Ask AI
Back Back
Highlights From Innovations in PBC Care
Raising the Bar: Questions and Answers on Innovations in PBC Care

Released: December 18, 2025

Christopher L. Bowlus
Christopher L. Bowlus, MD
Aparna Goel
Aparna Goel, MD
Aliya Gulamhusein
Aliya Gulamhusein, MD, MPH, FRCPC
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Clinical trial data and anecdotal real-world data support PPAR agonists for treatment of PBC, but additional data are needed to determine if they improve fatigue, which would be truly groundbreaking for PBC care.

Recent advances in primary biliary cholangitis (PBC) care, including FDA approval of 2 new agents for second-line therapy, have altered the landscape of PBC management. To learn more about how you can interpret emerging clinical trial data, here are our answers to select learner questions from our recent satellite symposium, Raising the Bar: Innovations in PBC Care. 

Is one peroxisome proliferator-activated receptor (PPAR) agonist better than the other for pruritus or fatigue? How do you use clinical trial data to inform decision-making in the real world? 

Aparna Goel, MD:
I think we have a lot to learn still with these drugs, and decision-making will become easier as we get more real-world data. Regarding the pruritus and fatigue outcomes, these were secondary or exploratory endpoints of the phase III clinical trials. The way I see it, what is being reported is what was interesting in the studies, even if it was not the primary outcome.

The real-world significance of these data remains to be determined. As more patients are treated with the new PPARs and as these patients are followed in the open-label extensions, we will learn more details about how the extrahepatic manifestations are affected by the medications.

Are you confident about the symptom benefit of treatment with PPAR agonists for pruritus and fatigue?

Christopher L. Bowlus, MD:
Regarding pruritus, I think it is important to take into consideration how the symptom benefit is being measured. The numeric rating scale used in these clinical trials is nice because it is a single value that is easy to do statistics with, but it does not really capture the full extent of how pruritus symptoms can affect quality of life.

I think that, in clinical practice, the important thing is to talk to your patients to see how they are faring on treatment. All that being said, I think that, as a class, I can pretty confidently say that PPAR agonists improve itch.  

Aparna Goel, MD:
Anecdotally, I have seen patients who are receiving a PPAR agonist and have improved itch. One of the other ways I have assessed the impact of PPAR agonists on itch is seeing whether patients can discontinue other antipruritic medications after initiating treatment. Some patients in my practice are able to discontinue cholestyramine, sertraline, and gabapentin because their pruritus is controlled.

Christopher L. Bowlus, MD:
I think what will really be interesting going forward is determining their impact on fatigue in a real-world setting. I think that would be practice-changing, because right now, that is the most challenging symptom to treat.

Although itch is challenging, there are some antipruritic agents to offer. But for fatigue we do not have much to offer other than tips for lifestyle changes. It is unsatisfying to not be able to help patients beyond that. So, if there is really an effect on fatigue, I think that will be a real improvement in PBC care.

Is ursodeoxycholic acid (UDCA) plus a PPAR agonist plus obeticholic acid (OCA) an option for triple therapy in the real world?

Aliya Gulamhusein, MD, MPH, FRCPC:
In Canada, we still have access to OCA, so I use triple therapy when I feel it is indicated. My collaborators and I recently published a series of 50 patient cases showing that triple therapy led to improvement in alkaline phosphatase, including normalization in almost a third of patients at 6 months. Approximately 64% of individuals also reported reductions in pruritus intensity with triple therapy.

That said, the use of triple therapy is generally limited to patients who are truly high risk—that is, typically younger individuals with persistent elevations in liver tests, particularly ALP levels >200 IU/L, despite an initial second-line therapy. So, if you have access to these medications and the patient is high risk, I think triple therapy is a reasonable option, provided you are comfortable with its use and have sufficient experience managing these patients.

Fibrates are available in many countries at a much more affordable price than other second-line treatment options for PBC. How do you feel about use of an off-label option in such a context?

Christopher L. Bowlus, MD:
Historically, healthcare professionals (HCPs) used fibrates off label largely because of the lack of other options. But now that there are other drugs that have been demonstrated to be safe and effective in clinical trials (ie, seladelpar and elafibranor), I would use those instead. 

I am a bit concerned about the potential for hepatotoxicity with fibrates. It seems to be more pronounced in cholestatic diseases. In the BEZURSO study, the number of adverse events was relatively high with bezafibrate and UDCA combination therapy. So I think HCPs need to be careful with dosing if considering off-label use of these drugs when using them in PBC.

Aparna Goel, MD:
I will continue patients on fenofibrate if they have been on it for a long time, are doing well, and prefer not to switch. But for others who do not have disease control, or those who are newly initiating second-line therapy, I will not choose fenofibrate over 2 potentially equally—if not more—effective therapies that are now approved by the FDA.

Aliya Gulamhusein, MD, MPH, FRCPC:
I also worry a little bit about toxicity with off-label use of fibrates. I rarely use a full dose of bezafibrate to start. In general, I start with 400 mg of bezafibrate every other day, and if patients show treatment response, then I continue that dose. If they do not, I slowly up titrate and monitor.

Your Thoughts
How would you approach the treatment of a patient with biochemical response to UDCA but persistent itch? Leave a comment to join the discussion!

Continue