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The Future of PBC Treatment
The Future of PBC Treatment Is Now

Released: November 24, 2025

Gideon Hirschfield
Gideon Hirschfield, MA, MB BChir, FRCP, PhD
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Key Takeaways
  • New second-line therapies have the potential to improve symptoms as well as biochemical response.
  • Now more than ever, primary biliary cholangitis care is focused on addressing endpoints that are meaningful to patients, as well as biochemical control of the disease.

These are quite exciting times in the primary biliary cholangitis (PBC) field, compared to days gone by. The range of treatment choices for people with PBC has increased enormously, and accordingly, the goals of treatment are now much more aspirational. The field has made progress in symptom management as well as biochemical control of the disease.

New Second-line Therapies on Deck
We now know that the ideal treatment goal is to have normal liver tests and no symptoms. I still use ursodeoxycholic acid as first-line therapy and I still recommend that for all people with PBC, but I am much more proactive about assessing for biochemical control of disease after 6-12 months of therapy.

If first-line therapy provides inadequate biochemical control of disease or symptoms, in particular itch, I then look to second-line therapies. In the US, elafibranor and seladelpar are the current approved second-line therapies. They are indicated for people with insufficient biochemical response after first-line therapy and can also be considered for people with insufficient symptom improvement with first-line therapy. Both of these drugs are  peroxisome proliferator–activated receptor agonists and have demonstrated the potential to improve pruritus.

Second-line Therapies in the Pipeline
Linerixibat, an oral ileal bile acid transporter (IBAT) inhibitor, is another exciting new therapy in the pipeline. IBAT inhibitors increase bile acid delivery to the colon, thereby resulting in their excretion, rather than recirculating to the liver.

In recently published phase III clinical trial results, we reported that in people with PBC, pruritus was significantly improved with investigational linerixibat compared to placebo over 6 months of treatment. This trial was dedicated to the treatment of itch and was actually very large by PBC standards.

These recently published results mirror what has been reported with other IBAT inhibitors that are already in use for treatment of pruritus in pediatric liver disease. I am quite confident that these recent findings indicate that these investigational drugs will be used to manage pruritus in adults with PBC. Ultimately, these results give me hope that, as early as 2026, there will be safe and simple treatment options specifically for people with PBC who have pruritus, regardless of biochemical disease activity.

I believe that demonstrating that we can treat pruritus in PBC illustrates that we can also find ways to improve other aspects of quality of life. For example, I do recognize that my patients with PBC have fatigue and would like to have therapies that improve it. In fact, there are clinical trials ongoing for treatment of fatigue in PBC, with novel agents targeting neuronal signaling, for example.

Next Up in PBC Treatment
In all, I think the future for treating PBC is bright, and staying current is crucial for optimizing best practice. I think our goals of preventing liver transplantation and making patients feel better through symptom management are deliverable and achievable. With new second-line therapies and more on the horizon, healthcare professionals and patients can now have a much more dynamic dialogue to figure out how to achieve ideal biochemical control and ideal control of their symptoms. 

Your Thoughts
How has approval of new second-line therapies affected your approach to management of PBC? Or how do you anticipate it changing? Leave a comment to join the discussion and register for our live webinar to learn more!

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