Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis
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Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis. / Soret, Pierre-Antoine; Lam, Laurent; Carrat, Fabrice; Smets, Lena; Berg, Thomas; Carbone, Marco; Invernizzi, Pietro; Leroy, Vincent; Trivedi, Palak; Cazzagon, Nora; Weiler-Normann, Christina; Alric, Laurent; Rosa-Hezode, Isabelle; Heurgué, Alexandra; Cervoni, Jean-Paul; Dumortier, Jérôme; Potier, Pascal; Roux, Olivier; Silvain, Christine; Bureau, Christophe; Anty, Rodolphe; Larrey, Dominique; Levy, Cynthia; Pares, Albert; Schramm, Christoph; Nevens, Frederik; Chazouillères, Olivier; Corpechot, Christophe.
In: ALIMENT PHARM THER, Vol. 53, No. 10, 05.2021, p. 1138-1146.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Combination of fibrates with obeticholic acid is able to normalise biochemical liver tests in patients with difficult-to-treat primary biliary cholangitis
AU - Soret, Pierre-Antoine
AU - Lam, Laurent
AU - Carrat, Fabrice
AU - Smets, Lena
AU - Berg, Thomas
AU - Carbone, Marco
AU - Invernizzi, Pietro
AU - Leroy, Vincent
AU - Trivedi, Palak
AU - Cazzagon, Nora
AU - Weiler-Normann, Christina
AU - Alric, Laurent
AU - Rosa-Hezode, Isabelle
AU - Heurgué, Alexandra
AU - Cervoni, Jean-Paul
AU - Dumortier, Jérôme
AU - Potier, Pascal
AU - Roux, Olivier
AU - Silvain, Christine
AU - Bureau, Christophe
AU - Anty, Rodolphe
AU - Larrey, Dominique
AU - Levy, Cynthia
AU - Pares, Albert
AU - Schramm, Christoph
AU - Nevens, Frederik
AU - Chazouillères, Olivier
AU - Corpechot, Christophe
N1 - © 2021 John Wiley & Sons Ltd.
PY - 2021/5
Y1 - 2021/5
N2 - BACKGROUND: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).AIM: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC.METHODS: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model.RESULTS: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group.CONCLUSIONS: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
AB - BACKGROUND: Obeticholic acid (OCA) and fibrates are second-line therapies for patients with primary biliary cholangitis (PBC) with an inadequate response to ursodeoxycholic acid (UDCA).AIM: To know whether OCA and fibrates, administered together in combination with UDCA, have additive beneficial effects in patients with difficult-to-treat PBC.METHODS: PBC patients treated for ≥3 months with UDCA, OCA and fibrates (bezafibrate or fenofibrate) due to failure of either second-line therapy were included in a multicentre, uncontrolled retrospective cohort study. Changes in biochemical liver tests and pruritus were analysed using a generalised linear mixed-effect model.RESULTS: Among 58 patients included, half received OCA as second-line and fibrates as third-line therapy (Group OCA-Fibrate), while the other half had the inverse therapeutic sequence (Group Fibrate-OCA). The mean duration of triple therapy was 11 months (range 3-26). Compared to dual therapy, triple therapy was associated with a significant gain in alkaline phosphatase (ALP) reduction: 22% per first year (95% CI 12%-31%), an effect that was stronger in OCA-Fibrate than in Fibrate-OCA group. Triple therapy was associated with a 3.4 (95% CI 1.4-8.2) odds ratio (OR) of reaching normal ALP and with a significant decrease in gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin. The ORs of achieving the Paris-2 and Toronto criteria of adequate biochemical response were 6.8 (95% CI 2.8-16.7) and 9.2 (95% CI 3.4-25.1) respectively. Finally, triple therapy significantly improved pruritus in OCA-Fibrate but not in Fibrate-OCA group.CONCLUSIONS: Triple therapy with UDCA, OCA and fibrates is able to normalise biochemical liver tests and improve pruritus in patients with difficult-to-treat PBC.
KW - Chenodeoxycholic Acid/analogs & derivatives
KW - Cholagogues and Choleretics/therapeutic use
KW - Fibric Acids/therapeutic use
KW - Humans
KW - Liver Cirrhosis, Biliary/drug therapy
KW - Retrospective Studies
KW - Ursodeoxycholic Acid/therapeutic use
U2 - 10.1111/apt.16336
DO - 10.1111/apt.16336
M3 - SCORING: Journal article
C2 - 33764590
VL - 53
SP - 1138
EP - 1146
JO - ALIMENT PHARM THER
JF - ALIMENT PHARM THER
SN - 0269-2813
IS - 10
ER -