Effects of Vedolizumab in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases

Lynch, Kate D.; Chapman, Roger W.; Keshav, Satish; Montaño-Loza, Aldo J.; Mason, Andrew L.; Kremer, Andreas E.; Vetter, Marcel; Krijger, Manon de; Ponsioen, Cyriel Y.; Trivedi, Palak; Hirschfield, Gideon; Schramm, Christoph; Liu, Chung Heng; Bowlus, Christopher L.; Estes, Derek; Pratt, Daniel S.; Hedin, Charlotte; Bergquist, Annika; Vries, Annemarie C. de; Woude, C. Janneke van der; Lei, Yu; Assis, David N.; Boyer, James L.; Ytting, Henriette; Hallibasic, Emina; Trauner, Michael; Marschall, Hanns‐Ulrich; Daretti, L.M.; Marzioni, Marco; Yimam, Kidist; Perin, Nicola; Floreani, Annarosa; Beretta‐Piccoli, Benedetta Terziroli; Rogers, Jennifer K.; Levy, Cynthia

doi:10.1016/j.cgh.2019.05.013

Cited by 72 publications

(55 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…111,112 However, these series showed conflicting results regarding changes in alkaline phosphatase levels as a surrogate endpoint for liver disease activity. 111,[113][114][115] It must be noted that there were different limitations in these studies. The studies consisted of small numbers and heterogeneous groups, including both patients with and without ursodeoxycholic acid treatment, which could dampen the effect of changes in alkaline phosphatase.…”

Section: Vedolizumabmentioning

confidence: 96%

Return to sender: Lymphocyte trafficking mechanisms as contributors to primary sclerosing cholangitis

Krijger

Wildenberg

Jonge

et al. 2019

Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

Primary sclerosing cholangitis (PSC) is an inflammatory disease of the biliary tree, characterised by stricturing bile duct disease and progression to liver fibrosis. The pathophysiology of PSC is still unknown. The concurrence with inflammatory bowel disease (IBD) in about 70% of cases has led to the hypothesis that gut-homing lymphocytes aberrantly traffic to the liver, contributing to disease pathogenesis in patients with both PSC and IBD (PSC-IBD). The discovery of mutual trafficking pathways of lymphocytes to target tissues, and expression of gut-specific adhesion molecules and chemokines in the liver has pointed in this direction. There is now increasing interest in using drugs that intervene with these trafficking pathways (e.g. vedolizumab, etrolizumab) for the treatment of PSC-IBD. In this review we discuss what is currently known about the immunological interactions between the gut and the liver in concomitant PSC and IBD, as well as potential therapeutic options for intervening in these mechanisms.

show abstract

Section: Vedolizumabmentioning

confidence: 96%

Return to sender: Lymphocyte trafficking mechanisms as contributors to primary sclerosing cholangitis

Krijger

Wildenberg

Jonge

et al. 2019

Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite theoretically promising, the use of Vedolizumab, which antagonize MAdCAM-1 and its receptor α4β7 and it is approved for IBD treatment, did not show efficacy in patients with PSC and IBD (a phase 3 trial was retired in 2018). A retrospective study on Vedolizumab in patients with PSC and IBD also failed to reveal a positive signal (96).…”

Section: Modulation Of the Microbiota And Gut-liver Axismentioning

confidence: 98%

New Therapeutic Targets in Autoimmune Cholangiopathies

et al. 2020

View full text Add to dashboard Cite

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune cholangiopathies characterized by limited treatment options. A more accurate understanding of the several pathways involved in these diseases has fostered the development of novel and promising targeted drugs. For PBC, the characterization of the role of farnesoid X receptor (FXR) and perixosome-proliferator activated receptor (PPAR) has paved the way to several clinical trials including different molecules with choleretic and antinflammatory action. Conversely, different pathogenetic models have been proposed in PSC such as the "leaky gut" hypothesis, a dysbiotic microbiota or a defect in mechanisms protecting against bile acid toxicity. Along these theories, new treatment approaches have been developed, ranging from drugs interfering with trafficking of lymphocytes from the gut to the liver, fecal microbiota transplantation or new biliary acids with possible immunomodulatory potential. Finally, for both diseases, antifibrotic agents are under investigation. In this review, we will illustrate current understanding of molecular mechanisms in PBC and PSC, focusing on actionable biological pathways for which novel treatments are being developed.

show abstract

“…CCL25, CCL28 and CXCL12) are detected in the portal areas [171][172][173], suggesting vedolizumab may represent a putative therapeutic agent in PSC. However, results of a small retrospective study (n = 34) and subsequently a larger international retrospective study (n = 102) in patients with PSC and IBD have been disappointing, showing no evidence for significant improvement of liver biochemistry in PSC [174,175]. Whether a dedicated trial of vedolizumab in PSC will be performed, is thus doubtful.…”

Section: Biologics In the Treatment Of Pscmentioning

confidence: 99%

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

Vesterhus

Karlsen

2020

J Gastroenterol

View full text Add to dashboard Cite

show abstract

Effects of Vedolizumab in Patients With Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases

Cited by 72 publications

References 30 publications

Return to sender: Lymphocyte trafficking mechanisms as contributors to primary sclerosing cholangitis

Return to sender: Lymphocyte trafficking mechanisms as contributors to primary sclerosing cholangitis

New Therapeutic Targets in Autoimmune Cholangiopathies

Emerging therapies in primary sclerosing cholangitis: pathophysiological basis and clinical opportunities

Contact Info

Product

Resources

About