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UK-wide multicenter evaluation of second-line therapies in primary biliary cholangitis

UK-wide multicenter evaluation of second-line therapies in primary biliary cholangitis
UK-wide multicenter evaluation of second-line therapies in primary biliary cholangitis

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021. Results: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P <.05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P <.001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P <.001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P =.121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. Conclusion: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.

Alanine Transaminase, Alkaline Phosphatase, Bilirubin, Cholangitis/drug therapy, Fibric Acids/therapeutic use, Humans, Liver Cirrhosis, Biliary/drug therapy, Ursodeoxycholic Acid/therapeutic use, Peroxisome Proliferator Activated Receptor (PPAR), Farnesoid-X-receptor (FXR), Obeticholic Acid, Fenofibrate, Fibric Acid, Cirrhosis, Bezafibrate, Fibrates, Cholestasis
1542-3565
1561-1570.e13
Abbas, Nadir
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Culver, Emma L.
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Thorburn, Douglas
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Halliday, Neil
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Crothers, Hannah
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Dyson, Jessica K.
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Phaw, April
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Aspinall, Richard
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Khakoo, Salim I.
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Kallis, Yiannis
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Smith, Belinda
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Patanwala, Imran
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McCune, Anne
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Chimakurthi, Chenchu R.
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Hegade, Vinod
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Orrell, Michael
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Jones, Rebecca
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Mells, George
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Thain, Colette
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Thain, Robert-Mitchell
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Jones, David
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Hirschfield, Gideon
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Trivedi, Palak J.
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Abbas, Nadir
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Culver, Emma L.
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Thorburn, Douglas
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Halliday, Neil
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Crothers, Hannah
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Dyson, Jessica K.
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Phaw, April
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Aspinall, Richard
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Khakoo, Salim I.
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Kallis, Yiannis
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Smith, Belinda
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Patanwala, Imran
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McCune, Anne
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Chimakurthi, Chenchu R.
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Hegade, Vinod
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Orrell, Michael
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Jones, Rebecca
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Mells, George
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Thain, Colette
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Thain, Robert-Mitchell
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Jones, David
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Hirschfield, Gideon
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Trivedi, Palak J.
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Abbas, Nadir, Culver, Emma L., Thorburn, Douglas, Halliday, Neil, Crothers, Hannah, Dyson, Jessica K., Phaw, April, Aspinall, Richard, Khakoo, Salim I., Kallis, Yiannis, Smith, Belinda, Patanwala, Imran, McCune, Anne, Chimakurthi, Chenchu R., Hegade, Vinod, Orrell, Michael, Jones, Rebecca, Mells, George, Thain, Colette, Thain, Robert-Mitchell, Jones, David, Hirschfield, Gideon and Trivedi, Palak J. (2023) UK-wide multicenter evaluation of second-line therapies in primary biliary cholangitis. Clinical Gastroenterology and Hepatology, 21 (6), 1561-1570.e13. (doi:10.1016/j.cgh.2022.07.038).

Record type: Article

Abstract

Background & Aims: Thirty-to-forty percent of patients with primary biliary cholangitis inadequately respond to ursodeoxycholic acid. Our aim was to assemble national, real-world data on the effectiveness of obeticholic acid (OCA) as a second-line treatment, alongside non-licensed therapy with fibric acid derivatives (bezafibrate or fenofibrate). Methods: This was a nationwide observational cohort study conducted from August 2017 until June 2021. Results: We accrued data from 457 patients; 349 treated with OCA and 108 with fibric acid derivatives. At baseline/pre-treatment, individuals in the OCA group manifest higher risk features compared with those taking fibric acid derivatives, evidenced by more elevated alkaline phosphatase values, and a larger proportion of individuals with cirrhosis, abnormal bilirubin, prior non-response to ursodeoxycholic acid, and elastography readings >9.6kPa (P <.05 for all). Overall, 259 patients (OCA) and 80 patients (fibric acid derivatives) completed 12 months of second-line therapy, yielding a dropout rate of 25.7% and 25.9%, respectively. At 12 months, the magnitude of alkaline phosphatase reduction was 29.5% and 56.7% in OCA and fibric acid groups (P <.001). Conversely, 55.9% and 36.4% of patients normalized serum alanine transaminase and bilirubin in the OCA group (P <.001). The proportion with normal alanine transaminase or bilirubin values in the fibric acid group was no different at 12 months compared with baseline. Twelve-month biochemical response rates were 70.6% with OCA and 80% under fibric acid treatment (P =.121). Response rates between treatment groups were no different on propensity-score matching or on sub-analysis of high-risk groups defined at baseline. Conclusion: Across the population of patients with primary biliary cholangitis in the United Kingdom, rates of biochemical response and drug discontinuation appear similar under fibric acid and OCA treatment.

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e-pub ahead of print date: 9 August 2022
Published date: June 2023
Additional Information: Publisher Copyright: © 2023 The Authors
Keywords: Alanine Transaminase, Alkaline Phosphatase, Bilirubin, Cholangitis/drug therapy, Fibric Acids/therapeutic use, Humans, Liver Cirrhosis, Biliary/drug therapy, Ursodeoxycholic Acid/therapeutic use, Peroxisome Proliferator Activated Receptor (PPAR), Farnesoid-X-receptor (FXR), Obeticholic Acid, Fenofibrate, Fibric Acid, Cirrhosis, Bezafibrate, Fibrates, Cholestasis

Identifiers

Local EPrints ID: 484925
URI: http://eprints.soton.ac.uk/id/eprint/484925
ISSN: 1542-3565
PURE UUID: a5a00ee6-2351-457c-a70f-d88055520d18
ORCID for Salim I. Khakoo: ORCID iD orcid.org/0000-0002-4057-9091

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Date deposited: 24 Nov 2023 17:39
Last modified: 18 Mar 2024 02:55

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Contributors

Author: Nadir Abbas
Author: Emma L. Culver
Author: Douglas Thorburn
Author: Neil Halliday
Author: Hannah Crothers
Author: Jessica K. Dyson
Author: April Phaw
Author: Richard Aspinall
Author: Salim I. Khakoo ORCID iD
Author: Yiannis Kallis
Author: Belinda Smith
Author: Imran Patanwala
Author: Anne McCune
Author: Chenchu R. Chimakurthi
Author: Vinod Hegade
Author: Michael Orrell
Author: Rebecca Jones
Author: George Mells
Author: Colette Thain
Author: Robert-Mitchell Thain
Author: David Jones
Author: Gideon Hirschfield
Author: Palak J. Trivedi

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