Drs Kris Kowdley, Steven Flamm, Sonal Kumar, Edward Mena, and David Victor discuss their approach to initiating treatment of PBC as well as managing this chronic condition.
Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Let's move on and talk about current and emerging treatment options. I'm going to kick this off by talking about how to control symptoms. We want to improve patients’ quality of life while slowing disease progression. We want to reassure the patient, depending on what risk bracket they are in, that they may not be at risk for progression of liver disease or need liver transplantation or liver-related death. Those are our sort of 3 major buckets since we're not so much able to treat the extrahepatic symptoms, but obviously we want to relieve pruritus, improve fatigue, for which we have limited options, and slow disease progression, for which we have quite a lot of options. Given that management of PBC is lifelong, Ed, Steve, and Sonal, David, everyone, what are your considerations in choosing a treatment? I will start with you, Steve.
Steven Flamm, MD, FAASLD, FACG: Well, Urso [ursodiol] was first approved for treatment of PBC as a primary indication more than 20 years ago. It established a first-line therapy. In all patients that have primary biliary cholangitis, I use Urso. We need to be careful to dose it correctly, 13 to 15 milligrams per kilogram per day and divided dosages. Sometimes, I see patients that are being underdosed, so I correct that when they come in on the drug already. Then, you can't be lulled into a sense of security with this disease, Kris. This is a problem I find with a lot of practitioners. Many patients are asymptomatic. They may not have advanced fibrosis, so they start them on Urso and they kind of just swallow them periodically. You have to take it seriously because diagnosing this early and treating it aggressively earlier will help long-term outcomes. So, you need to follow these patients and you need to watch laboratories such as alkaline phosphatase and bilirubin and aggressively treat them to, again, improve their long-term outcomes. Ursodeoxycholic acid is what I start with.
David Victor III, MD: I follow the same pathway, but I talk to the patients about maintaining inertia in their own disease, and that this is going to be lifelong. Oftentimes the worst-case scenario, as I'm a transplant hepatologist, is to meet a patient at cirrhosis, to meet them when their disease has been managed the same way because we've had limited options until recently, and now they've slowly progressed to cirrhosis. I think the new guidance and the importance of elastography and monitoring therapy for making it the best we can as we have newer and newer options is really important. For our providers in primary care and GI, these patients aren't going to have symptoms that show you slow progression. You have to look, and maintaining that idea that there is more to do than just kind of wave every 6 months or a year to these patients is important. I really try to keep that inertia and reinvigorate each PBC patient that comes to my office to remind them that this is something that they need to work on themselves and maintain as an important part of their life, more so than just taking their medicine.
Edward Mena, MD: I'm glad you mentioned that this is a lifelong disease. Just this past week I had a patient that I prescribed ursodiol to. She comes 3 months later and her alk phos hadn't budged and I go, ‘Did you take your medication?’ She goes, ‘Yes, of course, Dr Mena, I took it. I only took it for a month and then I didn't get the refill again because I thought I was done.’ I think educating them on the lifelong therapy for ursodiol twice a day is very important. Steve, I'm glad you mentioned that it's 13 to 15 milligrams per kilogram per day because I was remembering when I was a fellow, 20 years ago, I think we were recommending 10 to 15 milligrams per kilogram per day. So, you can kind of see how sometimes patients come underdosed with the proper dose of ursodiol.
I think the future is really exciting now that we have second-line therapies if our patients can't or don't get their goals of their alkaline phosphatase. I think our goals, like we said earlier, is normalization of alk phos and getting that bilirubin down. So, the therapies that we have today, which would be obeticholic acid and possible fenofibrates, and hopeful future therapies make the halt of this disease progression very likely in the future.
Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Sonal, what are your considerations in both choosing treatment and deciding to start treatment? What are your treatment goals really?
Sonal Kumar, MD, MPH: I think I agree with what everyone is saying that it's really important that we engage the patient and have them really understand what the disease is about. This is not a 1-month supply of medications and then you're done. This is not something that if you don't have symptoms, you can't still have disease progression. My goal is pretty consistent with the Global PBC Study Group goals of normalization of alk phos and bilirubin being less than 0.6. If they don't meet those goals in 6 to 12 months, that's when I start thinking about second-line therapy. I tell patients actually from the beginning that these are our goals, and we will monitor you and after this amount of time, that's when we will consider additive therapy.
Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: That's great. So, I think we're all aligned in terms of our treatment goals. Bringing the alkaline phosphatase as low as possible and trying to maintain the bilirubin in normal range, and ideally also achieve normalization of liver enzymes, is very important. Certainly, the way I'm thinking about PBC, is we're really oriented towards trying to achieve a deep remission, biochemical remission, et cetera.
Transcript edited for clarity