Managing OCA-Induced Pruritis in PBC

EP: 1.Overview of Primary Biliary Cholangitis (PBC)

EP: 2.Classification of PBC

EP: 3.Triggers and Risk Factors of PBC

EP: 4.Disease Progression of PBC

EP: 5.Impact of PBC on Quality of Life

EP: 6.Diagnosis of PBC

EP: 7.Care Management in PBC

EP: 8.Guidelines and Risk Stratification of PBC

EP: 9.Treatment Selection for Patients With PBC

EP: 10.Current Treatments for PBC

EP: 11.Use of Obeticholic Acid (OCA) in PBC

EP: 12.Safety Considerations With OCA in PBC

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EP: 13.Managing OCA-Induced Pruritis in PBC

EP: 14.Real-World Data on OCA in PBC

EP: 15.Switching Treatment in PBC

EP: 16.Triple Therapy in PBC

EP: 17.Emerging Treatment Options in PBC

EP: 18.Unmet Needs in the Treatment of PBC

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: What are the main adverse effects of obeticholic acid and how do we manage them?I will start with you, Sonal.

Sonal Kumar, MD, MPH: Pruritus is probably the No. 1 adverse effect that I’m sure we’ve all encountered in our patients. It’s a little tough to manage pruritus in a patient population that already may have baseline pruritus, but I usually start with cholestyramine. Well, first I start with lifestyle changes to really delve into. Are there some low-hanging fruit where they can make some changes? Then, if it requires pharmacotherapy, I’ll start with cholestyramine. Though, I have to say it doesn’t work very well and it’s really difficult to take with other medications.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Ed, any tips on your stepwise approach to managing pruritus?

Edward Mena, MD: I still start off with cholestyramine. The one thing with cholestyramine that you have to remember is it can absorb other medications, so I tell them not to take other medications either 4 hours before or 4 hours after taking the cholestyramine. I’ve also used other medications such as rifampin. Everybody always worries about the hepatoxicity with rifampin, but I haven’t found that much to be the case. I think rifampin does help our patients with itching. To a lesser extent, I’ve used Zoloft. I haven’t found Zoloft to help very much with their itching, but it is kind of recommended on the guidelines. Those are the 3 that I typically use.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: Steve, you take care of a lot of patients with PBC [primary biliary cholangitis], and you lecture others about how to manage treatment with obeticholic acid and just managing the symptoms. Any pearls from your standpoint? What about naltrexone or rifampicin, do you use those?

Steven Flamm, MD, FAASLD, FACG: I do. Well, first, antihistamines, everybody starts with antihistamines. I have not had luck with antihistamines. Keep in mind, though, that many patients have insomnia, or the itching is worse at night. So antihistamines may be helpful for their sedative effects for sleep but as far as the itching part, I have very rarely had a favorable outcome. I start with cholestyramine. I have a little better luck, I think, than Sonal does. I’m going to say maybe 50% of patients have some benefit…with it. I use rifampin more liberally. I know you and I have had this discussion before, and you found a lot of hepatotoxicity with it…. I haven’t. I’ve used it dozens and dozens and dozens of times, and I think I’ve had 1 patient that I recall had liver hepatotoxicity from rifampin. Though, if a provider does use it, they need to keep that in mind. Watch the liver panel. If patients have increase in jaundice at all when they’re on rifampicin, stop the drug. Don’t forget that it is a possible hepatotoxicity. Though, of all the therapies for pruritus in cholestatic liver disease, to me, rifampicin is the best. I have luck in probably 75% to 80% of patients.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I must say Steve is right. I’ve anecdotally been concerned about using rifampin because I had patients who developed hepatotoxicity and therefore, I’m afraid to use it, but it does work for some patients. I think the key is if you’re going to use obeticholic acid, first recognize that the vast majority of our patients with PBC will have pruritus at some point. So that is not a reason to not consider using obeticholic acid. Also, as you mentioned, that if you start at 5 mg and go to 10 as opposed to starting at 10, what the POISE trial showed was that discontinuation due to itching is only seen in 1% versus 10%. So patients do acclimate to the itching, and in my experience, it’s really in the first few weeks that you need to really counsel the patient about skin hygiene: using an aloe-based, not a water-based, lotion; keeping the nails short; avoiding hot showers; and that kind of thing. It is just really important to emphasize. Most patients can get through it. Any additional comments about managing pruritus? I think the other drug that’s often mentioned is naltrexone. Have any of you used it? I’ve only used it once. The patient didn’t tolerate it that well, but it is in the kind of stepwise approach.

David Victor III, MD: I’ve used it once, and it was moderately effective but financially unpalatable to the patient…. I think you hit on the most important part, is that when you initiate obeticholic acid, you are changing the bile acid milieu. If the patient is used to itching from the PBC they’ve had for many, many years, you’re changing their itch. The noise or the sound is going to be different. If you think of it like a candle, when you change the scent of a candle in your house, it’s very potent the first few hours and then you kind of get used to it. So you prepare your patient for, “You are going to itch. It’s going to be different. You will become somewhat used to it and this will be your new itching. It’s not any worse,” and get them on lotion before they start, and make sure that they’re not doing things that will exacerbate their problem. I’ve had a lot of good uptake by telling them that they will have this adverse effect and “Here’s what you do to prevent it from being terrible.” Cutting the fingernails was one I learned by mistake, by not telling people to cut their fingernails and having significant excoriations that, once started, are almost impossible to get the patient back to stable. I really think that setting expectations with patients that they will have symptoms and telling them ways to prevent the symptoms from being life-altering, and making sure that they sleep are important. I’ve had pretty good uptake. I’ve only had 1 patient stop medicine for itching in all of the dozens of patients I’ve treated with obeticholic acid.

Kris Kowdley, MD, FACP, FACG, AGAF, FAASLD: I think those are good practical pearls. Regarding cholestyramine, I would say certainly my mentor, Marshall Kaplan, MD, always told me that if a patient is itching badly enough, they won’t complain about the cholestyramine. The ones who aren’t itching that much that you put on cholestyramine are the ones who will complain of the adverse effects. I think we need to use cholestyramine without fear, encourage our patients to stay on it. And as you alluded to, Steve, there are new therapies now in clinical trials such as IBAT inhibitors that promise additional relief for our patients.

Transcript edited for clarity