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? Nephrology Perspective
What’s New About Gout? Nephrology Perspective
Welcome to CME on ReachMD. This episode is part of our MinuteCE curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
This is CME on ReachMD, and I am Dr. Abdul Abdellatif. Here with me today is Dr. Richard Johnson.
Richard, what is the emerging evidence that can change our treatment plans for managing our patients with uncontrolled gout in the renal clinic?
A big study in heart disease was called ALL-HEART, in which thousands of patients were treated with allopurinol versus usual care followed through several years to see if there was any effect on reducing heart attack. And these were people who had had prior heart disease, and yet there was no benefit. They were actually not targeting the right population. They weren’t even targeting people with high uric acid. They were targeting any person with heart disease, and about over 50% of the patients dropped out.
Similarly, there were 2 studies looking at lowering uric acid in patients with chronic kidney disease. The PERL trial, which was in type 1 diabetics, and the CKD-FIX trial, which was patients with stage 3 and 4 CKD. They didn’t include patients with gout.
So I don’t view any of those trials as really saying that lowering uric acid is not beneficial in patients with gout. We know it’s beneficial in patients with gout. We know it reduces the gout attack. We know it reduces inflammation. And there’s data that it can reduce cardiovascular mortality and kidney disease progression.
Abdul, what do you think are some of the more important new studies?
Thank you, Rick. We actually looked at 152 patients in the MIRROR trial that was recently published. And actually, not only did it have benefit to the patients, it led to the FDA changing the label on the medication that when you treat patients with pegloticase, it’s better if you use pegloticase with methotrexate. Why? Because when we actually did this clinical trial, we randomized patients to either be on pegloticase by itself or pegloticase with methotrexate to control the immune system to prevent the drug from being eliminated from the body very quickly. And we showed that we actually improve the response rate of these patients from 39% complete response rate to 71% complete response rate at 6 months. So we know if we use the appropriate therapy to target our patients with uncontrolled gout, we can do a better job with the new advancement in treatment of patients with uncontrolled gout.
We also studied pegloticase in patients with transplant. For patients with lower GFRs, we know that if you look at the PROTECT trial that I presented, because not only we wanted to show that it benefits patients across the board – if they have kidney disease, they don’t have kidney disease, they’re patients with transplant – and we showed in our transplant patients from about 20 patients that we studied that had had their transplant for at least 1 year, and we know gout is more prevalent in the transplant population; almost 13% of our transplant patients have gout. We actually showed those patients with uncontrolled gout, if we gave them pegloticase, we had about 89% of those patients’ response to therapy with zero infusion reaction, no cardiovascular events, and no anaphylaxis at week 21. As for the transplant patients, they’re already on immunosuppression agents, so you only have to give them the pegloticase.
Methotrexate can accumulate and, you know, be toxic in patients with really bad kidney function. So at what level do you use methotrexate? Is there a cutoff of the GFR, and what do you do if the GFR is below that?
In the MIRROR clinical trial we studied, one-third of the patients had moderate chronic kidney disease. We did not study patients with severe chronic kidney disease of GFRs less than 30, but we were cut off at 40 GFR. For those patients who were studied, we did not see any nephrotoxicity; we did not really see any hematological side effects of the drug or abnormal liver function tests or muscular complaints of those patients. So we know at the level of 15 mg that was used weekly for those patients, the patients tolerated the treatment very well and, independent of their kidney function, they all did very good with the therapy compared to pegloticase by itself.
It was a good discussion and, thanks, that’s our time. Thank you for joining us.
You have been listening to CME on ReachMD. This activity is provided by Prova Education and is part of our MinuteCE curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/Prova. Thank you for listening.
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.
Prova Education designs and executes continuing education founded on evidence-based medicine, clinical need, gap analysis, learner feedback, and more. Our mission is to serve as an inventive and relevant resource for clinical content and educational interventions across a broad spectrum of specialties.
Prova Education's methodology demonstrates a commitment to continuing medical education and the innovative assessment of its effects. Our goal is clear—to develop and deliver the very best education in the most impactful manner and to verify its results with progressive outcomes research.
This activity is supported by an independent educational grant from Horizon Therapeutics, USA, Inc.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Prova Education. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to access a site outside of Prova Education you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.
Reproduction of this material is not permitted without written permission from the copyright owner.
Our site requires a computer, tablet, or mobile device and a connection to the Internet. For best results, a high-speed Internet connection is recommended (DSL/Cable/Fibre). We also recommend using the latest version of your favorite browser to ensure compliance with W3C standards, such as Chrome, Safari, Firefox, or Microsoft Edge.