The Use of Biologics in Patients with Inflammatory Bowel Disease and Primary Sclerosing Cholangitis
PURPOSE OF REVIEW:
Biologics are well established in the treatment of many immuno-inflammatory diseasesincluding inflammatory bowel disease (IBD). However, although primary sclerosing cholangitis (PSC) is closely associated with IBD, the role of biologics in PSC remains uncertain. Many new biologics are becoming available to treat IBD, and this review aims to use the experience of biologics in PSC so far to guide more effective evaluation of emerging therapies in the future.
Antibodies to TNF-α were the first biologics used in IBD, and retrospective analysis suggests that they may have some benefit in PSC, even though an early randomised controlled trial (RCT) showed no effect. Mechanistic studies suggest that TNF-α may have a pathogenic role in PSC. An antibody to integrin α4β7 is effective in IBD, and there are emerging data on its effects in PSC, although no RCT data are available. Mechanistic studies suggest that interrupting the migration of lymphocytes is relevant in PSC. Two biologics, targeting vascular adhesion protein-1 (VAP-1), and lysyl oxidase-like 2 (LOXL2) have been tested in RCTs. The trial of anti-VAP1 is ongoing, whilst the anti-LOXL2 trial was negative.
Anti-TNF antibodies may benefit PSC when used to treat concomitant IBD, and this may be a direct effect on the liver in a subgroup of patients, or may be an indirect effect of treating IBD. Similarly, anti-integrin therapy may benefit a subset of patients with IBD and PSC. RCTs could decide the role of emerging biologics in PSC, although future trials should be guided by biomarkers that could predict response to the pathway being targeted.
Lynch KD1, Keshav S1, Chapman RW1. Curr Hepatol Rep. 2019;18(1):115-126. doi: 10.1007/s11901-019-00456-2. Epub 2019 Mar 7.
1. Translational Gastroenterology Unit, Nuffield Department of Medicine, Level 5, John Radcliffe Hospital, University of Oxford, Headley Way, Headington, Oxford, OX3 9DU UK.