BACKGROUND:Optimal care delivery for primary biliary cholangitis (PBC) has become challenging due to new therapies and more individualized biochemical treatment goals. AIM:To evaluate uptake of ursodeoxycholic acid (UDCA) and second-line therapy (SLT) in a nationwide PBC cohort and identify factors associated with suboptimal therapeutical management. METHODS:The Dutch PBC Cohort Study is a retrospective study including every identifiable patient with PBC in the Netherlands from 1990 onwards. Use of UDCA and SLT was assessed among patients in clinical follow-up on 1 January 2019. Biochemical response was defined as alkaline phosphatase (ALP) and aspartate aminotransferase (AST) ≤ 1.5 × ULN and total bilirubin (TB) ≤ ULN. SLT included off-label fibrates, budesonide and/or obeticholic acid (not reimbursed). RESULTS:In total, 2638 patients with PBC were included; median age was 64.0 (IQR 55.0-72.0) years, 2361 (89.5%) were female and 2143 (81.2%) were treated in a non-academic center. Overall, 2532 (96.0%) patients used UDCA. The recommended UDCA dose of ≥ 13 mg/kg/day was used by 1363/2205 (61.8%). Age (aOR 1.01, 95% CI 1.00-1.02, p = 0.02), body weight (aOR 1.04, 95% CI 1.03-1.05, p < 0.01) and biochemical response (aOR 1.35, 95% CI 1.09-1.67, p = 0.01) were associated with UDCA dosage < 13 mg/kg/day. Among patients with an incomplete response, 101/638 (15.8%) were prescribed SLT. Younger age, female sex, treatment in an academic centre and higher levels of ALP and AST were positively associated with use of SLT. CONCLUSIONS:During recent years, UDCA was insufficiently dosed in Dutch patients with PBC. The results indicate that first-line treatment can be optimized, especially in those with a biochemical response and higher body weight.

INTRODUCTION: Off-label bezafibrate is increasingly used for primary biliary cholangitis (PBC) after randomized evidence of clinical efficacy. Evaluate the real-world experience with bezafibrate in PBC in relation to tolerability, response, and long-term outcome. METHODS: All patients initiating off-label bezafibrate in the Dutch PBC Cohort Study—a retrospective cohort study—were evaluated. Biochemical changes (Δ) during the first year of treatment were assessed, expressed in upper limits of normal (ULN). Dichotomous response was evaluated with the Paris II criteria and normal alkaline phosphatase (ALP). RESULTS: In total, 317 individuals (290 [91.5%] females) initiated bezafibrate therapy. Median baseline ALP was 2.30 (interquartile range [IQR] 1.52–3.36) and median total bilirubin (TB) 0.58 (IQR 0.41–0.92). At 12 months, the cumulative cessation rate was 24.6% (95% confidence interval [CI] 19.7–29.5); the minimal cessation rate due to side effects was 12.9%. The overall on-treatment median ΔALP and ΔTB at 12 months were −1.00 × ULN (IQR −1.50 to −0.49) and −0.06 × ULN (IQR −0.20 to 0.05), respectively. Normal ALP increased from 6% at baseline to 40% at 1 year, and Paris II fulfilment from 19% to 48% ( P < 0.001 both). The ΔALP at 1 year was 0.83 (IQR −1.25 to −0.53) in complete responders and −1.16 (IQR −2.34 to −0.45) in incomplete responders ( P = 0.078). Multivariable logistic regression showed that ALP (odds ratio 0.52, 95% CI 0.34–0.80) and AST (odds ratio 0.22, 95% CI 0.10–0.51) were negatively associated with the Paris II response. Ln(ALP in ULN) during bezafibrate treatment was associated with decompensation, liver transplantation, or death (hazard ratio 3.29, 95% CI 1.76–6.16, P < 0.001). DISCUSSION: In this real-world nationwide study, the 1-year fibrate discontinuation rate was substantial. However, off-label use of bezafibrate was associated with reductions in the biochemical markers of cholestasis in PBC, which were associated with clinical outcome in this setting of second-line therapy.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001). Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences. Impact and implications:: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population.