell differentiation. We conclude that proinflammatory immune cell responses can directly and indirectly (through astrocytes) impact the fate of immature oligodendrocyte-lineage cells, with oligodendrocyte progenitor cells more vulnerable to injury compared with mature oligodendrocytes.

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Section: Discussionsupporting

confidence: 86%

Direct and Indirect Effects of Immune and Central Nervous System–Resident Cells on Human Oligodendrocyte Progenitor Cell Differentiation

Moore

Cui

Warsi

et al. 2015

The Journal of Immunology

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“…Our cases, as well as others [18], clearly support discontinuation of any type of anti-TNFα treatment. If the patient does not fulfill the criteria for MS (clinically isolated symptom with atypical demyelination), we believe that MS treatment should be withheld and that clinical/MRI follow-up at 6-month or 1-year intervals may suffice.…”

Section: Discussionsupporting

confidence: 87%

“…Despite initial experimental data supporting a potentially therapeutic effect of anti-TNFα treatment on autoimmune demyelination [15], clinical data revealed that anti-TNFα drugs can potentially exacerbate a latent MS or induce atypical CNS demyelination [2,14,16]. Specifically in AS, single cases [7,17] as well as recent large cohorts [18] report sequential development of typical MS or CNS demyelination (such as optic neuritis or myelitis) after anti-TNFα treatment. In our cases, similar treatment resulted in either exacerbation of an already diagnosed MS (case 1), or in de novo development of neurological symptoms and brain MRI lesions in cases 3-5; the presence of MS in case 2 discouraged the treating rheumatologist from prescribing an anti-TNFα regimen.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of Multiple Sclerosis and Ankylosing Spondylitis: Report of Two Cases

Lourbopoulos¹,

Ioannidis²,

Boura³

et al. 2013

Eur Neurol

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Background: Multiple sclerosis (MS) only rarely coexists with ankylosing spondylitis (AS). The optimal management of these patients represents a major challenge. Methods: In the present study, we report 2 cases of AS with definite MS comorbidity. One of the AS-MS cases had received anti-TNFα treatment, which was discontinued due to exacerbation of the MS. In addition, we discuss 3 more AS cases with neurological symptoms and atypical white matter demyelinating MRI lesions after anti-TNFα treatment. Discussion: Given the fact that anti-TNFα drugs can potentially exacerbate a latent MS or induce atypical demyelination in the central nervous system, they should be discouraged or discontinued in relevant cases. The remaining effective therapeutic options for MS are either contradictory for AS (interferon-β), have no definite data regarding their safety/efficacy in AS (glatiramer acetate, azathioprine, natalizumab, fingolimod), or their efficacy in MS-AS is associated with increased treatment risks (rituximab). Any of these proposed treatments may require active patient's informed consent.

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“…Demyelinating CNS and PNS disorders, following treatment with anti-TNF agents, have been described in many clinical studies and case series [190][191][192][193][194][195]. However, contradictory reports do exist; a prospective study in patients who had undergone neurological examination and neuroimaging studies before anti-TNF treatment initiation showed that the frequency of demyelination due to anti-TNF treatment is rather low [196].…”

Section: Cns and Pns Demyelination Caused By Anti-tnf Agentsmentioning

confidence: 99%

Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity

et al. 2016

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Neurological involvement is relatively common in the majority of systemic autoimmune diseases and may lead to severe morbidity and mortality, if not promptly treated. Treatment options vary greatly, depending on the underlying systemic pathophysiology and the associated neurological symptoms. Selecting the appropriate therapeutic scheme is further complicated by the lack of definite therapeutic guidelines, the necessity to differentiate primary neurological syndromes from those related to the underlying systemic disease, and to sort out adverse neurological manifestations caused by immunosuppressants or the biological agents used to treat the primary disease. Immunotherapy is a sine qua non for treating most, if not all, neurological conditions presenting in the context of systemic autoimmunity. Specific agents include classical immune modulators such as corticosteroids, cyclophosphamide, intravenous immunoglobulin, and plasma exchange, as well as numerous biological therapies, for example antitumor necrosis factor agents and monoclonal antibodies that target various immune pathways such as B cells, cytokines, and co-stimulatory molecules. However, experience regarding the use of these agents in neurological complications of systemic diseases is mainly empirical or based on small uncontrolled studies and case series. The aim of this review is to present the state-of-the-art therapies applied in various neurological manifestations encountered in the context of systemic autoimmune diseases; evaluate all treatment options on the basis of existing guidelines; and compliment these data with our personal experience derived from a large number of patients.

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Pattern of demyelination occurring during anti-TNF-α therapy: a French national survey

Cited by 126 publications

References 12 publications

Direct and Indirect Effects of Immune and Central Nervous System–Resident Cells on Human Oligodendrocyte Progenitor Cell Differentiation

Direct and Indirect Effects of Immune and Central Nervous System–Resident Cells on Human Oligodendrocyte Progenitor Cell Differentiation

Coexistence of Multiple Sclerosis and Ankylosing Spondylitis: Report of Two Cases

Immunotherapies for Neurological Manifestations in the Context of Systemic Autoimmunity

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