Vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve liver biochemistry but is safe and effective for the bowel disease

Abstract

Summary Background Blocking of lymphocyte trafficking to bile ducts is a potential mechanism to alter the disease course of patients with primary sclerosing cholangitis (PSC). Aim To describe the effect of the α4β7 integrin antibody, vedolizumab, on liver biochemistry and disease activity in patients with PSC and inflammatory bowel disease (IBD). Methods This is a retrospective multi-center study of adult patients with a diagnosis of both IBD and PSC. The primary outcome was change in serum alkaline phosphatase level at weeks 14 and 30. Secondary outcomes included changes in other liver biochemistries and in clinical outcomes for the bowel disease. A safety analysis for adverse events was performed. Results 34 patients (16 Crohn’s disease, 18 ulcerative colitis) were included. Nine (26%) had a history of liver transplant. Median follow-up on vedolizumab was 9 months [IQR: 7–16]. There was no overall change in serum alkaline phosphatase level with vedolizumab therapy (median 268 [IQR:105–551] IU/L at baseline versus 249 [IQR:183–634] IU/L, P=0.99 at week 30). No significant changes in other liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. Clinical remission was achieved at week 30 in 55% of Crohn’s disease and 29% of ulcerative colitis patients. Seven (21%) patients ceased vedolizumab; six patients stopped therapy due to persistent IBD activity and one for worsening of liver biochemistries. Conclusion Vedolizumab treatment in patients with PSC and IBD did not improve liver biochemistry but was associated with improvement in bowel disease and a favorable safety profile.

Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease

“…Our study's findings regarding the lack of efficacy of infliximab and vedolizumab to reduce liver enzymes are in consensus with prior studies, including a prospective controlled trial for infliximab . While both infliximab and adalimumab are anti‐TNFα monoclonal antibodies, infliximab is chimeric (25% murine) and adalimumab is fully human, and they differ in the routes of administration and mechanics of absorption, distribution and elimination .…”

“…Vedolizumab, in theory, has a possible biological rationale to interfere with the pathogenesis of PSC through its inhibition of the α4β7 integrin expressed on lymphocytes with resultant impairment of lymphocyte gut trafficking . Several small studies have explored the effects of anti‐TNFα agents and vedolizumab on reducing biliary inflammation: neither infliximab nor vedolizumab were found to be effective, while adalimumab potentially decreased the alkaline phosphatase (ALP) level . While ursodeoxycholic acid (UDCA) improves hepatic biochemistries (LFTs) in 20%‐25% of PSC patients, it has not been shown to alter the progression of PSC …”

Novel and emerging therapies for cholestatic liver diseases

“…A retrospective study of 34 PSC patients receiving vedoluzimab for concomitant IBD [16 with Crohn's disease (CD) and 8 with ulcerative colitis (UC)] did not demonstrate a decline in liver chemistries or Mayo PSC risk score at 30 weeks. However, 55% and 29% of CD and UC patients, respectively, reached clinical remission of their IBD symptoms …”

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

“…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.…”