An Overview of Gout Treatment

In this video, Robert Terkeltaub, MD, gives an overview of the two current standards of care in the treatment of individuals with gout, including the role of a multidisciplinary team and a treat-to-target approach for lowering serum urate to avoid progression from acute to chronic disease. 

Additional Resources:

• Elsaid K, Merriman TR, Rossitto LA, et al. Amplification of inflammation by lubricin deficiency implicated in incident, erosive gout independent of hyperuricemia. Arthritis Rheumatol. Published online December 1, 2022. Accessed March 14, 2023. https://doi.org/10.1002/art.42413
• New look at an ancient disease: study finds novel treatment targets for gout. News release. University of California San Diego; December 13, 2022. Accessed March 14, 2023. https://today.ucsd.edu/story/new-look-at-an-ancient-disease-study-finds-novel-treatment-targets-for-gout 

This video has been shared with permission from Consultant 360. Watch the original here.

Robert Terkeltaub, MD, is a professor of medicine emeritus in the Division of Rheumatology, Allergy and Immunology at the University of California, San Diego. 

TRANSCRIPTION:

Hi, I'm Bob Terkeltaub and I'm a Professor of Medicine Emeritus at UC San Diego and I'm a rheumatologist.  

There are really two standards of care. There's the usual care. What I mean, is that most gout is treated in primary care; well over 90%. Yes, some gout is treated in the emergency department and some gout is treated by nephrologists as part of their global mission of care of patients with CKD in particular. But basically, there's a usual standard of care that's endorsed by the American College of Physicians for primary care physicians. And that needs updating. And then there's the rheumatology standard. 

So, the “usual standard of care” is to treat to avoid symptoms and minimize the gout flares. And for that, there is no consensus about using urate-lowering therapy, about any targets for urate-lowering therapy. And then the schism is wide because the rheumatology model is that gout is an intermittently symptomatic disease that's progressive to chronic disease with joint damage, and marked by symptomatic periods of gout flare activity. Typically acute gouty arthritis flares. But it's really a chronic disease. 

And really the way to have better outcomes - established now in large randomized clinical trials, multiple trials - is to treat to serum urate target. That gets the patient to a serum urate well below the upper limit of normal and prevents new monosodium urate crystal formation. It also promotes the relatively slow process of the dissolution of existing deposits in the joint tissues and the soft tissues of monosodium urate crystals. The outcomes that are improved include not simply gout flare activity, which takes about 12 to 24 months to occur, a slow process achieved by our oral therapies. But the outcomes also include impeding the progression of the disease. And eventually, to do it right, you treat to a serum urate target with a bare minimum being less than six milligrams per deciliter. A lower target is used if people have a palpable tophaceous disease that's indicative of chronicity of the arthritis as well as a high urate crystal and body urate burden, There, the target can be less than five milligrams per deciliter as a bare minimum. 

And so, we have a big problem, because we have two standards of care. There's new information that should make people think seriously about gout flares being more than a temporarily incapacitating event, a nuisance, and so forth. The evidence is really stunning. It was a manuscript from Cipolletta and colleagues from Nottingham in the UK that was published in late 2022 in JAMA. That is a very high-impact journal. It’s really the flagship journal for primary care. The work indicates that a recent gout flare, meaning a gout flare within the last 60 days, is associated with a doubling of the combined risk for acute myocardial infarction and stroke. And then a fivefold risk of lethal myocardial infarction or stroke. So, gout flares are not benign, and we have to do, everything in our power to try to limit these flares. 

Unfortunately, the limitation of dietary triggers alone is not enough. The measures that people take to limit gout flare dietary triggers are good overall health measures to control dietary excesses once you have gotten gout over many years. That may be  20, 30, 40 years, but often less. In the typical middle-aged patient, it may have taken 20, 30, 40 years to get gout because of genetics and comorbidity factors. Conversely, it takes a long time to resolve those crystal deposits and to reverse and really improve the course of the disease. And the best diets on the planet that are palatable typically only lower the serum urate by about 15% max. Of course, you want to avoid dietary flare triggers. Excesses in alcohol and steaks, et cetera, can be very enjoyable but they do trigger flares. But just limiting dietary excesses will not typically get the average gout patient to the serum urate target of less than 6 milligrams per deciliter. Especially if you look at clinical trials where the average serum urate is 9.5, if you drop that by 15%, you come up well short of the urate target. Even if you have a serum urate of 8 mg/dL, you're not going to get to the serum urate target. You certainly can limit more of the acute gout flares by limiting these flare triggers. But treatment to target urate lowering is the way to go. 

There are other benefits besides the ones mentioned when it comes to joint disease. The increased all-cause and cardiovascular mortality in gout patients also is reduced by urate-lowering therapy. The initiators of urate-lowering therapy who maintain urate-lowering therapy do better overall. Many gout patients have quite a lot of comorbidity; hypertension, about 70% plus; obesity, up to 50%; similar for metabolic syndrome, and patients very commonly have type 3 diabetes; and also chronic kidney disease; with coronary artery disease also common. These are the most common comorbidities. So, people are often on a lot of medications and their issues such as chronic kidney disease or drug interactions limit the options that we have for treating gout flares and for lowering the serum urate,  and the drugs and dosing that we can use to do so. 

We want to clean up gout flares. And we want to do better in managing gout. We now know that 5% of USA adults have the disease according to the data that are emerging from NHANES. Previously published data was 4% of USA adults. Regardless, we are talking about more than 10 million adults in the United States with gout. No more than half are treated with urate-lowering drugs. Of the people that are treated with urate-lowering drugs, a minority are treated to target because there are two standards of care. I think that we must do a lot better. And we are hampered by fake news and disinformation, medical disinformation, on the usual social media sources. There's a lot of uncertainty that patients have about the safety, value, and risk-benefit ratio of the treatments that we offer. 

So, many patients with gout are not very adherent. Particularly, and without stereotyping, the medical literature indicates that the younger males who have the disease are less adherent. They have fewer doctor visits and are less established in primary care. And then, in focus groups, some of the younger population with gout report that they feel that they can overpower the disease and control the disease, and they don't like taking meds. I don't like taking meds either. I doubt you do. People don't want to be on a lifetime of urate-lowering therapy, which is usually what's required. 

So, yes, we can do a lot better. We have a lot of gout patients, there are two standards of care. Now the gout management guidelines are redone every 5 years in primary care. And we're hoping that when the writers of the guidelines take into account all the new literature that's come out, especially new clinical trials, they'll take into account that there's abundant evidence that treats to target urate-lowering therapy really works. We want to clean up gout so it’s no longer one of the multiple active medical problems that patients commonly have.