An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab

Wyant, Tim; Fedyk, Eric R.; Abhyankar, Brihad

doi:10.1093/ecco-jcc/jjw092

Cited by 204 publications

(167 citation statements)

References 79 publications

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“…α4β7 integrin is expressed primarily on a subset of CD4 + T cells and mediates homing of these cells specifically to the gut [18, 19]. The counter-receptor of α4β7, mucosal addressin cellular adhesion molecule 1 (MAdCAM-1), is expressed selectively on venule endothelial cells of the gut but not in other organs [18, 20]. Blocking of α4β7 integrin thus results in a gut-specific immunosuppression, while the immunity in extraintestinal tissues remains intact [20].…”

Section: Introductionmentioning

confidence: 99%

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Bergqvist

Hertervig

Gedeon

et al. 2017

Cancer Immunol Immunother

200

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

200

156

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“…By binding to the α4β7 integrin subunit and blocking its interaction with mucosal addressin cell adhesion molecule-1, vedolizumab inhibits leukocyte adhesion and migration 4, 5. Because IBD is largely driven by lymphocyte trafficking to sites of inflammation, and mucosal addressin cell adhesion molecule-1 is specifically expressed by blood vessels in the gastrointestinal tract, vedolizumab is unique in its gut selectivity and more targeted immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Intractable pyoderma gangrenosum in a Crohn's disease patient on vedolizumab

Yeh

Tsiaras

2017

JAAD Case Reports

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“…Due to the mode of action as a selective integrin inhibitor in the gut, there is concern that anastomotic healing after bowel resection may be impaired [15]. …”

Section: Perioperative Handling Of Medicationmentioning

confidence: 99%

Impact of Modern Drug Therapy on Surgery: Crohn's Disease

Kienle¹

2018

Visc Med

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Background: A significant number of patients with Crohn's disease needs to undergo surgery, and many of these patients are under modern drug treatment. These drugs may influence the rate of perioperative complications. This may have an impact on the chosen surgical strategy. Methods: This review considers clinical studies and guidelines on the effect of modern drug treatment on surgical complication rates and surgical strategy in patients with Crohn's disease. Results: Steroids above a certain dose significantly influence perioperative complications and should therefore be tapered down before performing elective surgery. Anti-TNF-alpha drugs are associated with perioperative complications, and therefore a safe interval between drug intake and surgery should be adhered to. The data on newer biologicals is scarce and conflicting; thus, it seems prudent to wait at least for one dosing interval before operating. In the emergency setting, patients undergoing bowel resection while on the above medications without an adequate interval to the last medication dose should generally get a resectional or diverting stoma. Conclusion: Modern drug treatment influences the surgical strategy in patients with Crohn's disease.

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An Overview of the Mechanism of Action of the Monoclonal Antibody Vedolizumab

Cited by 204 publications

References 79 publications

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis

Intractable pyoderma gangrenosum in a Crohn's disease patient on vedolizumab

Impact of Modern Drug Therapy on Surgery: Crohn's Disease

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