TY - JOUR
T1 - Fibrates for Itch (FITCH) in Fibrosing Cholangiopathies: A Double-Blind, Randomized, Placebo-Controlled Trial
AU - de Vries, Elsemieke
AU - Bolier, Ruth
AU - Goet, Jorn
AU - Parés, Albert
AU - Verbeek, Jef
AU - de Vree, Marleen
AU - Drenth, Joost
AU - van Erpecum, Karel
AU - Netherlands Association for the Study of the Liver-Cholestasis Working Group
AU - van Nieuwkerk, Karin
AU - van der Heide, Frans
AU - Mostafavi, Nahid
AU - Helder, Jeltje
AU - Ponsioen, Cyriel
AU - Oude Elferink, Ronald
AU - van Buuren, Henk
AU - Beuers, Ulrich
N1 - Funding Information: Funding The trial was funded by a South African PSC patient foundation (to U.B.), a Netherlands patient donation (to U.B.), a “Gastrostart” grant of the Netherlands Society of Gastroenterology covering 50% of drug manufacturing (to U.B.), and for management of patient inclusion in Barcelona grant PI15/797 from the Instituto de Salud Carlos III (to A.P.). Publisher Copyright: © 2021 AGA Institute Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Background and Aims: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury. The aim of this investigator-initiated FITCH trial (Fibrates for cholestatic ITCH) was to assess effects of bezafibrate on pruritus in patients with PSC, PBC, and SSC. Methods: Patients with moderate to severe pruritus (≥5 of 10 on visual analog scale [VAS]) due to PSC, PBC, or SSC were recruited for this double-blind, randomized, placebo-controlled trial between 2016 and 2019. Patients received once-daily bezafibrate (400 mg) or placebo for 21 days. The primary end point was ≥50% reduction of pruritus (VAS; intention-to-treat). Results: Of 74 randomized patients, 70 completed the trial (95%; 44 PSC, 24 PBC, 2 SSC). For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to ≥50% reduction of severe or moderate pruritus (P =.003). For secondary end points, bezafibrate reduced morning (P =.01 vs placebo) and evening (P =.007) intensity of pruritus (VAS) and improved the validated 5D-Itch questionnaire (P =.002 vs placebo). Bezafibrate also reduced serum alkaline phosphatase (−35%, P =.03 vs placebo) correlating with improved pruritus (VAS, P =.01) suggesting reduced biliary damage. Serum bile acids and autotaxin activity remained unchanged. Serum creatinine levels tended to mildly increase (3% bezafibrate, 5% placebo, P =.14). Conclusions: Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. Trial Registration: Netherlands Trial Register, ID: NTR5436 (August 3, 2015), ClinicalTrials.gov ID: NCT02701166 (March 2, 2016).
AB - Background and Aims: Pruritus may seriously impair quality of life in patients with cholestatic diseases such as primary or secondary sclerosing cholangitis (PSC, SSC) and primary biliary cholangitis (PBC). Pharmacologic strategies show limited efficacy and can provoke serious side effects. We hypothesized that bezafibrate, a broad peroxisome proliferator-activated receptor (PPAR) agonist, relieves cholestasis-associated itch by alleviating hepatobiliary injury. The aim of this investigator-initiated FITCH trial (Fibrates for cholestatic ITCH) was to assess effects of bezafibrate on pruritus in patients with PSC, PBC, and SSC. Methods: Patients with moderate to severe pruritus (≥5 of 10 on visual analog scale [VAS]) due to PSC, PBC, or SSC were recruited for this double-blind, randomized, placebo-controlled trial between 2016 and 2019. Patients received once-daily bezafibrate (400 mg) or placebo for 21 days. The primary end point was ≥50% reduction of pruritus (VAS; intention-to-treat). Results: Of 74 randomized patients, 70 completed the trial (95%; 44 PSC, 24 PBC, 2 SSC). For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to ≥50% reduction of severe or moderate pruritus (P =.003). For secondary end points, bezafibrate reduced morning (P =.01 vs placebo) and evening (P =.007) intensity of pruritus (VAS) and improved the validated 5D-Itch questionnaire (P =.002 vs placebo). Bezafibrate also reduced serum alkaline phosphatase (−35%, P =.03 vs placebo) correlating with improved pruritus (VAS, P =.01) suggesting reduced biliary damage. Serum bile acids and autotaxin activity remained unchanged. Serum creatinine levels tended to mildly increase (3% bezafibrate, 5% placebo, P =.14). Conclusions: Bezafibrate is superior to placebo in improving moderate to severe pruritus in patients with PSC and PBC. Trial Registration: Netherlands Trial Register, ID: NTR5436 (August 3, 2015), ClinicalTrials.gov ID: NCT02701166 (March 2, 2016).
KW - Cholestasis
KW - Primary Biliary Cholangitis (PBC)
KW - Primary Sclerosing Cholangitis (PSC)
KW - Pruritus
UR - http://www.scopus.com/inward/record.url?scp=85098171001&partnerID=8YFLogxK
U2 - https://doi.org/10.1053/j.gastro.2020.10.001
DO - https://doi.org/10.1053/j.gastro.2020.10.001
M3 - Article
C2 - 33031833
SN - 0016-5085
VL - 160
SP - 734-743.e6
JO - Gastroenterology
JF - Gastroenterology
IS - 3
ER -