Postoperative complications of pediatric patients with inflammatory bowel disease treated with vedolizumab

Zimmerman, Lori A.; Zalieckas, Jill M.; Shamberger, Robert C.; Bousvaros, Athos

doi:10.1016/j.jpedsurg.2017.12.001

Cited by 24 publications

(11 citation statements)

References 12 publications

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“…Finally, these aspects culminate in the question on the translational relevance of our findings in the context of IBD therapy with the anti-α4β7 integrin antibody vedolizumab. While the impact of vedolizumab on postoperative course and complications is still controversially discussed,45 46 several reports indicate an increased rate of postoperative infectious surgical site complications in vedolizumab-treated patients undergoing abdominal operation 47–50. Although our punch biopsy wound healing model obviously differs from surgical wound healing in several aspects, our data suggest that such infections might potentially result from slight delays in macrophage-mediated wound healing due to vedolizumab-mediated inhibition of non-classical monocyte homing, finally leading to increased pathogen translocation and subsequent infection of adjacent tissues.…”

Section: Discussionmentioning

confidence: 75%

Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing

Schleier

Wiendl

Heidbreder

et al. 2019

Gut

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ObjectiveTo study the role of α4β7 integrin for gut homing of monocytes and to explore the biological consequences of therapeutic α4β7 inhibition with regard to intestinal wound healing.DesignWe studied the expression of homing markers on monocyte subsets in the peripheral blood and on macrophage subsets in the gut of patients with IBD and controls with flow cytometry and immunohistochemistry. Integrin function was addressed with dynamic adhesion assays and in vivo gut homing assays. In vivo wound healing was studied in mice deficient for or depleted of α4β7 integrin.ResultsClassical and non-classical monocytes were clearly dichotomous regarding homing marker expression including relevant expression of α4β7 integrin on human and mouse non-classical monocytes but not on classical monocytes. Monocyte-expressed α4β7 integrin was functionally important for dynamic adhesion to mucosal vascular addressin cell adhesion molecule 1 and in vivo gut homing. Impaired α4β7-dependent gut homing was associated with reduced (effect size about 20%) and delayed wound healing and suppressed perilesional presence of wound healing macrophages. Non-classical monocytes in the peripheral blood were increased in patients with IBD under clinical treatment with vedolizumab.ConclusionIn addition to reported effects on lymphocytes, anti-α4β7 therapy in IBD also targets non-classical monocytes. Impaired gut homing of such monocytes might lead to a reduction of wound healing macrophages and could potentially explain increased rates of postoperative complications in vedolizumab-treated patients, which have been observed in some studies.

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Section: Discussionmentioning

confidence: 75%

Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing

Schleier

Wiendl

Heidbreder

et al. 2019

Gut

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“…Four required colectomy, and at 14 weeks, 13 of 17 children followed up were in remission according to PUCAI score. Other reports from single centres report higher rates of colectomy than these larger studies. Our report is of a much tighter defined cohort than these larger studies as the 4 children were all facing imminent colectomy.…”

Section: Characteristics and Response Of Children To Vedolizumab For mentioning

confidence: 51%

“…Zimmerman et al. raised concerns that children with IBD who received Vedolizumab prior to surgery had a higher prevalence of post‐operative complications, particularly mucocutaneous stoma separation, than children having similar surgery who had not been exposed to Vedolizumab . This finding was not replicated in the similar sized paediatric cohort of Lightner et al.…”

Section: Characteristics and Response Of Children To Vedolizumab For mentioning

confidence: 99%

Response to vedolizumab for children with steroid‐refractory Ulcerative Colitis unresponsive to anti‐TNF

2019

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“…[19]. On the other hand, there are concerns that VDZ has been raised post-operative complications due to its ability to inhibit leucocyte migration which is an important process for wound healing [20]. As this case reports the detailed findings of one patient, further studies must properly establish the safety and efficacy of VDZ in children, and the results may lead to a better choice of biologics for pediatric UC.…”

Section: Discussionmentioning

confidence: 88%

A pediatric case of moderate active ulcerative colitis successfully treated with vedolizumab in Japan

Ikeuchi

Kakiuchi

Ibi

et al. 2020

Clin J Gastroenterol

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Corticosteroids and biologics are used to treat moderate-to-severe active pediatric ulcerative colitis (UC); however, it is often difficult to continue administration because of systemic side reactions. Vedolizumab is considered to have few adverse effects due to its mechanism of action and it is expected to be used in children, but the long-term administration of vedolizumab to Japanese pediatric patients with UC has not been reported. We report a case of pediatric moderate active UC with anti-tumor necrosis factor-failure that was successfully treated with vedolizumab in Japan.

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Postoperative complications of pediatric patients with inflammatory bowel disease treated with vedolizumab

Cited by 24 publications

References 12 publications

Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing

Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing

Response to vedolizumab for children with steroid‐refractory Ulcerative Colitis unresponsive to anti‐TNF

A pediatric case of moderate active ulcerative colitis successfully treated with vedolizumab in Japan

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