Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease

Levin, Alon D.; Wildenberg, Manon E.; Brink, Gijs R. van den

doi:10.1093/ecco-jcc/jjw053

Cited by 246 publications

(180 citation statements)

References 67 publications

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“…Corticosteroids are known to induce apoptosis in lymphocytes but not neutrophils [14] and to induce demargination of neutrophils from the endovascular lining. Similarly, infliximab functions by inducing apoptosis of activated T-lymphocytes through transmembrane TNFα, in addition to inhibiting soluble TNFα [15]. …”

Section: Introductionmentioning

confidence: 99%

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Bergqvist

Hertervig

Gedeon

et al. 2017

Cancer Immunol Immunother

196

156

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Immune checkpoint inhibitors (ICPI), such as ipilimumab [anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody] and nivolumab or pembrolizumab [anti-programmed cell death protein-1 (PD-1) antibodies], improve survival in several cancer types. Since inhibition of CTLA-4 or PD-1 leads to non-selective activation of the immune system, immune-related adverse events (irAEs) are frequent. Enterocolitis is a common irAE, currently managed with corticosteroids and, if necessary, anti-tumor necrosis factor-α therapy. Such a regimen carries a risk of serious side-effects including infections, and may potentially imply impaired antitumor effects. Vedolizumab is an anti-integrin α4β7 antibody with gut-specific immunosuppressive effects, approved for Crohn’s disease and ulcerative colitis. We report a case series of seven patients with metastatic melanoma or lung cancer, treated with vedolizumab off-label for ipilimumab- or nivolumab-induced enterocolitis, from June 2014 through October 2016. Clinical, laboratory, endoscopic, and histologic data were analyzed. Patients initially received corticosteroids but were steroid-dependent and/or partially refractory. One patient was administered infliximab but was refractory. The median time from onset of enterocolitis to start of vedolizumab therapy was 79 days. Following vedolizumab therapy, all patients but one experienced steroid-free enterocolitis remission, with normalized fecal calprotectin. This was achieved after a median of 56 days from vedolizumab start, without any vedolizumab-related side-effects noted. The patient in whom vedolizumab was not successful, due to active ulcerative colitis, received vedolizumab prophylactically. This is the first case series to suggest that vedolizumab is an effective and well-tolerated therapeutic for steroid-dependent or partially refractory ICPI-induced enterocolitis. A larger prospective study to evaluate vedolizumab in this indication is warranted.

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Section: Introductionmentioning

confidence: 99%

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Bergqvist

Hertervig

Gedeon

et al. 2017

Cancer Immunol Immunother

196

156

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“…45,46 By contrast, Wojtal et al 47 has suggested that the Fc receptor CD64 could be connected to reduced responsiveness to IFX in IBD. The study detected increased expression of interferon γ (IFN-γ) in the inflamed colonic tissue from nonresponders, which could lead to increased transcription of the CD64 gene.…”

Section: The Role Of Fc Receptorsmentioning

confidence: 98%

Update on the mechanisms of action of anti‑TNF-α antibodies and their clinical implications in inflammatory bowel disease

Eder¹,

Linke²,

Witowski³

2016

Polish Archives of Internal Medicine

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“…These substances induce apoptosis of CD4 + -T-cells and macrophages and influence the cytokine milieu by binding to soluble and membrane-bound TNF [42]. Due to the lack of an Fc region in certolizumab, some effects are only observed with adalimumab and infliximab [43]. …”

Section: Approved Substances – State Of the Artmentioning

confidence: 99%

Treatment Perspectives in Crohn’s Disease

Vetter¹

2018

Digestion

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Background: Crohn’s disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained. Summary: Clinically established therapies in active CD comprise corticosteroids and immunosuppressants such as azathioprine. After the introduction of anti-TNFα (Tumor necrosis factor alpha) antibodies, other biologicals (e.g., vedolizumab and ustekinumab) have also been approved. New drugs in the pipeline like filgotinib, upadacitinib, risankizumab or rifaximin could improve the therapy of CD in the near future. Thus, an individualized therapy management, based on optimal selection of therapeutic agents will become more important. Additionally, the local application of mesenchymal stem cells might be helpful in the management of fistulas. Key Messages: The targeted biological therapeutic agents (anti-TNFα antibodies, vedolizumab, ustekinumab) are well established for therapy in CD. There are several new substances in the pipeline with promising results in phase II trials (filgotinib, rifaximin, risankizumab, upadacitinib). The upcoming extension of the therapeutic arsenal will require methods for an optimized selection of substances, thus enabling a more individualized therapy.

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Mechanism of Action of Anti-TNF Therapy in Inflammatory Bowel Disease

Cited by 246 publications

References 67 publications

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Update on the mechanisms of action of anti‑TNF-α antibodies and their clinical implications in inflammatory bowel disease

Treatment Perspectives in Crohn’s Disease

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