Real-World Clinical Management of Patients with Primary Biliary Cholangitis—A Retrospective Multicenter Study from Germany

Abstract

Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 x upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3% of patients, respectively. In 83.8% of patients, ALP ≤ 1.67 x ULN were achieved. A total of 116 patients (24.2%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60%, p = 0.005), Barcelona (13 vs. 34%, p = 0.0005), ALP ≤ 1.67 x ULN and bilirubin ≤ 1 x ULN (52.1 vs. 75%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74%, p = 0.004; Barcelona: 50 vs. 84%, p = 0.046; ALP < 1.67x ULN and bilirubin ≤ 1 × ULN: 33 vs. 86%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.

Real-World Management of Patients with Primary Biliary Cholangitis—A Retrospective Study from a Tertiary Medical Center in Israel

“…Biochemical non-response to UDCA is a well-known predictor of long-term histological progression [ 10 ]. UDCA response rates in our cohort were found to be generally similar to previous reports, yet higher in comparison to recent similar studies [ 21 , 22 ]. According to the Barcelona criterion, we have documented a non-response rate of 40.6%, while multicenter data from Portugal and Germany reported rates of 30.7% and 38.7%, respectively [ 21 , 22 ].…”

“…UDCA response rates in our cohort were found to be generally similar to previous reports, yet higher in comparison to recent similar studies [ 21 , 22 ]. According to the Barcelona criterion, we have documented a non-response rate of 40.6%, while multicenter data from Portugal and Germany reported rates of 30.7% and 38.7%, respectively [ 21 , 22 ]. In addition, when assessing response rates according to the Toronto criterion, we found a non-response rate of 28.1%, while a recently published German study found a non-response rate of only 16.2% according to this criterion [ 22 ].…”

“…According to the Barcelona criterion, we have documented a non-response rate of 40.6%, while multicenter data from Portugal and Germany reported rates of 30.7% and 38.7%, respectively [ 21 , 22 ]. In addition, when assessing response rates according to the Toronto criterion, we found a non-response rate of 28.1%, while a recently published German study found a non-response rate of only 16.2% according to this criterion [ 22 ]. These higher percentages of UDCA non-response in our study could be attributed to the accumulation of difficult to treat patients in a referral tertiary center [ 17 ].…”

Novel therapeutic targets for cholestatic and fatty liver disease

“…Real world data confirmed the efficacy and safety of OCA in PBC with lower efficacy and reduced tolerability in patients with cirrhosis. 98 99 Notably, use of OCA was associated with an increase in hepatic decompensation in patients with compensated PBC cirrhosis. 100 which led to an update of the PBC label with a contraindication for use in patients with decompensated cirrhosis, a prior decompensation event or with compensated cirrhosis and evidence of portal hypertension.…”

Special Issue “New Therapies of Liver Diseases”

“…Two studies investigated the current and future management of cholestatic liver diseases [ 4 , 5 ]. The first study retrospectively evaluated the real-world clinical management of patients with primary biliary cholangitis (PBC), according to the indications of the recent updated clinical guidelines.…”