In this video, Dr Bonder discusses promising developments in medical therapies for patients with primary biliary cholangitis that were revealed at the recent virtual annual meeting of the American Association for the Study of Liver Diseases.

Alan Bonder, MD, is medical director of liver transplantation at Beth Israel Deaconess Medical Center in Boston and assistant professor of medicine at Harvard Medical School.

TRANSCRIPT

Good morning. I'm Alan Bonder. I'm the Medical Director of Liver Transplantation at Beth Israel Deaconess Medical Center. I'll be excited to talk about highlights of primary biliary cholangitis from AASLD. I will emphasize that patients with primary biliary cholangitis (PBC), up to 2016, had no other options except ursodeoxycholic acid.

As everyone remember, in 2016, based on the POISE trial published in the New England Journal of Medicine, we got a second medication approved by the FDA, obeticholic acid, which helps patients who did not respond to conventional therapy.

After that, we had no more approvals from the FDA to treat patients with primary biliary cholangitis. That's how important is this as the advances in this disease over the last couple of years is being huge. So far, we have 4 new clinical trials that were discussed in detail at AASLD. I will explain the medications, the mechanism of actions, and their outcomes.

First, we're going to talk about the PPAR agonists, the peroxisome proliferator-activated receptor agonists. To help people remember, there is alpha, there is gamma, and there's delta receptors. In this case, we will talk about two medications that were discussed in detail at the liver meeting.

The first one is the saroglitazar. Saroglitazar is a PPAR agonist alpha and gamma. This was a randomized controlled trial named the EPICS, in which patients were randomized to placebo versus medications. At the end of the trial, which was a phase 2 trial, they showed that patients who were given saroglitazar had better outcomes, meaning that the patient had improvement in their alkaline phosphatase and their markers of inflammation at the end of treatment.

The second clinical trial that was very interesting -- it was discussed by Gideon Hirschfield -- was the seladelpar, which was the ENHANCE study. Seladelpar is a PPAR delta agonist.

In this 52-week randomized controlled trial, it showed that even at 3 months, patients who were given the medication had improvement of their alkaline phosphatase and also improvement in their management of the symptoms, basically managing pruritus.

The other two clinical trials that were also done, they were the EDP-305, which is an FXR [farnesoid X receptor] agonist, which is called the INTREPID study. In this study, patients were randomized to 1 milligram, 2.5, and 10 milligrams. At the end of the clinical trial, patients who received the medication had an improvement on their markers of inflammation, as well as liver function tests.

Finally, another medication which has a bile acid transporter called linerixibat, which is the GLIMMER trial, which also showed that patients who were given the medication improved in their markers of inflammation, as well as liver function tests.

As I discussed before, these 4 clinical trials are very exciting. There are a lot of promising new medications and also new treatments for patients who do not respond to conventional therapy.

Going back to the other trials that were mentioned in AASLD, I want to mention one of the trials that was done as an oral presentation about the treatment of severe fatigue in patients with PBC.

As people know, fatigue is one of the main symptoms that goes along with the disease. We currently don't have a good treatment for this. Even all the disease-modifying medications in all the clinical trials, none of them use fatigue as part of their outcomes.

In this clinical trial, in the UK, they used this home-based exercise for a total of 12 weeks. They included 25 patients. They had phone conversations. They had 6-week and 12-week follow-up. After 12 weeks, patients who had this home-based exercise regimen improved in their quality of life and improved in their fatigue at the end of the treatment.

This is very exciting. This is also very important so we can recommend patients in clinic they should exercise on a regular basis to try to improve in their fatigue.

Another clinical trial was the increased incidence of anxiety and depression in patients with PBC. Again, we are clinicians. We are very busy talking about disease-modifying medications and trying to focus a little bit on the pruritus part, but we also forget about the psychosocial part of the disease. It is very important to ask about anxiety and depression.

In this clinical trial that was also done on a large dataset, it was found that patients with PBC are at increased risk for depression and anxiety. The treatment for depression and anxiety is very important in the clinical outcomes and in quality of life in patients with PBC.

Finally, I want to mention the obeticholic acid. Over the last couple of years, since 2016 with the publication in the New England Journal of Medicine, with all the new medications and the side effects that this medication has, it lost a little bit on popularity. Two clinical trials showed the long-term efficiency of obeticholic acid.

The first one showed that in a biochemical perspective, meaning liver test, as well as inflammation, patients with PBC improved at the end of treatment. The most striking data about the obeticholic acid was the 5-year long-term study. This is published by the PBC GLOBE.

The most important and the most striking information about this is the changes in biochemical parameters that the POISE trial reported does not fully capture the benefits of obeticholic acid. Even after treatment of 5 years, we can see that patients with PBC who did not respond to conventional therapy are now responding to obeticholic acid despite the side effects such as pruritus.

This was a very exciting liver meeting in the PBC and cholestatic world. As we can see, we have four new medications coming in in phase 2 and phase 3 clinical trials.

Also, we have reassurance that the medications that we had before are medications that can work. The medications can treat their disease, and that can make sure that they can improve their liver outcomes from biochemical parameters.

Again, it's very important to understand that also PBC carries other psychosocial problems such as anxiety and depression. Finally, we should, clinicians, put an effort to try to look for other things, and specifically ask patients for psychosocial conditions such as anxiety and depression to see if we can offer treatments and get their quality of life improved.

Again, thank you so much for listening to me. I hope this video helps to get your highlights and updates about primary biliary cholangitis from AASLD and hope to see you soon.