Unmet Needs in the Treatment of PBC

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: We’re comingto the end of this discussion, but I want to talk about unmet needs in PBC [primary biliary cholangitis]. What are some unmet needs? I’m going to have everyone comment, but I’m going to start with you, David.

David Victor III, MD: This was a lead-in to say that transplantation for patients with PBC is an unmet need. They’re not well served by our current allocation system, and I’ve implored some of our UNOS [United Network for Organ Sharing] colleagues to consider itching in the malignant, life-altering aspect of pruritis to be something that we incentivize for transplant. Transplant is supposed to make your life longer and better, and many of these patients with recalcitrant pruritus from PBC deserve quality therapy. That’s where I see the biggest unmet need. I don’t think we do great in our transplant world. That’s a bigger question to answer. I’m hopeful that these new therapies and some of the emerging therapies may be able to treat some of our patients who aren’t candidates for obeticholic acid or second-line therapy as we try to prevent them from progressing to such a stage.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s a good point. There’s concern about patients who have decompensated liver disease. Obviously, they can’t receive obeticholic acid. With fibrates, there are some concerns and warnings about liver or kidney toxicity. Clearly, that’s the population where there’s a big need. I’ve had 3 patients in my career who I was able to get either prior to MELD [model for end-stage liver disease] and requiring exception points or during MELD with exception points for refractory life-threatening pruritis, 2 of whom were considering suicide. Those patients would not be eligible for exception points in this era. It’s uncommon, but it’s a huge unmet need. Ed, what do you think are the unmet needs in this disease?

Edward Mena, MD: Something we looked at in our clinic is ethnic disparities in PBC. We found that our Latino population who had PBC came at a much later stage of disease. Most of them have cirrhosis. David, you mentioned patients with PBC languishing in clinics. Increasing awareness of PBC and screening using the antimitochondrial antibody in certain ethnic groups or communities would be of value.

Steven Flamm, MD, FAASLD, FACG: Like many things in liver disease, Kris, they’re all out of unmet needs. First, there’s an unmet need regarding the education of practitioners in how to diagnose this early. There’s an unmet need in terms of having more effective primary therapy in the first place for patients with PBC. There’s an unmet need for the treatment of the profound fatigue that some patients have with this disease. Even if they don’t have cirrhosis, it’s a major quality-of-life issue for them. There’s an unmet medical need for the pruritis. The pruritis doesn’t always correlate with the advance, with the stage of the disease. That’s also a misunderstanding. Patients can have moderate pruritis, which does affect their quality of life, but it’s not enough to need a transplant, and their liver disease isn’t so advanced. We know we could do better with therapy. So, there are a lot of unmet needs in PBC.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I agree, and your point about pruritis and symptoms not being correlated with disease severity is important to recognize. Some patients, as they start having more symptoms, are petrified, and their fatigue is getting worse. They think they need to get on a liver transplant list.

Steven Flamm, MD, FAASLD, FACG: For patients with PBC, 1 of the extrahepatic manifestations is they can have very profound and aggressive osteoporosis. The guidance documents are clear that patients should have periodic bone densitometry when they have PBC. This, too, doesn’t correlate necessarily with the stage of their liver disease, and you can’t wait until patients are having spontaneous pathological fractures to identify this. The audience should also know in a patient with PBC that they are or should be recommending periodic bone densitometry to look for osteoporosis or even osteopenia.

David Victor III, MD: At a minimum, your patient with PBC who comes into the office every 6 months or 1 year should have a vitamin D test with their standard labs. That’s a guidance, but it’s often not done. We added it to our standard order set for patients with cholestatic liver disease, so other providers would do it. That’s the best and easiest screening tool to identify higher-risk patients.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s an excellent point. Fractal vitamin deficiency isn’t necessarily seen only in patients with jaundice, so we do that routinely when we first see the patient. Sonal, you get the last word on unmet needs for education and for patients or clinicians.

Sonal Kumar, MD, MPH: I’ll piggyback on what Steve said. As physicians, we focus on normalization of the alkalis or goals of preventing and disease prevention, which are understandable and obviously important. But from a patient perspective, what affects their day to day is their quality of life. If we can improve that, in combination with these new therapies, that will prevent disease progression. That will be huge.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s great. That hour and a half went by fast. I appreciate the chance to share thoughts and clinical experience. Thanks to all of you for this rich and informative discussion. Before we conclude, I’d like to get some final thoughts. Everybody gets 30 seconds. Let’s start with you, Steve.

Steven Flamm, MD, FAASLD, FACG: The practitioners in the audience should understand that although this is an uncommon disease, it’s not so uncommon that you won’t see it. You will, and you need to know how to diagnose it and be comfortable about the diagnosis. Be aggressive in your therapy, even in patients who are asymptomatic. Follow their fibrosis scores, and don’t forget these extrahepatic manifestations, which are more prominent than any of the others in liver disease: osteoporosis, hyperlipidemia, pruritis. Become comfortable with it, understand it, and follow the patients aggressively because you’ll help them.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Sonal?

Sonal Kumar, MD, MPH: Steve summed it up well. Disease awareness is a big deal in PBC. Although this is a rare disease, it’s not something you’ll see once in your lifetime or never see. It’s important for practitioners to be aware that this disease exists and recognize that it’s an exciting time for patients with PBC. We have good therapies already in existence but even more exciting therapies in development.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Ed?

Edward Mena, MD: I agree with what everyone said. But let’s not let these patients languish in our clinics. Let’s follow that alkaline phosphatase, and let’s get that alkaline phosphatase to normal.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: David?

David Victor III, MD: Having the last name Victor puts me at the end of this. Our panelists have hit on all the issues. To the providers and practitioners watching this, go through your clinic and make sure you’ve optimized the patients you have to make sure they don’t see me for transplant.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s very well summed up. Thank you again. To our viewing audience, I hope this Peer Exchange discussion was useful and informative. If you enjoyed the content, please subscribe to our e-newsletters to receive Peer Exchanges and other great content in yourin-box.

Transcript edited for clarity