Second-line treatment of primary biliary cholangitis: To whom, which molecule, and when

Ursodeoxycholic acid (UDCA) is the first-line treatment of primary biliary cholangitis (PBC). Approximately two-thirds of patients have a biochemical response to UDCA, but only one-third of treated patients achieve a complete biochemical response. UDCA nonresponse is associated with hepatic decompensation and higher liver-related mortality; therefore, UDCA nonresponders should be considered for second-line PBC treatment. Nonfibrate peroxisome proliferator-activated receptor (PPAR) agonists elafibranor and seladelpar are approved for second-line PBC treatment in UDCA nonresponders and in UDCA treatment intolerance. Fibrates are an alternative second-line PBC therapy, but they are not approved for second-line treatment. A significant benefit of PPAR receptor agonists therapy is the alleviation of pruritus in some patients. Second-line PBC treatment is usually indicated after 1 year of UDCA therapy; however, it may be considered after 6 months of UDCA treatment in high-risk PBC patients. The selection of drug for second-line PBC treatment and the timing of therapy initiation should be individualized. Many factors, including PBC complications, especially pruritus, should also be considered in the decision-making algorithm. It will be necessary in the coming years to evaluate the efficacy of PPAR agonists in real-world clinical practice, including monitoring the incidence of decompensated liver cirrhosis and liver-related mortality.