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

TY - JOUR

T1 - Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases.

AU - Lynch, Kate D

AU - Chapman, Roger W

AU - Keshav, Satish

AU - Montano-Loza, Aldo J

AU - Mason, Andrew L

AU - Kremer, Andreas E

AU - Vetter, Marcel

AU - de Krijger, Manon

AU - Ponsioen, Cyriel Y

AU - Trivedi, Palak

AU - Hirschfield, Gideon

AU - Schramm, Christoph

AU - Liu, Chung Heng

AU - Bowlus, Christopher L

AU - Estes, Derek J

AU - Pratt, Daniel

AU - Hedin, Charlotte

AU - Bergquist, Annika

AU - de Vries, Annemarie C

AU - Janneke van der Woude, C

AU - Yu, Lei

AU - Assis, David N

AU - Boyer, James

AU - Ytting, Henriette

AU - Hallibasic, Emina

AU - Trauner, Michael

AU - Marschall, Hanns-Ulrich

AU - Daretti, Luigi M

AU - Marzioni, Marco

AU - Yimam, Kidist K

AU - Perin, Nicola

AU - Floreani, Annarosa

AU - Beretta-Piccoli, Benedetta Terziroli

AU - Rogers, Jennifer K

AU - Levy, Cynthia

AU - International PSC Study Group (IPSCSG)

N1 - Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

PY - 2020/1

Y1 - 2020/1

N2 - BACKGROUND & AIMS: Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.METHODS: We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n=102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.RESULTS: In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P=.018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P=.019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.CONCLUSIONS: In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.

AB - BACKGROUND & AIMS: Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.METHODS: We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n=102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.RESULTS: In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P=.018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P=.019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.CONCLUSIONS: In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.

KW - Journal Article

U2 - 10.1016/j.cgh.2019.05.013

DO - 10.1016/j.cgh.2019.05.013

M3 - SCORING: Journal article

C2 - 31100458

VL - 18

SP - 179-187.e6

JO - CLIN GASTROENTEROL H

JF - CLIN GASTROENTEROL H

SN - 1542-3565

IS - 1

ER -