Triple Therapy in PBC

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Speaking of the stage of the disease, that brings us to an interesting discussion among the PBC [primary biliary cholangitis] circles. This is a hot topic, and Ed, you alluded to this in terms of triple therapy. So, have you used triple therapy? When would you use it? If you haven’t used it, when would you consider using it? We have fenofibrate as a guidance recommended treatment off label as well as obeticholic acid approved for second-line treatment, and there are some new agents coming around, which we’ll talk about in a minute.

Edward Mena, MD: I start triple therapy when their alkaline phosphatase level is still elevated, and I like to look at about 1.5 times the upper limit of normal. That’s my cutoff, especially for patients who have a high kilopascal value on FibroScan. I use all 3: ursodiol, obeticholic acid, and fenofibrate and the PPARs [peroxisome proliferator-activated receptors].

David Victor III, MD: I like following Ed because I do what he does most of the time. The only other group is patients who have some pruritus on obeticholic acid of 5 mg. I have added fenofibrate at a low dose to try to accentuate. The group that I’m not sure what to do yet with [is] the patients who are above the upper limit of normal and on 2 agents. Is there benefit as we get more data that normal alkaline phosphatase level is better? I follow the bilirubin level in those groups to decide whether I add a third line or not.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s an interesting approach, using fenofibrate to mitigate the itching. Steve, do you use triple therapy and in what case?

Steven Flamm, MD, FAASLD, FACG: I haven’t yet. The majority of patients respond to ursodiol in the first place. I’ve had very good luck when I use OCA [obeticholic acid] in the patients who did not optimally respond to ursodiol. That’s using, as you’ve worded it, the POISE criteria: alkaline phosphatase level 1.67 or less times the upper limit of normal. I have a lot of patients with levels between the upper limit of normal range and 1.67 whom I have considered responders to dual therapy with ursodiol and OCA. I have not yet considered them nonresponders. I will in the near future as more data appear, but I haven’t had the opportunity to use triple therapy, unless there are data on bezafibrate, which we don’t have in the United States. We have fenofibrate, for which there aren’t the same type of data. So, I haven’t used it yet, but I’d be eager to hear what you’re doing.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I have not used triple therapy in many patients. But…if you have a patient who has not achieved your biochemical end point, especially if they are above 1.5 times the upper limit of normal and have low fibrosis stage, I’m probably going to be using triple therapy more. If they have advanced-stage disease, meaning if they have a liver stiffness result greater than 10 kPa or getting closer to 10 vs 8 [kPa], I’m moving in that direction. Sonal, what about you? Have you used triple therapy in routine clinical practice, and do you think that makes sense?

Sonal Kumar, MD, MPH: I haven’t in my current population. Though I think that’s the wave of the future. As we’re pushing toward normalization of alkaline phosphatase levels, there are going to be a lot more nonresponders out there who would be potentially eligible for third-line treatment. But I have not done that yet in my practice.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: So, there are a lot of new agents.

Edward Mena, MD: Kris, I have a question. In my patient population, which is in Pasadena, California, I have a large Latino population with primary biliary cholangitis. They also have a little overlap with fatty liver disease. So how do you know? Is it failure of the ursodiol or obeticholic acid that’s not causing you to get to goal, or is it a fatty liver problem because we’re not performing biopsy for these patients the majority of the time?

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: It’s a good point. Obviously, along with the entire US population gaining weight and up to 40% of our population having some degree of metabolic fatty liver disease, we’re seeing that the patients with PBC are not immune from this either. If you use transient elastography, the CAP [controlled attenuation parameter] score can be helpful. If it’s over 280 [dB/m or] maybe over 260 [dB/m] and the patient has metabolic features, that’s something you might want to consider. That’s an interesting approach where you might consider triple therapy and other types of things with that. I don’t routinely do liver biopsies for patients with that as a question, but if they have aminotransferase levels that remain elevated as the alkaline phosphatase level is coming down and they have a high CAP score, that’s where you would consider that.

Transcript edited for clarity