TY - JOUR
T1 - UK-Wide Multicenter Evaluation of Second-line Therapies in Primary Biliary Cholangitis
AU - Abbas, Nadir
AU - Culver, Emma L.
AU - Thorburn, Douglas
AU - Halliday, Neil
AU - Crothers, Hannah
AU - Dyson, Jessica K.
AU - Phaw, April
AU - Aspinall, Richard
AU - Khakoo, Salim I.
AU - Kallis, Yiannis
AU - Smith, Belinda
AU - Patanwala, Imran
AU - McCune, Anne
AU - Chimakurthi, Chenchu R.
AU - Hegade, Vinod
AU - Orrell, Michael
AU - Jones, Rebecca
AU - Mells, George
AU - Thain, Colette
AU - Thain, Robert-Mitchell
AU - Jones, David
AU - Hirschfield, Gideon
AU - Trivedi, Palak J.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
KW - Bezafibrate
KW - Cirrhosis
KW - Fenofibrate
KW - Fibric Acid
KW - Obeticholic Acid
KW - Cholestasis
KW - Farnesoid-X-receptor (FXR)
KW - Fibrates
KW - Peroxisome Proliferator Activated Receptor (PPAR)
U2 - 10.1016/j.cgh.2022.07.038
DO - 10.1016/j.cgh.2022.07.038
M3 - Article
SN - 1542-3565
VL - 21
SP - 1561-1570.e13
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 6
ER -