Gout Cavalcade (7.10.2026) Save

It's July 10, 2026. This is the RheumNow podcast. Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com. This week on the podcast, some important regulatory announcements, a cavalcade of gout information. We'll talk about why it's gout month in July on RheumNow, and information about nurse practitioners and physician assistants that we should be paying attention to.

I want to begin with what I think was the important news from last week, and that was the New England Journal printing a retraction of the ADVOCATE trial. The ADVOCATE trial was the regulatory trial that led to the approval of avacopan for ANCA-associated vasculitis. That was published in the New England Journal. And really because the authors on this paper, including David Jayne and Peter Merkel, became aware that the adjudication procedures in this trial that was done by ChemoCentryx were not kosher, and the FDA has problems with some of the data or how it was arrived at.

This led to, as you know, a series of events that started last year around October, I think, where the FDA was talking to the current owner of the compound, which is Amgen, about removing the drug from the market because of this data mismanagement, data misrepresentation. I don't think anybody believes that there's a major lie being perpetrated here or that we're being led astray and that this is all dangerous. It's just that it wasn't done the way it was supposed to have been done.

And so because of that, the FDA is very concerned. But then we start to throw in, you know, these reports of liver problems and vanishing bile duct syndrome, a very rare, very, very rare disorder. You hardly see it anywhere else, but it's been associated with this condition mainly in Japan and has a high mortality risk.

For these two reasons, there have been many interactions between the FDA and Amgen, including the FDA going on the Federal Register and saying outright that they advise the drug be withdrawn from the market. Amgen has resisted. Amgen's negotiating. Amgen's trying to have, I believe, a hearing about this. And while this is going on, the EMA in Europe, their Committee for Medicinal Products for Human Use, the CHMP, has also recommended the revocation of marketing authorization for Tavneos, or avacopan, in the EU.

This does not bode well for this compound. I'm often asked, should I be stopping my patients who are taking this drug? I wouldn't — if your patient's on the drug and not having problems with the drug, you've already passed the litmus tests, and everything that's being overemphasized here and made dramatic are pretty rare events, as best we know, especially the vanishing bile duct syndrome.

I might have reservations about starting someone on avacopan pending, because what I mean is it's a coin toss at this point whether it's going to be removed from the market or kept on the market with provisions of some sort. All I can say is stay tuned.

Also, about a week ago, the FDA was due to make a decision on Sorrento's — actually, on Sobi's new biologic license application, a BLA, for its nanoencapsulated sirolimus plus pegadricase — a uricase compound combined with nanoencapsulated sirolimus to reduce the antibodies to the PEG in pegloticase. Those anti-drug antibodies lessen the efficacy of these uricase compounds, as happens with pegloticase and why you need to use also methotrexate when you're taking that.

Anyway, this is a combined compound. This compound was originally developed as SEL-212, and then Sobi bought the product. They had some problems — they got a complete response letter from the FDA, went back to the drawing board, did another study, and now they've submitted this. Two years ago their PDUFA date, the decision date for FDA approval, was at the end of June. But the day before that was supposed to happen, the FDA issued a complete response letter to Sobi saying, "Hold on, wait a second. We need more information." And mainly the delay in the decision — this is not a denial, this is a delay in the decision — is regarding the manufacturing process of the drug, which is done by a third party out of China.

The FDA and others have said there are no concerns about the efficacy and safety of NKTR — nanoencapsulated sirolimus plus pegadricase — and we do know the clinical trials that are out there, upon which the drug would be viewed as safe and effective for FDA approval, appear to be robust. But they have to iron out this issue about how the drug is to be manufactured. The FDA is very involved. A lot of the drugs that we take here in the United States aren't made in the United States — they're made internationally — and the FDA is all over them like white on rice about how it's done. I know I've been involved in several of these decisions by the FDA on foreign-made drugs.

So those are the two big
issues that are kind of putting a monkey wrench in the new drug scene here in the United States. Let's go with something pretty basic. A study from the UK using the Clinical Practice Research Datalink, a primary care database of hundreds of thousands of patients, looked at the frequency of Raynaud's — and it's just a coding issue. The prevalence was 160,000 cases in 2023 in the UK. That's a prevalence of 984 per 100,000. That's roughly about one per thousand as the prevalence of Raynaud's. And they all show up in your clinic. That's right. All in your clinic. But that's good because you know what to do with it. The incidence rate is 46 per 100,000. It's more common as people get older. It's more common in women. It's less common in African-Americans. And in that study, less common in people who live in London. Move to London right away. Why not? I mean, it's not cold there, but it's not warm either.

Um, I like this paper coming out of Mayo Clinic Proceedings and an accompanying editorial by Jeff Sparks about a point that I'm really lecturing about these days, and that is use your best drug first. And the time has come, folks, that your best drug first is a JAK inhibitor. I don't know what you're waiting for. Oh, I know what you're waiting for. You're waiting for the price to come down. The drug — at least tofacitinib — is now generic. Look it up on GoodRx. It's like 20 bucks for a month's supply of 10 milligrams a day of tofacitinib. At least, that's what I saw when someone sent me the receipt recently. It's dirt cheap. Why would you use methotrexate over tofacitinib or a JAK inhibitor? Well, the guidelines say you have to, but the guidelines really were turning a blind eye to grade A data from clinical trials of JAK inhibitors head-to-head against methotrexate in DMARD-naive populations — and it wins all the time. ORAL START, RE-BEGIN, SELECT EARLY, FINCH 3 — JAK inhibitors beat methotrexate: easier to take, faster onset, maybe less monitoring, less nuisance side effects.

Anyway, in this issue of Mayo Clinic Proceedings there's a study out of China, 116 patients randomized — also I think it was open label — comparing tofacitinib to methotrexate, and again tofacitinib wins, by a 50% reduction of SDAI, Simplified Disease Activity Index, of 94% on tofacitinib and 75% on methotrexate. Little elevated numbers because, well, it's China and I'm not sure what that means, but I said it — and also because open label, which tends to elevate the numbers — and that's a three-month endpoint. More importantly, tofacitinib was more cost effective than methotrexate. I'm going to ask you now and I'm going to tell you later: use your best drug first, and then you tell me what your best drug is.

A review, a systematic review of 35 retrospective studies and almost 7,500 patients, looked at if you had a prior septic arthritis and then you needed a prosthetic joint, how's that going to turn out? Well, obviously you need to be far away from the septic arthritis event. While you're at it, be far away from your last steroid injection if you want to reduce the risk of subsequent PJI, prosthetic joint infections. In this study of about 4,800 knee replacements and 2,600 hip replacements, the total PJI rate was 2.6%. It was much higher with TKAs, 9.8%, than THAs, 1.1%. The risk was significantly lowered by the longer interval between the septic arthritis resolution and the day of surgery. The other thing — a big thing in the orthopedic literature — is that in these people you sometimes need to do two-stage procedures. They showed two-stage procedures had an increased risk of prosthetic joint infections, and that's going to cause a lot of orthopedists to scratch their head — hopefully not while wearing gloves in the OR.

Um, you might have remembered that in December we had a great campaign devoted to advanced practice providers, physician associates, and nurse practitioners. And one of the big things back then was that in the Trump big beautiful legislative plan, they cut the funding of graduate medical education, graduate education in general. It was unlimited before if you were going to medical school, for instance, or any professional school. Now it's capped at $200,000. But they did not designate NP and PA degrees as being professional. So hence they're capped at only $100,000 lifetime, $20,000 a year. This significantly impairs the possibility of many people receiving an NP or PA funded education from the federal government. Anyway, this was taken to court, and there was a time where people were commenting on this, but the Department of Education got a blow when a federal judge blocked this from being implemented. Now, what's going to happen after this? I'm going to guess that they're going to continue with the existing rule that people can get what they can get until this gets resolved in some way, shape, or form, but it's now null and void. This is good news for those of you who need
funding to pursue an NP or PA degree. Um, another great thing happened this week, not from the ACR. The ACR should take notice of this, but the AGA, the American Gastroenterology Association has launched a new um, AGA GI readiness and credentialing program, which I think has two different pathways for advanced practice providers to receive basically certification education um in the area of gastroenterology. That's one of the big things right now. Anybody that becomes an NP or PA in whatever discipline, they're all getting their training on the job. Most of you who are doing this, I've trained many uh NPs and PAs in my clinics, but it's through a program that I set up. Um now, there are programs at the — there's an educational program from the ACR that people can do self-learning on. Um and there's a program with RAP and we've got a series of lectures on RheumNow called advanced practice rheumatology. So there are educational opportunities but most of you who are employing NPs and PAs are not pointing your people to them, that they must get that, and certainly the AGA now has a certificate that people can wave in front of you and hopefully they get paid more when they get started there.

JAMA had a nice review about uh hepatitis B infection. It's a worldwide problem affecting 250 million um people worldwide and over a million — 1.1 million deaths in 2022. There were 14,000 HBV infections in the United States. And of course, what you need to know is what the pathologies tell you. Hepatitis B surface antigen means there's active ongoing infection if it's positive. Hepatitis B surface antibody means that there's immunity naturally acquired or if you gave the vaccine you become hepatitis B surface antibody positive and that's a comforting thing. Patients who are hepatitis B surface antigen negative but they're hepatitis B core antigen or antibody positive means that there's past infection that's been resolved. We've talked about this many times before — those people can receive TNF inhibitors with a less than 2% risk of reactivation. Probably the same would be for other biologics, but this is still a worrisome state that you want to follow carefully or with a hepatologist. If you're worried about hepatitis B, do um DNA viral testing to document the viral load for hepatitis B.

Um, Science published an article this week about a potential new target. Um and using spatial transcriptomics on synovial tissue samples they showed that the lining layer — which as you know all synovial cells, they're synoviocytes of macrophage um lineage — and these um macrophages express secreted phosphoprotein one or SPP1, that also expresses osteopontin, and the important thing is it's very rich in the lining layer and that lining layer abuts in great close proximity a ton of fibrin and fibroblasts. And we've talked in the past that we have great therapies, but we've got nothing for what's going on in the interstitium with those fibroblasts that provide all the damage to the joints these days. IL-6 inhibitors help a little bit. We have no directive therapy for the fibroblast and what's going on beneath that lining layer. It's thought that these um lining macrophages that are high in SPP1 degrade fibrin, but then in a — which is really a process of fibrin being laid down to try to repair what the body perceives as damage. But in doing so, it actually induces fibroblast proliferation that then does all the damage and all the deposit of collagen, um matrix metalloproteinases and lots of enzymes and cytokines that basically destroy the joint. Well, why not target these SPP1 macrophages or for that matter osteopontin? Again, this might be an example — we have made our greatest advances in rheumatoid arthritis by um not using bench material to develop drugs that are clinically efficacious. We have drugs that are clinically efficacious that tell us about what's going on in the pathogenesis. But this is uh — we should pursue these kinds of investigations.

Um, as you probably should know by now, this has been the first week of gout month. Um the title of the month is gout — it's more than a flare, it's more than a feeling. Um, and gout is a systemic disease. It's deadly. It's undertreated. It's hard. It's gigantically mismanaged by everyone. We've got a lot of content this week on gout, and I'm going to end with it on this podcast. Um, the global gout market is projected to go from three billion uh in 2022 to over 10 billion by 2036 in the next 14 years, basically reflecting greater knowledge, more innovation, more drug therapies. Um, you know, it says that there's um over 200,000 chronic refractory gout patients in the United States and over 400,000 worldwide in 2025. We had a journal club this week on two treat-to-target articles. One showing you treat to target, you don't have renal progression. The other one showing you treat to target and you have less cardiovascular MACE
outcomes. And interestingly, the benefit of treat was about 1% or one and a half% — well, one to 2.4% — in the two trials. And you say well that's not very much, but as Dr. Abhishek said in the journal club, in 2020 worldwide there were 55 million people with gout. It is estimated that by 2050 that number is going to grow to 96 million. You prevent death and renal death in 1 to 2%, you've done tremendous good in managing gout and saving money and lives.

An interesting study this week also looked at the outcomes from the CARES trial. You know, CARES and FAST and other trials were head-to-head studies looking at cardiovascular outcomes. They often don't talk about many of the main gout outcomes. In this one long-term follow-up, they showed that in patients treated with either febuxostat or allopurinol that the remission rates are not very good in the first year. And that's because when you give a urate lowering therapy, you're dropping urate in the blood, but then you're mobilizing urate from the tissues and there's horrible flare rates in that first year. And that's why you have to use prophylaxis with non-steroidal, low-dose prednisone, or god forbid colchicine. Don't get me started on colchicine. But in this study they showed that the remission rate was only 37% in the first year but by year six it had gone to 63% when you were on urate lowering therapy, and over the six years about 60% achieved remission at least once. It was more likely based on age, race, disease severity, comorbidities, and febuxostat was better than allopurinol in the CARES study.

A study from the Netherlands looked at the value of treat to target. You know, we are getting into this argument all the time. We believe this. This is an 8-center rheumatology center study from the Netherlands where 308 gout patients were randomized to either treat to target going at the usual target of six or less, or symptom-based management with urate lowering therapy. Everybody was starting urate lowering therapy. In the study, remission was far more common — 15% more common in T2T than symptom-based therapy: 39% versus 24%. That's significant. And guess what? Symptom-based therapy had more adverse events, 53% versus 42%.

There's a lot of this data out there and it's going to be on the website this month. You can see a target emulation trial from China — this was one of the first — both of the journal clubs that we had this week were target emulation trials in a treat-to-target exposure. And this Chinese study, they did a target emulation trial in 2,100 patients with asymptomatic hyperuricemia who had stage three and four CKD. Let me say that again: asymptomatic hyperuricemia and they have stage three or four CKD and they start on urate lowering therapy or not. At three years, renal progression — which meant end-stage kidney disease or greater than 40% decline in eGFR — was the same in both groups. So there was no benefit. But then again this is the issue: do you treat asymptomatic hyperuricemia? Is there a benefit? This is one of the studies that says there isn't.

The other renal study we did in the journal club was patients with CKD stage 3 who had gout who were starting urate lowering therapy, and there it clearly showed that there was no progression to end-stage renal disease, transplant, renal death of some sort, or dialysis.

Obesity — common issue in gout, is it not? Well, you will soon be hearing a lot about all the obesity trials and what it means to rheumatology. That's a little preview for September this year. But this SURMOUNT-1 trial was a study of tirzepatide in 2,500 people with a BMI greater than 30 or a BMI greater than 27 with obesity risk factors. And they showed that if you were on tirzepatide compared to placebo, there was a 21% weight loss by week 62. What happened to the uric acid? That was not in the original report. This sub-analysis looked at the uric acid and it turns out that whether you were taking tirzepatide 5, 10, or 15 milligrams, the uric acid levels dropped by either minus 0.7, minus 0.9, or minus 0.95. It looks like 10 or 15 milligrams per week of tirzepatide gives you these one-point drops in uric acid, and they said in the paper that weight loss explained about 73% of the uric acid reduction.

You'll see on both the email and the website this week on RheumNow a box called Gems. It'll be in the right-hand corner and it's going to be famous quotes or famous teachings or gout facts. I'm going to leave you with the five from this week. Number one: 12.1 million Americans have gout, but only 1.3% of those gout patients are seen by you, the rheumatologist. It could be as high as 2.5%, but the best number in the literature is 1.3%. We've got to do a lot here in education, do we not? Less than 40% of patients with gout are taking urate lowering therapy,
proving that they're not being managed by a rheumatologist. Wait, that 40% number, less than 40% of urate-lowering therapy treated gout patients achieve their treat-to-target of a uric acid of less than six. By the way, that's like low 30s for primary care and less than 40 for you, the rheumatologist. You're supposed to be the expert. Why are you not doing better? You kind of wimp out. You say you're doing it, but are you really?

The prevalence of gout increases with obesity. In a non-obese population, the prevalence of gout is about 1%. When you go to a BMI greater than 30, it's 7%. Sevenfold increase.

How many people have hyperuricemia? This is asymptomatic hyperuricemia, some of which are symptomatic. 15 to 20%, or up to 44 million Americans, have hyperuricemia, but only 20 to 25% of those will ever develop gout. So hyperuricemia is not the death knell for developing gout.

Black tart cherries, Montmorency cherries, or cherry extracts have been consistently shown to reduce gouty attacks. They're just as good as non-steroidals. It is the anthocyanins in the rind and the stems that are made into paste that are the most powerful. If you're telling your patients to drink cherry juice, you're wrong. It'll have some effect, but it's not as good as the paste or the pills made from black tart Montmorency cherries. Are other sweet cherries — Bing cherries, maraschino cherries — so good? Yeah, they're good, but they're less effective.

Okay, my last point. Gout affects the spine in probably around 20%. The range is 14 to 35% depending on how the study is done and whether doing MRI or CT scan, but it's proven by DECT scan or CT scan, and 14 to 35% — I think around 20%. Guess what? Most of those are misdiagnosed as discitis. So think about that patient with back pain, focal back pain, you see something ugly on the CT, it's called discitis — maybe you should be ordering a uric acid. Think about it.

That's it for this week on the podcast. Hope you enjoyed it. Go to the website, check out these citations and more. We'll talk next week.