Clayton, Mitchell

Background: Patients with primary sclerosing cholangitis (PSC) are at risk for developing gallbladder neoplasia (GBN) and biliary neoplasia, including cholangiocarcinoma (CCA), because of chronic inflammation and an underlying field effect. However, the risk of CCA after GBN detection in those with PSC remains poorly understood. We aimed to determine if the incidence of CCA is higher in those with GBN. Methods: We conducted a retrospective review of adult patients with large-duct PSC seen at Mayo Clinic between January 1, 1995, and December 31, 2019. Incidence rates for CCA development were calculated. Cox regression analyses were performed to determine features associated with CCA development beginning at the time of PSC diagnosis. Results: Our study included 1,829 patients with PSC. CCA and GBN developed in 334 (18.26%) and 71 individuals (3.88%), respectively. Among those with GBN, 14 (19.72%) developed CCA. The annual incidence of CCA was nearly twofold higher in patients with GBN (4.34% versus 2.21%). GBN was associated with CCA in an unadjusted analysis (hazard ratio 2.14 [95% CI 1.16–3.94]). When adjusting for other predictors of CCA, an association between GBN and CCA may remain. Conclusions: While few patients with PSC develop GBN, this subgroup is more likely to develop CCA. Consequently, once GBN is detected, clinicians should consider more intensive screening for CCA.

Abstract The purpose of this pilot study was to explore the efficacy, safety, and tolerability of vidofludimus calcium (VC) in the treatment of primary sclerosing cholangitis (PSC). This was a single‐arm open‐label pilot study with a cohort of 18 patients with PSC. Study patients received VC for a period of 6 months. The study was undertaken at two sites, Mayo Clinic, Rochester, MN, and Mayo Clinic, Phoenix, AZ. The primary endpoint of the study was improvement of serum alkaline phosphatase (ALP) at the end of the study. Secondary endpoints included assessment of other liver biomarkers (bilirubin, alanine aminotransferase, and aspartate aminotransferase). Of 18 patients enrolled, 11 completed the 6 months of study treatment. Patients who completed treatment versus those who did not were similar other than a significantly higher direct bilirubin at baseline in the group that completed treatment (mean ± SD, 0.4 ± 0.3 versus 0.1 ± 0.1, p = 0.04). By intent to treat analysis, the primary outcome was met in 16.7% (3/18) of patients. By per‐protocol analysis, including only patients who completed treatment, normalization of ALP occurred in 27.7% (3/11) at week 24 (95% confidence interval, 6.0% to 61.0%). VC was well tolerated with no drug‐related serious adverse events. Conclusion: This proof of concept study provides support for further exploration of VC in patients with PSC.