John Botson, MD, RPh, CCD: Pegloticase Efficacy and Safety in Patients With Gout

This week, Rheumatology Network sat down with John Botson, MD, RPh, CCD, to discuss 2 studies covered in EULAR 2021: Pegloticase Efficacy and Safety in Kidney Transplant Recipients and Demographics, Comorbidities, and Renal Function of Uncontrolled Gout Patients Who Received Pegloticase. Botson is the Rheumatology Director at Orthopedic Physicians Alaska. He explains why patients with uncontrolled gout are significantly burdened with systemic co-morbid disease, why gout is more prevalent and severe in patients who have received kidney transplants, and why such few studies have been published on the use of pegloticase in organ transplant patients.

Rheumatology Network: Hi, Dr Botson. Thank you for joining me today.

John Botson, MD, RPh, CCD: Hello.

RN: What sparked your interest in examining pegloticase efficacy and safety in kidney transplant patients?

JB: Well, pegloticase has been a medication that we've been using now for quite a few years, more recently in the last 2 to 3, for these patients with chronic refractory gout. But 1 of the populations that really was pretty under-studied was those patients in kidney transplant. And as most of us know, the kidney is how the uric acid is processed and how its eliminated. And when you start to talk about the kidney transplant patients, not only do they have some compromised renal function, they also have medications that make them more likely to have higher gas levels and gout.

RN: Why do you believe such few studies have been published for the use of pegloticase in organ transplant patients on immunosuppressive medications, and that phase 3 trials excluded this patient population?

JB: Well, I think it's a small population first, that is hard to include in clinical trials. It's also much different than the population that we typically deal with. Once you have a patient that has an organ transplant, particularly like a kidney transplant, it really sort of excludes a lot of other providers that take care of these patients. It's a pretty specialized group of nephrologists, usually and rheumatologists that care for these patients. And I think when people are setting up normal clinical trials, they're trying to keep the population pretty narrow, so that they can look at primarily the most common presentations. And so usually, it's a bad idea to set up a study where you include a lot of the outliers, if you will, and that would be the case with transplant patients.

RN: Why is gout more prevalent and severe in patients who have received kidney transplants?

JB: Well, again, like I mentioned before, a lot of it has to do with just the decreased renal function. Obviously, they're better renal function than if they were on say dialysis. But also, the medications that we use, particularly to help with anti-rejection of the organ of the kidney, lead to elevated uric acid levels. And most nephrologists know that a lot of the patients in their panel, whether they actually complain about a joint pain, have high uric acid levels. And so, a number of these patients, statistically, somewhere around 13% of these patients on transplant, will develop gout eventually. So, these are the populations we need to really focus on.

RN: What is the clinical significance of this study?

JB: The clinical significance of this study is this is really the first time we've looked at a population with renal transplant. We're always a little bit nervous about this population. Because of the medications that we use. We're worried about toxicities. Like you had suggested earlier, we just don't know a lot of these data when these medications are approved. And so, the significance of this finding is, is that we found that really pegloticase can be used safely in these patients with transplants that have gout and really it doesn't compromise their kidney function more despite using these medications.

RN: Did the results of the study surprise you?

JB: I've been using pegloticase for quite a while and truthfully, it didn't. It was one of those studies that I'm glad the data is finally there to support what most of us believed and when we've had other patients that have had, you know, poor kidney function before transplant, even stage 3, 4, or 5 kidney disease, the medication works. So, most of us believe that there wouldn't be an issue with a patient that technically has a better kidney function with the transplant. The big question was whether these other medications, the immunomodulators, the things that we're using for the transplant itself would affect the way the medication work with pegloticase. And, in fact, it seemed to be very well tolerated, and it seemed to work well as we would expect in other patients.

RN: Moving on to the second study, why do you believe patients with uncontrolled gout are significantly burdened with systemic comorbid disease?

JB: Well, what we're finding in what has come up over the last few years, maybe even as far back as a decade is that chronic inflammation is a bad thing for systemic diseases. And so, whether that chronic inflammation comes from rheumatoid arthritis, whether it comes from cardiovascular disease, because of high cholesterol and other comorbidities, what we're finding is that having a high serum uric acid is very inflammatory. And it's a systemic process. It's not just in a toe or in a finger. And so, as we've started to look at these patients, more of those patients that really can't get their gout in control have more chronic systemic inflammation that might be going on for decades. And when you will start to look at that, like we would kind of predict the metabolic syndrome becomes more prevalent in these patients. And that's those patients that have chronic kidney disease, hypertension, type 2 diabetes, cardiovascular disease, all of these things that we kind of forget about, it could be related to gout. And that's, that's what's coming to light with the studies.

RN: Can you briefly summarize the results of this study?

JB: Basically, this was a claims database study. So, this was the first time we really looked at these patients. This was all US claims database, and basically, we search the database for patients that that were on medications, like pegloticase, as well as immunomodulators. And we tried to see how they did and basically, what we're looking at is just what we suggested was the comorbidities, to see if that had a role here. And, and looking at whether patients that had some chronic kidney disease would actually do better or worse. And basically, what we found is as almost 1500 patients, who were treated with pegloticase, and they did have those comorbidities that we just mentioned: the kidney disease, hypertension, type 2 diabetes, and cardiovascular disease. But I think what was interesting to me was that when we started looking at those patients that were able to complete a full course of treatment. And so, by that we mean that the patient was in the database, received the pegloticase and then remained in the database for 2 years after that first treatment. And what we found there is that 83% of the patients, they had a stable or improved kidney disease after receiving the payloader case, and 89% of those patients that already had stage 3 through 5 chronic kidney disease, also, were stable, are approved. So that was a pretty amazing timing to sort of support some of our thoughts.

RN: Why do you believe that gout has been largely neglected in regard to medical studies, including therapies with pegloticase?

JB: Yeah, that's a great question. And it always comes up because gout, as you know, has been around since medieval times. Gout has, I think, not been studied until more recently, because I think it was looked at as a disease of gluttony, it's looked at as a disease of patient blame. And that's not the case. A lot of this is genetic. A lot of this has nothing to do with the person's diet. And we're starting to see now that these this is one of those diseases, like hypertension or high cholesterol, that we really need to manage. And so now that we have powerful medicines, like pegloticase, that we can actually get patients to goal that we can actually take away tophaceous deposits that have come up over years, we now have some options for these patients. And now it's coming more to light that we really need to be more aggressive on these patients.

RN: Do you plan on doing any further research on this particular topic?

JB: I love gout. So, yes, I think it's been super exciting for me. I have been involved since the beginning of the immunomodulation with pegloticase. So, Dr. Jeff Peterson and I actually did the first case series on methotrexate. And so ever since then, it's just been a fantastic whirlwind of studies that we've been able to do. And each of these additional studies that come up, improve the patient experience, you know, improve the patient's outcome. So definitely, I'll be planning on doing some more. And I'm really excited about a couple of the studies that are ongoing now, including the randomized control trial with methotrexate which should really solidify as this one is a blinded trial should really solidify the findings with immunomodulation. And making pegloticase work better for these patients, when we can when we can use it in combination.

RN: Is there anything else that you'd like our audience to know about gout before we wrap up?

JB: Um, well, you know, I think it's still it's still a learning process and is still an educational process for a lot of providers. And this is rheumatologists, as well as primary care providers, as well as podiatrists who are seeing these patients first line, I think it's still an education process to take the blame off of the patients and really put the focus on chronic management of a refractory disease. And I think that would be my take home messages for these patients that are coming in to see their primary care provider. Don't put their gout you know, 5th thing on the list for the day. Let's move that up right behind their diabetes or their hypertension, and really address this and not wait for them just to come in when they have a gout flare. You know, we need to address this upfront. So now that we have medications that we can use, we can keep people from having these chronic conditions and metabolic syndromes get worse.

RN: Well, Dr Botson, thank you so much for speaking with me today. I really appreciate it.

JB: No problem. I'm happy to do it.