Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis

TY - JOUR

T1 - Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis

AU - Hedin, Charlotte Rose Hawkey

AU - Sado, Gina

AU - Ndegwa, Nelson

AU - Lytvyak, Ellina

AU - Mason, Andrew

AU - Montano-Loza, Aldo

AU - Gerussi, Alessio

AU - Saffioti, Francesca

AU - Thorburn, Douglas

AU - Nilsson, Emma

AU - Larsson, Geir

AU - Moum, Bjørn A

AU - van Munster, Kim N

AU - Ponsioen, Cyriel Y

AU - Levy, Cynthia

AU - Nogueira, Nicholas F

AU - Bowlus, Christopher L

AU - Gotlieb, Neta

AU - Shibolet, Oren

AU - Lynch, Kate D

AU - Chapman, Roger W

AU - Rupp, Christian

AU - Vesterhus, Mette

AU - Jørgensen, Kristin K

AU - Rorsman, Fredrik

AU - Schramm, Christoph

AU - Sabino, João

AU - Vermeire, Severine

AU - Zago, Alessandra

AU - Cazzagon, Nora

AU - Marschall, Hanns-Ulrich

AU - Ytting, Henriette

AU - Ben Belkacem, Karima

AU - Chazouilleres, Olivier

AU - Almer, Sven

AU - Bergquist, Annika

AU - International PSC Study Group (IPSCSG)

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

PY - 2020/9

Y1 - 2020/9

N2 - BACKGROUND & AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD.METHODS: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy.RESULTS: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083).CONCLUSIONS: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.

AB - BACKGROUND & AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD.METHODS: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy.RESULTS: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083).CONCLUSIONS: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.

U2 - 10.1016/j.cgh.2020.02.014

DO - 10.1016/j.cgh.2020.02.014

M3 - SCORING: Journal article

C2 - 32068151

VL - 18

SP - 2295-2304.e2

JO - CLIN GASTROENTEROL H

JF - CLIN GASTROENTEROL H

SN - 1542-3565

IS - 10

ER -