Advances in Treatment of Primary Biliary Cholangitis (PBC) - Episode 15

Switching Treatment in PBC

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Experts in hepatology comment on how long they keep a patient with PBC on first-line treatment before deciding to switch to another therapy.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Ed, we have all the trials for second-line treatment that would require the patient to be on a stable dose of ursodiol for a year before you can consider second-line treatment. What is your practice? Do you start the patient on second-line treatment and then wait a year before you decide that they need to have fenofibrate added or something else?

Edward Mena, MD: It would depend on the staging of their disease. If I felt that they had a significant amount of fibrosis, especially on a FibroScan showing greater than 10 kPa, I’d probably start them on a third-line agent in this case because they’re on ursodiol or obeticholic acid, probably in 6 months.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: So, 6 months for you if they have advanced-stage disease. David?

David Victor III, MD: I’m similar, except there’s one other group of patients. With someone whose FibroScan value has gotten worse in a year or in a short order, I will be more apt to add a third agent or increase obeticholic acid to 10, even if they do have some mild pruritus, in hopes that you can stop the progression of disease. Though the 6-month intervals likely will be adequate moving forward, but all the data are based on a year, so that’s the standard. I am a little more aggressive in adding a second or third agent based on their stage of disease.

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

Steven Flamm, MD, FAASLD, FACG: Same for me. As time goes on, we are becoming more aggressive and looking at changing our regimens or adding to the medical regimens earlier. Yes, the way the POISE trial was designed was somebody not responding or not having an optimal response to ursodiol after 12 months of therapy. Though when you look back at the data, we’re starting to see that you can tell at an earlier time point whether patients are or are not responding well to therapy and you don’t always have to wait 12 or more months. There are more data coming out for that.

You can tell whether obeticholic acid is working very early on, within 3 months. You don’t have to wait long periods of time to see whether these products work in primary biliary cholangitis. Keeping in mind that we really want to drive down the alkaline phosphatase and total bilirubin levels in these patients, it’s better for us to maintain an aggressive approach and shorten those time points a little when we decide to add additional therapies.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Do you wait 6 months?

Steven Flamm, MD, FAASLD, FACG: Yes, 6 months.

Sonal Kumar, MD, MPH: I usually wait 6 months and then start having discussions with the patient about starting second-line therapy. Sometimes we’re prohibited by insurance approval for getting access to drugs, but at the very least, I can start those discussions. This 1-year timeline has been based on a lot of these clinical trial results, but we know by 6 months whether or not a patient is going to respond to therapy.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I’m in the same camp. There’s a paper, published in Liver International, from the Global PBC Study Group showing that if your alkaline phosphatase level at 6 months is greater than 1.9 times the upper limit of normal, those patients are very unlikely to reach the POISE criteria of less than 1.67. So, starting alkaline phosphatase is a good point, and then considering the stage of the disease, which is important.

Transcript edited for clarity