Vedolizumab: a novel medical intervention in the treatment of primary sclerosing cholangitis

Westerveld, Donevan; Grajo, Joseph R.; Beattie, Lars K.; Glover, Sarah C.

doi:10.1136/bcr-2017-220351

Cited by 5 publications

(3 citation statements)

References 3 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

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

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

View full text Add to dashboard Cite

show abstract

“…To date, only small studies evaluated the effect of anti-integrin therapy with vedolizumab in patients with IBD and concomitant PSC. Despite showing efficacy in ameliorating IBD, the impact of vedolizumab on liver biochemistry was rather modest and disappointing [70][71][72]. One retrospective multicentre study of 34 PSC patients receiving vedolizumab for concomitant IBD demonstrated no overall change in serum AP, other liver biochemistry, or the Mayo PSC risk score after 30 weeks [72].…”

Section: Cytokine/chemokine Mediator Targeting Therapiesmentioning

confidence: 99%

Future Medical Treatment of PSC

Krones

Marschall

Fickert

2019

Curr Hepatology Rep

View full text Add to dashboard Cite

Purpose of Review Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder characterized by inflammation of intrahepatic and/or extrahepatic bile ducts leading to stricturing, biliary fibrosis, cirrhosis, and liver failure. PSC is highly associated with inflammatory bowel diseases (IBD) and bears significant risk for cholangiocellular and colorectal cancer. To date, no medical treatment has been proven in randomized controlled trials to improve transplant-free and overall patient survival. However, numerous innovative therapeutic concepts are currently tested in phase 2 to phase 3 clinical trials. Based on currently suggested pathogenetic mechanisms of PSC, such drugs target its immunopathogenesis and nuclear and membrane receptors regulating bile acid transport and metabolism, gut microbiota, and liver fibrosis. The purpose of this review is to discuss recent advances in targeted medical treatment options for PSC. Recent Findings While a large carefully designed phase 2b trial targeting fibrosis development in PSC failed (simtuzumab), another compound was promoted from phase 2a to phase 3 trial based on significant improvements of alkaline phosphatase (AP) and excellent safety profile (norursodeoxycholic acid, norUDCA). Summary Ongoing trials evaluate numerous different targets considered to be involved in PSC pathogenesis, with so far, no clear advantage of either compound. This must be attributed to the still unknown cause of PSC. It may turn out that only combination therapy may reach a breakthrough. The fact that numerous studies isochronally test the same drug or therapeutic concept like in the case of vancomycin or faecal microbiota transplantation (FMT) demands improved and coordinated international strategies for study design to develop more effective drug pipelines, which is one major target of the International PSC Study Group (IPSCSG).

show abstract

“…This combination therapy would need to be further studied with a much larger cohort to prove clinical significance. Additionally, a case report by Tischendorf et al showed radiographic and laboratory improvement in a patient with PSC after a 13 month course of the immunosuppressant vedolizumab [63]. The patient had clinical improvement with reduction in pruritus and abdominal pain secondary to PSC.…”

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

Virani

Akers

Stephenson

et al. 2018

J Liver

View full text Add to dashboard Cite

Cholestatic liver injury is characterized by damage induced on the biliary tree and cholangiocytes, the cells lining the biliary tree, thus they are termed “cholangiopathies”. Cholangiopathies include diseases such as Primary Biliary Cholangitis, Primary Sclerosing Cholangitis, Biliary Atresia and Cholangiocarcinoma. These pathologies lack viable therapies and most patients are diagnosed during late stage disease progression (with the exception of Biliary Atresia, which is found shortly after birth). The lack of therapies for these diseases has put a significant burden on the need for liver transplantation as this is the only indicative “cure” for cholangiopathies. The molecular mechanisms for cholangiopathies have been extensively studied; however, and unfortunately, the lack of effective biomarkers and therapeutics remains. In this review article we highlight the latest studies to investigate the molecular mechanisms regulating cholangiopathies and the potential therapeutics that might be discovered.

show abstract

Vedolizumab: a novel medical intervention in the treatment of primary sclerosing cholangitis

Cited by 5 publications

References 3 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

Future Medical Treatment of PSC

Comprehensive Review of Molecular Mechanisms during Cholestatic Liver Injury and Cholangiocarcinoma

Contact Info

Product

Resources

About