Impacting Disease Outcomes and Quality of Life in PBC: Individualizing Treatment Selection and the Role of Novel Therapies

Announcer:
Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.

Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.

Ms. Goacher: 
Hi, everyone. My name is Elizabeth Goacher. I'm here to talk to you on CME by ReachMD. And in this brief lecture, we're going to review best practices for the assessment and management of PBC-related fatigue.

PBC-related fatigue is a separate and significant entity. It is independent of the degree of disease generally. You can measure liver disease by biochemical endpoints like their alkaline phosphatase and bilirubin and radiologic findings, but we know fatigue as well as pruritus, both of these can be independent of that degree of disease. That means we have to use appropriate tools to assess for this. It makes a huge difference in our patients' lives.

In the UK-PBC Consortium, which was over 2,000 patients, they were able to find that the quality of life was significantly reduced in particular in relationship to fatigue. And so up to 35% and 46% of these patients are tired compared to their age-related and sex-matched cohorts, right? Because we're all tired all the time. So, hey, why is PBC more? Is it really more? Yes, it's really more. It's least 2 to 3 or 4 times as high as fatigue scores reported in PBC patients compared to their controls.

And so in association with that fatigue, we see social dysfunction. This was also pulled out of the UK-PBC Consortium. People who are tired start to socially disengage. It's too tiresome to engage with people; they then become more withdrawn. This exacerbates the symptoms of fatigue. It adds to physical inactivity which leads to more fatigue. So these are patients that are experiencing fatigue not just initially, but then exponentially depending on the severity of the fatigue in the first place.

And they also, in the UK-PBC consortium, reported that the number one thing in PBC that was impactful to them, patients report that fatigue is the most impactful symptom to them, above pruritus, above itching. So it's important that we as healthcare providers are really thinking about how we assess this and making sure we're addressing it for patients where we can.

It is difficult to define. We know that the severity of fatigue is unrelated to the severity of the illness itself, so we need to make sure we're using tools that are appropriate to assess it, right? Your bilirubin is not necessarily going to be a good tool to assess your degree of fatigue.

It's also important to make sure that patients understand that. So that fatigue is important because it's important, but it's not necessarily an indicator of their physical debility in terms of likelihood of needing a liver transplant. It's important, I think, you can feel severely fatigued, but you're not headed to a transplant at that same time because you don't meet criteria. So helping patients understand and be reassured that we think it's important but it's not necessarily the thing that's going to cause or be the thing that makes them drive that path to liver transplantation any faster.

Some of the tools that we've seen used to assess fatigue include the PBC-40, which has a fatigue subdomain in it. There are 7 questions there that look at how you define fatigue for yourself. You answer never, rarely, sometimes, most of the time, always to things like I find myself unable to get out of bed. Fatigue interfered with my daily activities. I feel worn out. So these tools are tools you can use. You may not use the whole domain within that PBC-40 tool, but at least using 1 or 2 questions. If you keep those 1 or 2 questions that you use in your practice and ask them all the time, you'll have your own relative perspective for how fatigue is going for your patients.

Other tools include itching tools that reflect on fatigue. So some of the itch assessment tools in PBC-40 talk about did sleep be impacted because of itching, right? So if you're tired because you're not sleeping because you're itching. So making sure that you're looking for contributing factors.

When it comes down to management, that is the first place to start, looking for those contributing factors where you can. So if the itch is from a disease process that you can improve biochemically, hopefully that could improve fatigue, but not always. So making sure that you're thinking about that. Are you treating the itching so they're sleeping better?

Things that can exacerbate underlying fatigue are not your illness itself, the PBC driving fatigue, but maybe fatigue from other illnesses. So treating those comorbidities. So depression is an important one, sleep disturbance for whatever reason, anxiety, mental illness, it's change in weight, if they have a child at home and they're up at night, so treat that sleep disturbance which is driving the fatigue. Do they have sleep apnea, and has that been assessed for?

The other things we do are just to reflect back with patients and treat them with supportive care, to say we understand this is a significant impact in your life. How has it changed? Is it still the same? How is it driving things and keeping you away from what you want to do? How can we help you? Helping people to be pacing in their days, and make sure that they're looking at not doing bursts of energy all at once but using small bits of energy over the course of the day. Or timing, making sure that if you are going to go out and do something, you're looking at the top of the day when your energy stores are going to be higher.

Lastly, we do think about second-line agents that are pulling down data. We're seeing, fortunately, in this world of PBC, these new evolving second-line agents that have really some patient-reported measures that are important, like fatigue and itching, right? And so we were able to see, in the seladelpar, significant changes in fatigue. So depending on the dose, but over 50% in both the 5 to 10 and the higher dose groups of 10 of 64% significant improvements in fatigue, so we're seeing some exciting stuff there.

I hope this has been helpful. Thanks very much for this whirlwind tour, but our time is up. Thanks for spending some time with me with CME on ReachMD. 

Announcer:
You have been listening to CME on ReachMD.  This activity is provided by Prova Education and is part of our MinuteCE curriculum.

To receive your free CME credit, or to download this activity, go to ReachMD.com/Prova. Thank you for listening.