Tumor necrosis factor (TNF) inhibition in the treatment of vasculitis

Tumor necrosis factor (TNF) is a major cytokine in the pathogenesis of inflammatory bowel disease (IBD), and TNF inhibition is a cornerstone of contemporary IBD therapy. However, paradoxical induction of IBD has recently been reported upon treatment of rheumatologic disorders with TNF inhibitors. In previous cases, induction of IBD was associated with one single drug and IBD was successfully managed by switching TNF inhibitors. We report the case of a patient with juvenile rheumatoid arthritis under long-term treatment with etanercept. After switching TNF inhibition to adalimumab, symptoms of Crohn's disease (CD) occurred and the diagnosis of CD was established by endoscopy. Further treatment with adalimumab and subsequently infliximab aggravated the abdominal symptoms, necessitating ileocecal resection, after which symptoms resolved for several months. Etanercept treatment due to recurrent rheumatologic symptoms was followed by recurrent CD symptoms and findings, which resolved upon discontinuation of etanercept. This case suggests that induction, aggravation and recurrence of IBD can be rare class effects of TNF inhibition.

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Treatment with Tumor Necrosis Factor Inhibitors in Axial Spondyloarthritis: Comparison Between Private Rheumatology Practices and Academic Centers in a Large Observational Cohort

The Journal of Rheumatology ◽

10.3899/jrheum.140229 ◽

2014 ◽

Vol 42 (1) ◽

pp. 101-105 ◽

Cited By ~ 5

Author(s):

Adrian Ciurea ◽

Ulrich Weber ◽

Daniel Stekhoven ◽

Almut Scherer ◽

Giorgio Tamborrini ◽

...

Keyword(s):

Ankylosing Spondylitis ◽

Tumor Necrosis Factor ◽

Disease Activity ◽

Tumor Necrosis ◽

Axial Spondyloarthritis ◽

Tnf Inhibitors ◽

University Hospitals ◽

Private Practices ◽

Tnf Inhibition ◽

Necrosis Factor

Objective.To evaluate the initiation of and response to tumor necrosis factor (TNF) inhibitors for axial spondyloarthritis (axSpA) in private rheumatology practices versus academic centers.Methods.We compared newly initiated TNF inhibition for axSpA in 363 patients enrolled in private practices with 100 patients recruited in 6 university hospitals within the Swiss Clinical Quality Management (SCQM) cohort.Results.All patients had been treated with ≥ 1 nonsteroidal antiinflammatory drug and > 70% of patients had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 before anti-TNF agent initiation. The proportion of patients with nonradiographic axSpA (nr-axSpA) treated with TNF inhibitors was higher in hospitals versus private practices (30.4% vs 18.7%, p = 0.02). The burden of disease as assessed by patient-reported outcomes at baseline was slightly higher in the hospital setting. Mean levels (± SD) of the Ankylosing Spondylitis Disease Activity Score were, however, virtually identical in private practices and academic centers (3.4 ± 1.0 vs 3.4 ± 0.9, p = 0.68). An Assessment of SpondyloArthritis international Society (ASAS40) response at 1 year was reached for ankylosing spondylitis in 51.7% in private practices and 52.9% in university hospitals (p = 1.0) and for nr-axSpA in 27.5% versus 25.0%, respectively (p = 1.0).Conclusion.With the exception of a lower proportion of patients with nr-axSpA newly treated with anti-TNF agents in private practices in comparison to academic centers, adherence to ASAS treatment recommendations for TNF inhibition was equally high, and similar response rates to TNF blockers were achieved in both clinical settings.

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Blockade of tumor necrosis factor in collagen-induced arthritis reveals a novel immunoregulatory pathway for Th1 and Th17 cells

Journal of Experimental Medicine ◽

10.1084/jem.20072707 ◽

2008 ◽

Vol 205 (11) ◽

pp. 2491-2497 ◽

Cited By ~ 142

Author(s):

Clare A. Notley ◽

Julia J. Inglis ◽

Saba Alzabin ◽

Fiona E. McCann ◽

Kay E. McNamee ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Th17 Cell ◽

Th17 Cells ◽

Tumor Necrosis ◽

Collagen Induced Arthritis ◽

Fc Fusion Protein ◽

The Impact ◽

Tnf Inhibition ◽

Necrosis Factor

IL-17 is implicated in the pathogenesis of rheumatoid arthritis (RA) and has previously been shown to be induced by tumor necrosis factor (TNF) in vitro. The aim of this study was to assess the impact of TNF inhibition on IL-17 production in collagen-induced arthritis, a model of RA. TNF blockade using TNFR-Fc fusion protein or anti-TNF monoclonal antibody reduced arthritis severity but, unexpectedly, expanded populations of Th1 and Th17 cells, which were shown by adoptive transfer to be pathogenic. Th1 and Th17 cell populations were also expanded in collagen-immunized TNFR p55−/− but not p75−/− mice. The expression of IL-12/IL-23 p40 was up-regulated in lymph nodes (LN) from p55−/− mice, and the expansion of Th1/Th17 cells was abrogated by blockade of p40. Treatment of macrophages with rTNF also inhibited p40 production in vitro. These findings indicate that at least one of the ways in which TNF regulates Th1/Th17 responses in arthritis is by down-regulating the expression of p40. Finally, although TNF blockade increased numbers of Th1 and Th17 cells in LN, it inhibited their accumulation in the joint, thereby providing an explanation for the paradox that anti-TNF therapy ameliorates arthritis despite increasing numbers of pathogenic T cells.

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Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1998.275.5.e757 ◽

1998 ◽

Vol 275 (5) ◽

pp. E757-E762 ◽

Cited By ~ 11

Author(s):

Davide Agnello ◽

Riccardo Bertini ◽

Silvano Sacco ◽

Cristina Meazza ◽

Pia Villa ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Inhibitory Effect ◽

Direct Inhibitory Effect ◽

Anti Inflammatory ◽

Camp Levels ◽

Tnf Inhibition ◽

Pituitary Adrenal Axis ◽

Necrosis Factor

Urocortin (UCN) is a neuropeptide homologous with corticotropin-releasing factor (CRF), which has anti-inflammatory activities not all mediated by corticosteroids. In mice, UCN (1 μg/mouse sc) significantly reduced lipopolysaccharide (LPS)-induced serum tumor necrosis factor (TNF) and interleukin (IL)-1β levels in vivo but did not affect serum IL-6. These effects were paralleled by a rise in corticosterone (CS) levels. Blockade of the CS increase by cyanoketone did not prevent TNF inhibition by UCN, suggesting the neuropeptide has anti-inflammatory mechanisms independent of the hypothalamus-pituitary-adrenal axis. In fact UCN had a direct inhibitory effect on LPS-induced TNF in rat Kupffer cells at concentrations between 10−10 and 10−16 M, and this effect was related to increased cAMP levels. However, the in vivo inhibition of LPS-induced IL-1β by UCN was reversed by cyanoketone, indicating that the increase of endogenous glucocorticoids might be more important in IL-1β inhibition than in TNF inhibition by UCN.

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