Conventional oral urate-lowering therapies frequently to fail to achieve target serum uric acid (sUA) levels in patients with chronic kidney disease and uncontrolled refractory gout. This can lead to increased urate burden and complications, including worsening kidney disease, cardiovascular events, and metabolic syndrome. Tune in to find out how to incorporate targeted therapies when managing uncontrolled refractory gout and improve your patients’ quality of life.
What’s New About Gout? Rheumatology Perspective
What’s New About Gout? Rheumatology Perspective
Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.
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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?
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.
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?
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.
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?
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.
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.
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.
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.
And thanks, everyone, for tuning in.
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In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all its educational programs.
Richard Johnson, MD
Professor of Medicine
University of Colorado
Anschutz Medical Campus
Research: National Institute of Health
Ownership Interest: Colorado Research Partners, XORTX Therapeutics
Receives Royalties: Elsevier, BenBella Books
Consulting Fees: Dinora, Horizon Pharma
Abdul A. Abdellatif, MD, FASN
Division of Nephrology
Baylor College of Medicine and CLS Health
No relevant relationships reported
John K. Botson, MD, RPh
Director of Rheumatology
Orthopedic Physicians Alaska
Research: Horizon Therapeutics
Patent Holder: Horizon Therapeutics
Consulting Fee: AbbVie, Amgen, Eli Lilly, Horizon Therapeutics, Novartis
Brittany Weber, MD, PhD
Director, Cardio-Rheumatology Clinic
Associate Physician, Prevention Cardiology & Cardiovascular Imaging
Brigham and Women’s Hospital
Research: AHA, NIH
Consulting Fees:, Agepha, Horizon Therapeutics, Kiniksa, Novo Nordisk
- Cindy Davidson has nothing to disclose.
- Hany Ibrahim, MD, has nothing to disclose.
- Samantha Keehn has nothing to disclose.
- John Maeglin has nothing to disclose.
- Brian McDonough has nothing to disclose.
- Tim Person has nothing to disclose.
After participating in this educational activity, participants should be better able to:
- Discuss the pathophysiology and prevalence of high uric acid levels and uncontrolled gout in patients with renal disease and the contribution of chronic gout to chronic kidney disease (CKD) progression, associated comorbidities, and increased mortality
- Apply knowledge of available diagnostic tools to identify patients with elevated serum uric acid (sUA) levels early in the progression of CKD to initiate proper urate-lowering therapy (ULT) and reduce urate burden
- Summarize the limitations of standard ULT options in patients with CKD
- Incorporate emerging urate-lowering therapies, including pegloticase-methotrexate combined therapy and clinical trial evidence, into clinical practice in the treatment of appropriate patients with uncontrolled gout
- Discuss gout as an independent risk factor for CVD and its association with CVD morbidity and mortality, necessitating early screening and treatment to attain target sUA levels
This activity is designed to meet the educational needs of nephrologists, rheumatologists, cardiologists, primary care physicians, and others who encounter, diagnose, and treat gout.
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Global Learning Collaborative (GLC) designates this enduring activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Global Learning Collaborative (GLC) designates this activity for 1.0 nursing contact hour. Nurses should claim only the credit commensurate with the extent of their participation in the activity.
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This activity is supported by an independent educational grant from Horizon Therapeutics, USA, Inc.
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