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Dr. Johnson:
This is CME on ReachMD. I’m Dr. Richard Johnson, and here with me today is Dr. John Botson.
John, how is the treatment of uncontrolled gout changing, and what opportunities exist that could benefit our patients?
Dr. Botson:
We’re now just realizing that uncontrolled gout is not just a joint problem but actually a systemic disease characterized by uncontrolled inflammation. The one thing that I think is changing the most is we have to be more aggressive in this disease treatment, and agents are really lacking for uncontrolled gout.
Really, right now we have pegloticase, which has been around since 2010. There was a significant improvement after having the MIRROR RCT trial showing that immunomodulation with methotrexate does help both the efficacy and the safety of the medication. But outside of that, there’s no other FDA-approved uncontrolled gout treatment. And then there’s a lot of other research going on right now looking at, well, ways to also help control gout flares, different mechanisms, potentially IL-1 inhibition, potentially inhibition of the inflammasome.
Dr. Johnson:
Uncontrolled gout is really much more common in patients with kidney disease because they can have such a high urate burden. They get these terrible tophi and draining lesions from their hands and so forth. You actually may have to lower uric acid to levels lower than we would normally target.
What do you think about how low we should go in the treatment of uncontrolled gout?
Dr. Botson:
The lower you go, the bigger the differential that you create with the serum uric acid and the faster these things will resolve if there’s been deposition. So solubility is 6.8 for uric acid in the blood, and so we shoot for 6 in those patients that are having recurring gout flares, but if you’re already behind the eight ball per se and someone has years of deposition, you may need to go lower, below 5, below 4. Some of the medications like the uricases can take serum uric acid levels to undetectable, which ultimately leads to a lot faster tophi resolution and really a best chance of getting patients controlled when they’ve had decades of uncontrolled gout and all the problems that have gone with it.
Dr. Johnson:
Now this is really an important point, that just treating to 6 may not be enough in someone with severe crystalline tophaceous gout. Recent studies show that urate crystals can be found in as many as 85% of patients with gout. It can be found in their blood vessels, particularly in plaque, like in the coronaries, the aorta, the carotids.
I think when we talk about uncontrolled gout, it’s not just a rheumatologic problem. It’s a general medical problem that’s very significant; it carries with it morbidity and mortality. I’m sure you agree with this, that this should be viewed like a medical emergency. How do you view it?
Dr. Botson:
It has the same risk, in my mind, as diabetes or coronary artery disease. These patients have just as much risk for other medical comorbidities and death because of the chronic inflammation, and that’s how we need to look at this. It’s another risk factor.
Dr. Johnson:
Yeah. Gout is a systemic disease, and uncontrolled gout is when you have the inflammation at the highest level with the highest risks for the patient. So it’s really something, you know, more than just the joints of the wrists and the ankle and the toes. It can even affect the spine and other sites of the body as well.
Dr. Botson:
Yeah, I think as our imaging techniques get better and we start to understand this disease better, we’re going to be able to make much bigger advances in preventing people from getting to the tophaceous uncontrolled-type gout situation and treating them earlier.
Dr. Johnson:
And, John, you’ve been the leader in this field with some of your work on pegloticase and its ability to really help resolve and disintegrate the crystals and to help people with uncontrolled gout. So thank you for what you’ve brought to the literature here.
Dr. Botson:
My pleasure.
Dr. Johnson:
And thanks, everyone, for tuning in.
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