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.
Can You Manage Patients With Uncontrolled Gout More Effectively?
Can You Manage Patients With Uncontrolled Gout More Effectively?
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This is CME on ReachMD. I’m Dr. Abdul Abdellatif. Here with me today, Dr. John Botson, a rheumatologist from Alaska.
John, how do you manage our patients with uncontrolled gout more effectively nowadays?
The important thing to realize is that gout is not a joint problem in itself. It’s a systemic inflammatory process very similar to diabetes or high cholesterol and coronary artery disease. It’s something that we not only need to treat the acute episodes and pain, but also, we need to treat the patient so that we can prevent these other comorbidities and cardiovascular risks, especially, from happening.
The first is the patient hurts, so you’ve got to treat their acute illness. And this one I say with a little grain of salt talking to a nephrologist, but we use things like NSAIDs and colchicine and prednisone unless there’s a reason they can’t. But we’re using these intermittently, hopefully only in the beginning until you can get the gout more in control and prevent them from getting to that uncontrolled stage. Many patients still blame themselves for flares, many providers still blame patients for flares when, really, we need to recognize that this is also a genetic disease. It’s something that you’re born with. Your diet plays a small role in this.
We really have a couple sort of standard medications that we’ve used for decades: uric acid-lowering agents, or xanthine oxidase inhibitors, as we call them, allopurinol, febuxostat. And these are agents that block an enzyme that prevents the uric acid levels from going up. So they’re bocking the xanthine oxidase. They work well in most patients. The side effect profile is generally pretty minimal. We do watch for some allergic reactions with allopurinol, and there was a recent concern about cardiovascular disease with the febuxostat that’s still under debate.
Uricosurics we do use occasionally. They’re not as widely used. They’re definitely not used in your population as a nephrologist. They have some small uric acid-lowering benefits. The patients that are really suffering are in those difficult-to-treat cases of refractory gout, or what we call uncontrolled gout. By definition, they failed uric acid-lowering agents, those xanthine oxidase inhibitors; they’ve either not tolerated or failed uricosurics or you can’t use them. We’ve got 1 drug FDA-approved right now and that’s pegloticase. It will lower the uric acid to undetectable, and it’s safe in patients with all stages of kidney disease. It’s not a corticosteroid, so even diabetics can use it. This uricase breaks down the serum uric acid into something called allantoin, which is really water soluble and freely excreted.
There was a recent trial that actually improved upon pegloticase in using a combination with methotrexate that stopped the antidrug antibodies from being developed and essentially improved its efficacy and its safety. So in rough numbers, almost doubling the efficacy and about 8 times the improvement in safety for this medication in combination.
So that’s really kind of set the bar now of where our treatment is. And so essentially, our goal in all these patients, whether we’re using a xanthine oxidase inhibitor or a uricase, is to get the serum uric acid below that solubility level. We often shoot for a level of 6. In patients that have severe gout we’ll shoot or a level of 5.
But ultimately, when we’re initiating treatment, lower is better for these patients to get them under control. And then once we’re sufficiently under control, then we use some of these other agents to move forward and to keep the patients at that level.
We actually took 20 patients of our kidney transplant patients who had had their transplant for at least a year in a steady state of immunosuppressive therapy, and we just gave them pegloticase based on protocol. And we were able to actually get 89% of these patients to respond to the treatment, and we were able to get them basically gout symptom free within 6 months of therapy, and we did not have even a significant infusion reaction or any cardiovascular events out of the greater than 200 infusions that we gave to our patients. So the drug does help our patients at all stages of kidney disease, normal dialysis, peritoneal dialysis, hemodialysis, even our transplant patients.
Well, this has been a brief and a great discussion. Unfortunately, our time is up. Thank you all for listening.
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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.
In support of improving patient care, Global Learning Collaborative (GLC) is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
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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