INTRODUCTION
abnormal serum liver tests, inflammation, granulomatous lymphocytic cholangitis, cholestatic, liver injury, bile duct injury/cholangitis, fibrosing liver injury, PBC, cholestasis, pruritus, NASH, primary biliary cholangitis, hepatitis, Histologic damage
DISEASE PROGRESSION, PBC, PRIMARY BILIARY CHOLANGITIS, INFLAMMATION, DISEASE, CHOLESTASIS, HEPATITIS
People living with primary biliary cholangitis (PBC) frequently have impaired quality and quantity of life, resulting from a chronic autoimmune-mediated, cholestatic, and fibrosing liver injury.Histologic damage characterized by a granulomatous lymphocytic cholangitis is associated with abnormal serum liver tests, including elevated serum alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aminotransferase activity, and total bilirubin.Seladelpar is a potent and selective peroxisome proliferator-activated receptor (PPARδ) agonist that has been shown to decrease levels of biochemical markers of cholestasis, liver injury, and inflammation in patients with PBC.The objective of this phase 3 study was to evaluate the safety of seladelpar 5 and 10 mg QD and to assess its effect on ALP, total bilirubin, biochemical markers of disease, and pruritus in patients with PBC at high risk for disease progression. The study originally aimed to evaluate treatment through 12 months; however, it was terminated early due to unexpected histological findings (ie, portal inflammation and interface hepatitis with plasma cells, bile duct injury/cholangitis, vascular changes, and other miscellaneous findings) in a concurrent study of seladelpar in patients with NASH (NCT03551522). A detailed independent investigation by a committee of pathologists and hepatologists determined that the histological findings following seladelpar treatment in the NASH trial did not differ qualitatively from baseline and were unrelated to seladelpar.