How do you choose between a PPAR agonist, obeticholic acid, or a fibrate as second-line therapy in PBC with optimized ursodeoxycholic acid when the immediate priority is clinically significant pruritus but you also want to optimize long-term biochemical risk reduction?

I would prioritize the disease-modifying treatments first for their ability to modify the course of the disease, while at the same time, they may also alleviate pruritus. Elafibranor, for example, has had some antipruritic effects.

Obeticholic acid (OCA/Ocaliva) was voluntarily withdrawn from the U.S. market in September 2025 following FDA safety concerns, making it unavailable as a practical option. It's also known to worsen pruritus. Currently, the preferred second-line therapies are two PPAR agonists—seladelpar (a PPARδ agonist) and elafibranor (a PPARα/δ agonist)—approved in June 2024. In patients with pruritus, seladelpar is preferred, as seladelpar has shown statistically significant improvement in pruritus in clinic...