The Challenge of Coordinated Gout Treatment

Podcast Transcript

Ian Ponitz
Hello, and welcome to Kicking Gout In The Acid, a podcast from the Gout Education Society. My name is Ian Ponitz, and I’m your host for this series. Kicking Gout In The Acid features conversations between Dr. Larry Edwards, chairman and CEO of the Gout Education Society, and experts on the disease. 

Each episode will dive into important topics that you, the listener, should know about gout. The goal? To feel empowered to get gout under control. 

In this episode, Dr. Edwards is joined by Dr. Tuhina Neogi, professor of medicine at Boston University’s Chobanian & Avedisian School of Medicine, also known as BUSM. She is the endowed Allen S. Cohen Professor of Rheumatology and professor of epidemiology at BU School of Public Health, and chief of rheumatology at Boston Medical Center. Dr. Neogi is also a member of the Gout Education Society’s board of directors. 

Today, Dr. Neogi and Dr. Edwards will discuss the gamut of medical care that gout patients may encounter throughout their journey, issues that can be caused when seeing several disciplines of medicine, and the importance of getting medical professionals on the same page when it comes to managing the disease. 

Dr. Edwards, take it from here. 

Dr. Larry Edwards
Thanks, Ian. I’m delighted to have Dr. Tuhina Neogi on today’s Gout Education Society’s podcast. Dr. Neogi is an internationally recognized expert on many aspects of rheumatology, but especially in the management of gout. Tuhina, can you give our listening audience a bit of your background and how you got interested in gout? 

Dr. Tuhina Neogi
Sure, happy to. Thank you for having me on this podcast. 

I’m originally Canadian. I’m from Toronto, and I did all of my medical training in Toronto. When I was a fellow, I didn’t have too much interest in gout, but Dr. Adel Pham was one of my mentors. He was well known for the allopurinol desensitization protocol, so we got a lot of gout teaching. 

When I completed my fellowship, in order to have a position on the University of Toronto faculty, I needed to get a master’s or PhD, for which I moved to Boston to do that research training. And during that research training, I got a PhD, and as part of my PhD, I had to quickly find a set of thesis dissertation topics, and one of my colleagues, Dr. Yuq Ching Zhang, at the time, was just starting an Internet-based gout study in which we were going to study triggers for gout flares. And it was a very cool study design where each person acts as his or her own control over time, and we studied a whole host of dietary and lifestyle factors as potential triggers for gout flares, and that got me hooked. 

So I like to say that, you know, gout is kind of my hobby topic for my research career, because it was kind of a passion project that I’ve been fortunate to continue working in. 

Dr. Larry Edwards
Yeah. Well, it’s more than a little hobby, because you are certainly an internationally recognized expert in the field, and we’re delighted to have you on today. 

What we’re gonna be discussing is the wide range of physicians and medical professionals who may encounter patients with gout, and how they contribute to the overall care. And we’re also gonna be discussing how being seen by multiple different care providers may impact the overall level of treatment, and how interaction should take place, and unfortunately, how most of the time they don’t. 

So let’s start off just by discussing at the various stages of gout who might first come in contact with somebody who’s suffering from gout. 

Dr. Tuhina Neogi
Yeah. So the vast majority of patients with gout, as you know, are managed in primary care, so that really is the first stop on the patient’s journey. And for some patients, they may not be advised adequately about gout and its consequences, and as a result, may not be started on urate-lowering therapy even if they meet the clinical indications for starting such therapy. 

Some patients may be simply placed on anti-inflammatory suppressive therapy with colchicine just to try to prevent flares or have flares treated as they occur. Unfortunately, that leads to unabated hyperuricemia to continue on for years. And I’m sure you have a much vaster experience than I do of all the patients that come to us after years of such an approach, where they now have bad tophaceous gout with lots of flares or chronic arthritis where the inflammation is there persistently, and are frankly quite upset that their primary care physician allowed this to occur over the years. 

It unfortunately detracts from the trust they have with their primary care physician that if this is what happened with their gout, what else might be happening with their other medical conditions. So that’s the majority of it. I would say that I see some patients coming from nephrology or cardiology, where they happen to either check the urate for some reason, or it’s one of the visits where the patient happens to mention that they need to take NSAIDs because of their gout. 

Dr. Larry Edwards
Yeah, might be on any number of drugs that influence the frequency of gout flares or the ability to take certain compounds. 

In addition to those, Tuhina, a number of patients get their care from urgent care settings or emergency departments. I think I see a lot of patients. On a typical week, I might get called down to the emergency department maybe a half a dozen times to discuss the differential diagnosis of a single inflamed joint. But the thing with urgent care and with emergency departments is that they’re really interested in getting the patient out of their acute facility, and so people can go on for years just following up in that setting and not getting the message. 

Really, what we’re pushing, and what you’ve certainly an expert in, is the treat-to-target approach of taking care of gout, and what you’re describing from a lot of the primary care physicians is really to avoid symptoms with the use of colchicine or nonsteroidals.

Dr. Tuhina Neogi
You made a good point about primary care often using colchicine or NSAIDs on that kind of as-needed basis. 

To me, a perspective we could adopt would be for us as rheumatologists to say to cardiologists, “Oh, your patient has cardiovascular disease. There’s no need to treat the underlying biology of the cardiovascular disease. There’s no need to treat the hypercholesterolemia, the hypertension, the diabetes, obesity, smoking, et cetera. Why don’t you just give them sublingual nitroglycerin, and they can just use it as needed or even, you know, use it chronically to prevent the chest pain? But all you need to do is treat the chest pain, not all of the underlying biology.” 

Or an even perhaps more ridiculous way to drive home the point is telling a pulmonologist for a patient with tuberculosis, “No need to use anti-tuberculous therapy. Just use an antipyretic and an antitussive. Just, you know, treat the fever, treat the cough. No need to treat the underlying bacteria.” And I think that’s the kind of blunt messaging we might need to explain why treating the underlying hyperuricemia is the cornerstone and foundation of managing gout, not just the clinically evident symptomatic flares. 

Dr. Larry Edwards
Yeah. Those are excellent points. 

Dr. Tuhina Neogi
I think over the last few decades, I’ve queried my primary care friends just about the problems of getting good care for gout. A lot of them will bring up the issues that, you know, they are primary care, so they’re not just looking after the occasional gout symptoms that occur, but they have, you know, the same patients might have heart disease, diabetes, various other metabolic problems, and hypertension. And for their 15-minute visits into their office, they simply don’t have time to get around it. 

I tell them that that’s really not the reason because it doesn’t take all that much effort to follow the treat-to-target approach. The same thing with nephrology. Incidentally, nephrologists follow about as many gout patients as rheumatologists do when we look at the breakdown of it, and they’ve been worried mostly about the various drugs that we use, like allopurinol, and how that might affect their kidney function. 

I think over the past decade and a half, we’ve come to recognize that these medications that we use for gout actually improve the outlook for patients that have kidney disease, et cetera. 

Dr. Larry Edwards
So yeah, I think that’s an excellent point that you made, Tahina. 

With all these various touchpoints, so that a patient with gout can encounter multiple care providers, is there a downside to that great richness of medical care that they get? Are there problems that can arise? Or is there evidence that being followed by that many physicians might actually be helpful to the patients? 

Dr. Tuhina Neogi
I think that’s a very interesting question, and I don’t know of any data to show that it’s beneficial, but I certainly have lots of anecdotal experience about some cautions that need to be taken. 

Primarily because of the lack of adequate understanding of gout and its management, a patient may be advised in different ways by different specialists. Sometimes we have patients who have a bump in their creatinine, and the kind of knee-jerk reaction is, “Oh, hold the allopurinol. It must be due to the allopurinol.” 

But we’ve had lots of data to date, including some observational data that my group has contributed to showing that allopurinol does not have a nephrotoxic effect. And so if someone does experience a creatinine bump, they should look for other causes because it’s not the allopurinol. There is likely some other reason for why their renal function has declined. 

This is particularly an issue on the inpatient consult service, where a patient is admitted, they have a decline in their renal function, and allopurinol is held. That hospitalization may be prolonged because then the patient gets a flare during that hospitalization, or they’re discharged home without re-prescribing the allopurinol. They go home and flare and may be readmitted, and this is a cycle we see over and over again. 

So one of the public service announcements that I always have our fellows be aware of, and have as one of the main communication points that they make with the teams, is, “If there’s a creatinine bump, do not hold the allopurinol. Look for another cause.” 

Similarly with cardiology, sometimes there’s concerns about colchicine with concomitant statin use and/or concern about febuxostat given the black box warning from the FDA after the CARES trial. However, now with the EMA-mandated post-marketing trial that was published in The Lancet after the ACR guideline was published, the FAST trial, we now know that with a better quality trial, there’s no overt cardiovascular concerns with febuxostat. 

So I spend a lot of time on the electronic health record, sending messages to my colleagues when they are concerned about allopurinol with renal function or about febuxostat with cardiovascular risk, to discuss with them the data and that we can safely monitor the patient together. 

Dr. Larry Edwards
I think that’s an excellent approach to continue to be a teacher of our fellow physicians and care providers right along with letting them in on what our thought process is when we see them as specialists, and we want to get everything under control. 

You’ve been a major contributor and a spokesperson for the treat-to-target approach that the American College of Rheumatology has fostered since it started putting out guidelines on the treatment of gout. Maybe we can spend just a little time talking about it in its essence, what the treat-to-target is, and in its simplest form, what therapeutic approaches we really do recommend. 

Dr. Tuhina Neogi
Sure. The general principle is to reduce the serum urate to below the level of saturation so that the urate won’t crystallize into monosodium urate crystals, which then contributes to the promulgation of inflammatory cytokines, et cetera, and manifests as the flare. 

The accumulation of MSU crystals into granulomatous tissue deposits are the tophi, and those are chronic inflammatory, low-grade inflammatory granulomatous tissues that have immune cells, osteoclasts, et cetera, contributing to bone erosions. So there’s a lot of biology that can be prevented, a lot of bad pathology that can be prevented by keeping the urate below saturation levels, and generally use less than six milligrams per deciliter. 

Though the serum levels are not a perfect reflection of total body urate burden, but they are a good rule of thumb. In prior iterations of the guideline for people with tophi, less than five milligrams per deciliter was recommended. In the most recent iteration from 2019, a separate threshold for people with tophi was not specifically recommended simply because there are no randomized trials stating that one threshold is better than another for people with tophi. 

However, there’s lots of observational data that do support that the lower you go, the faster the tophi can resolve, and that detail is in the text of the guideline, but it wasn’t made as a specific recommendation due to the lack of RCT data. In rheumatology, we’re never gonna have RCT data for every single clinically relevant question that we have. And so the ACR does try to make sure that it incorporates the whole body of scientific evidence, not just randomized controlled data. The recommendations may not be able to be strongly made when there’s lack of trial data. 

Dr. Larry Edwards
Yeah, and I think also very deeply entwined in the treat-to-target approach is the idea that this is a lifelong therapy. 

And a lot of physicians and a lot of rheumatologists don’t understand that. They’ve been on allopurinol for five or six years. They haven’t had any symptoms for two or three years, and they think it’s absolutely fine to discontinue it. But I think we must make sure to get that message to the patient so that they don’t stop it inadvertently, and to the physicians so that they aren’t complicit in that same thing. 

So I think that those are the true essences of treat-to-target, and that again is opposed to treat to avoid symptoms, where just taking the anti-inflammatory drugs or colchicine alone or in combination is the approach to get the patient out of the emergency department or to just simply make them feel good faster. 

Dr. Tuhina Neogi
Right. Part of that is to actually not have therapeutic inertia and to actually treat-to-target, meaning levels need to be checked, and doses need to be adjusted accordingly. 

I think there are many physicians who are a little nervous, perhaps about adjusting the doses too quickly, but you sometimes see someone who’s been on a dose for six months or a year without adjustment. So I think that’s another area of education is to ensure that people don’t fall into a pattern of therapeutic inertia, that they should be checking the serum urate levels and adjusting accordingly, not just checking once or twice a year in the beginning when they’re starting on urate-lowering therapy. 

Dr. Larry Edwards
Yeah, and the right dose of allopurinol cannot be judged before you actually start the therapies. The range that the FDA approves is from a hundred milligrams daily up to eight hundred milligrams daily. And to say that somebody has failed allopurinol implies that they’ve used the entire spectrum of FDA-approved dosing. 

So yeah, I think those are all important things that actually surprise some of my colleagues when I mention it to them, that they are used to capping out at three hundred milligrams in a day, and if the patient doesn’t get to the target range, then that’s just too bad. That’s where they stick for a long time. 

I think that spreading the message through our consultations will, over time, make a difference and improve things. 

Dr. Tuhina Neogi
Another area that I think is challenging to overcome in decades of practice is renal dosing of allopurinol. That again is very common in primary care, inpatient setting nephrology. And, you know, I think the paper by Handy was published in 1984, I think, if I remember correctly. So that’s decades of practice that needs to be addressed. 

And, you know, I think all that that renal dosing of allopurinol has proven is that people with renal insufficiency have inadequately managed gout with renal dosing. It has not reduced risk of allopurinol hypersensitivity syndrome by using that approach. 

Dr. Larry Edwards
Sure. And, you know, for those patients that don’t respond well to allopurinol or have a reaction to it, there are, of course, alternatives now in the form of urate-lowering therapies. 

We have febuxostat as an oral medication. We have probenecid that’s been around since, actually, the 1940s and used usually in combination with either allopurinol or febuxostat if it’s needed. And then we do have an intravenous form of therapy that’s highly effective, although it takes great buy-in by the patient because it requires a visit every two weeks to the physician’s office. But these things are out there, and to treat this disease appropriately, you have to use the entire spectrum of therapies. 

Do you have other thoughts about this, how we can be better at talking to our colleagues about how we can win them over to this approach that seems to be foreign to them, at least as I see them in my institution? 

Dr. Tuhina Neogi
Right. It is a bit puzzling because other metabolic conditions or metabolic adjacent conditions all have treat-to-target goals, such as blood pressure, cholesterol, diabetes, INR. 

You know, so why gout and urate-lowering therapy is problematic is puzzling. Now, the American College of Physicians have argued that urate is a biomarker, and that in the medical community we’ve been burned by trying to target something that hasn’t been proven to be the biologic culprit, and the example they give is estrogen for cardiovascular disease, or they provide examples of where there can be harm if something is dropped too low, like blood pressure, glucose, et cetera. 

And I think for the first, about the biologic culprit, we know urate is a biologic culprit. If you don’t have an elevated urate, you will not have gout. And as for the dangers of having urate too low, there hasn’t really been good data to show that there are major concerns. You know, one example that people give is at the turn of the century, the average serum urate was maybe around four or something, with no detriment to society at that time, and with the rising obesity epidemic, the serum urate has risen over decades. 

So I think no one is advocating for urates to be kept at almost zero for years at a time, but certainly getting urate to below six does not have any adverse effects that have ever been really demonstrated in good quality studies. So I think some of the hesitation about treatment of gout by using parallels to these other examples is really not accurate or appropriate. 

Dr. Larry Edwards
And there are diseases, specifically hereditary xanthinuria, where patients are born with a uric acid that’s barely detectable throughout their entire life, and these patients don’t suffer from the consequences of that as far as other metabolic diseases. So I think that that’s an overstressed reasoning that doesn’t hold much water at this time. 

Dr. Tuhina Neogi
To go back to the question about what else do I do or what else could we do, I often find that the best strategy is to educate our patients, because they can then go on and educate the other physicians, the other specialist physicians that they interact with. 

I often tell my patients, “Don’t let anyone mess with your allopurinol,” or whatever they happen to be on, and that before anything gets changed with those medications, the physician needs to have a conversation with me so that we can make sure we’re all on the same page and we understand the rationale for why someone may be concerned and why they want to make a change. Then we can have a conversation to see if that is appropriate, and then make a plan for that, or if more education is needed for the physician. 

Dr. Larry Edwards
Yeah. Well, that’s an excellent point, and interestingly, it was the reason that Dr. Ralph Schumacher and myself formed the Gout Education Society.

We were kind of looking around the room about 15, 20 years ago, and there was a lot of physician education that was going on because of new drugs being brought into the mix. Yet there didn’t seem to be a great turn as far as how many more patients with gout were being appropriately treated. And so we thought, “Well, if you treat the patients that are suffering with it and they believe what we’re saying, they would be their own best support system when they go into their primary care doctor’s office.” 

So that was our reasoning, and I think it’s a good approach. It’s just that there’re a lot of patients out there with gout, and it’s hard to reach everybody. But I think, as you say, that when you see them, make sure that they understand the disease, that their treatment’s gonna be lifelong, that having frequently obtained serum uric acid levels is the way to make sure that they’re on the right track.
Are there other final thoughts you have about this issue of patients seeing multiple different specialties, and how this might be confusing to them? 

Dr. Tuhina Neogi
I think one of the things that I always do is review all the medications, all the potential interactions, and also which medications may positively or negatively influence urate, so they really have an understanding holistically of what they have on their meds list. And importantly, to be adherent, not just to their allopurinol, but if they’re on a diuretic, to make sure they take their diuretic consistently as prescribed to avoid those fluctuations in urate. 

So sometimes I find that patients don’t have a clear understanding that some of their other medications may also influence their gout. Having an awareness of the potential interactions and the potential effects of other medications beyond their allopurinol can be helpful for patients to understand if a flare happens, even though they were adherent to their allopurinol, why that might have been. Maybe a new diuretic was started, and so they don’t have to beat themselves up over, you know, what did they do. 

Dr. Larry Edwards
Yeah. Those are excellent points. 

Another thing that I like to spend some time talking to my patients about is letting them know that gout is a progressive disease that should be taken seriously. 

I mentioned before that the primary care doctor might be more worried about the hypertension or the heart disease or the kidney disease, these various other comorbid events that track along with gout. But they should be thinking about gout as a disease that can be every bit as destructive as rheumatoid arthritis, can be a life-defining type of disease process. People with long-standing gout have worsening of these other comorbid diseases. It’s something that they need to be aware of, and the physicians need to be aware of. 

The other thing is that the patient should not feel guilty about having gout. 

That’s a big thing that I think we all encounter, is patients feeling a bit ashamed to mention that they have gout, when in fact it is not a disease of excessive consumption, which was the old understanding of who got gout. It was the royal families and those that just overdid on everything. But we now know that more likely this is a genetics problem, it’s a metabolic problem. It’s a diffuse inflammatory process that can worsen a lot of other conditions. And so they need to be impressed that it’s not just their occasional flare that they had to be worried about, but over time, it can be something much more major. 

Dr. Tuhina Neogi
Right. I sometimes explain it as that what we’re seeing when someone has a flare is just the tip of the iceberg, and that the flare is like a danger signal that there’s a lot of inflammation going on, and that it’s not just about the joints, but that there’s probably other systemic consequences.

Some recent work by our colleagues in Nottingham has shown that gout flares increase risk of a cardiovascular event in a relatively short window of time. And so even though gout in and of itself should be important and merits treatment, the link to elevated cardiovascular risk heightens the importance of getting gout under better control. 

Dr. Larry Edwards
Absolutely. Well, thank you for joining us today, Tahina. It’s been wonderful talking to you. 

Dr. Tuhina Neogi
Well, thank you very much. 

I just want to have one parting comment that I hope everyone adheres to. We have to stop gout apathy, because gout apathy leads to gout arthropathy. So we need to stamp out gout apathy. 

Dr. Larry Edwards
Nicely done. That’s wonderful. Let’s hand it back to you, Ian. 

Ian Ponitz
Thanks both for having this fruitful discussion today that can help those with gout, their caregivers, and medical professionals alike kick gout in the acid. If you have gout or treat gout, you can learn more through the website: gouteducation.org

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Thanks for listening in.