Use of Obeticholic Acid (OCA) in PBC

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I think we’ve made a few important points. I like the fact that you brought up that Urso can be expensive and can be difficult. About 10% of patients, we think, are intolerant to Urso and experience weight gain, hair loss, and other symptoms. For those patients, do we have an option, Steve, in terms of the data with monotherapy with OCA in patients who are intolerant to Urso?

Steven Flamm, MD, FAASLD, FACG: That’s a great question, Kris. The POISE study, which was the pivotal trial that led to the approval of obeticholic acid for patients who were either not responding well to or intolerant of Urso, did have a group of patients who were intolerant to Urso and thus were not on Urso, so they did receive obeticholic acid monotherapy. There was also a study before that using obeticholic acid monotherapy for patients with PBC [primary biliary cholangitis]. Both showed the same thing, that you did have very good efficacy and similar tolerability in that patient population. So, if a patient isn’t tolerant to Urso and can’t take it, I use obeticholic acid monotherapy for patients with primary biliary cholangitis.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Is that true for you, Sonal? What’s your experience with using obeticholic acid as monotherapy?

Sonal Kumar, MD, MPH: Same thing. There are very few, and maybe we have just a couple of patients who either can’t get Urso or can’t tolerate it, but in those patients I will use obeticholic acid as monotherapy.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That’s a good point. Obeticholic acid is effective as monotherapy for Urso-intolerant patients. In fact, you get pretty close to the same response that you do with second-line therapy with obeticholic acid, so that’s important to keep in mind for our Urso-intolerant patients. I’ll say a few words about the long-term results with obeticholic acid. We now have 5-year open-label safety extension data from the POISE long-term safety extension study. We know in these patients that the majority of the patients, in fact, almost all the patients, maintain their alkaline phosphatase at goal, which is less than 1.67 times upper limit normal with maintaining a normal bilirubin. The more impressive results with regard to outcomes show that you have a significant reduction in clinical events, which is ultimately, of course, what we want to reduce. As you mentioned, we want to avoid liver transplantation. We want to tell these patients they can achieve normal life expectancy. We have data from the long-term POISE extension study about how the risk of outcomes is dramatically reduced, and the hazard ratio for events is about 60% or greater reduced, so I think that’s encouraging and really gives us strong evidence that we can potentially use obeticholic acid and actually reduce those adverse outcomes.

Transcript edited for clarity