This rapid growth has spurred on a worldwide "gout epidemic," James O'Dell, MD, Robert L. Grissom professor of internal medicine and vice chair and chief of rheumatology at the University of Nebraska Medical Center, in Omaha, who, told the attendees at the American College of Rheumatology Covergence 2021 annual meeting.

"When I say epidemic, of course, that's kind of lost in the overuse of the word now because of the pandemic that we're living in," O'Dell told Healio in an interview following the meeting. "However, when we look at the average serum uric acid level in the United States today, it's in the mid-five range, and when we look at the numbers from 100 years ago, it was in the mid-three range.

"And so, with the Western diet, increasing obesity, with the aging population, with the lack of estrogen replacement therapy in women and several other factors, the serum uric acid levels have gone up dramatically in the average American and average citizen around the world, because it's not just the United States having this problem," he added.

James O'Dell

On top of its rising prevalence, O'Dell further characterized gout as one of the "most mismanaged" chronic conditions in medicine, specifically excoriating the American College of Physicians, and its guidelines that call for a more conservative urate-lowering strategy, compared with those endorsed by the ACR, as an example of that mismanagement.

"There is a big controversy in the gout treatment world between the American College of Rheumatology and EULAR, which are the experts in rheumatology in Europe and the United States, versus the American College of Physicians," O'Dell told attendees during the ACR Convergence press conference in November. "The American College of Physicians does not recognize how important it is to treat gout to a target of a low uric acid level."

It was, at the time, the latest salvo in what has become an ongoing battle over the use of treat-to-target between the ACR and ACP guidelines for a disease that, globally speaking, is only getting worse.

Global Domination

In late 2020, the Global Burden of Disease Study, published in Arthritis & Rheumatology, found that the global prevalence of gout doubled from 20.2 million cases in 1990 to 41.2 million cases in 2017 .  The same study found that global incidence had also doubled during that time, from 3.6 million to 7.4 million.

Meanwhile, in the United States, gout has emerged as the most common form of inflammatory arthritis, antagonizing approximately 4% of Americans, compared with less than 1% for rheumatoid arthritis, according to data published in Arthritis & Rheumatology in 2019.

According to Tuhina Neogi, MD, PhD, professor of medicine and of epidemiology, Alan S. Cohen professor of rheumatology, and chief of rheumatology at the Boston University School of Medicine and Boston Medical Center, gout has been on the rise particularly in developed countries.

Tuhina Neogi

"The Global Burden of Disease Study provides some insights about what may be contributing to the doubling of the prevalence of gout in just under 30 years," Neogi told Healio. "There has been a rise in the global population and increase in life expectancy over that time, but that alone is not sufficient to explain this dramatic increase in gout prevalence."

Similarly, an increase in recognition among physicians, leading to more diagnoses, also fails explain this large increase.

Instead, Neogi -- along with O'Dell -- identified the rise in obesity and "Westernized diets" as potential key factors. The prevalence of obesity doubled in the United States over the same period examined by the Global Burden of Disease Study. Meanwhile, according to Neogi, the global age-standardized prevalence of obesity increased by at least twofold in 13 of the 20 most populous countries.

"Similar to gout, the rise in obesity tracks with the sociodemographic index, suggesting the need for a close examination of the social determinants of health that are likely contributing to gout burden in such a compressed timeframe," she said. "Thus, there may be additional societal level factors to consider, such as physical activity and more Westernized diets, including more high-fructose corn syrup, as examples."

Gout: The reason you went to medical school

However, none of this should be a problem, in theory, as gout management is relatively straightforward. In fact, according to O'Dell, gout is the exactly the kind of disease people go to medical school to treat.

"One of my colleagues said it best when he was talking to medical students: Gout is the disease you went to medical school to treat," he said. "It gives people the worst pain that they've ever had. You can see that patient and, with a simple test done in your office, make a definitive diagnosis. And you can get them on therapy that's going to prevent them from ever having problems again the rest of their life. If they take that medicine, they're going to be pain-free from their gout for the rest of their life. What can be better than that?

"You're taking a patient from the worst pain they've ever had to a life where they don't have to have that anymore," he added. "And the alternative is having gout attacks all the time and developing these horrible deposits underneath the skin and may contribute to an increased incidence of digit amputations." 

However, according to one 2019 study published in Arthritis & Rheumatology, only33% of patients with gout in the United States are receiving urate-lowering therapy.

For O'Dell, part of the reason for this mismanagement is a general "lack of respect" for the disease, and the debilitating pain it can trigger, in popular culture as well as among some physicians. He added that noncompliant patients, too, shoulder some of the blame.

"The medical profession, I think, has not given gout very much respect," O'Dell said. "It's clear that they don't because gout is horribly mismanaged. There's been a number of studies that have been done stating that gout is among the most mismanaged chronic conditions by physicians, and of course, that's contributed to by patients' noncompliance and not wanting to have to take a pill every day for the rest of their life, which you need to do when you have gout."

For Neogi, the lack of appropriate education about the disease and its management is a major issue.

"The bulk of gout management occurs in primary care," she said. "Outdated terminology regarding 'acute' gout and 'chronic' gout also creates a false dichotomy in gout management, leading providers to incorrectly assume that one does not need to treat the underlying hyperuricemia until the disease is 'chronic'.""

According to O'Dell, the fact that most patients with gout are treated in primary care -- where most physicians are inclined to allow the ACP guidelines -- is another issue contributing to mismanagement.

"What happens to the average patient who gets started on therapy for their gout? This is from data across the country, different centers and whatnot that have looked at this," he said. "Primary care takes patients with gout, and when they put them on therapy to lower their uric acid, they put them on 300 mg of allopurinol, and they never check the uric acid level again. And that is what happens with majority of patients with gout.

"There's no reason why primary care doctors can't take great care of gout," he added. "It's just that many of them, for reasons that aren't clear, don't."

Dueling guidelines

The most recently updated ACR guidelines for gout treatment were published in 2020. They include strong recommendations for urate-lowering therapy (ULT) in all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares; allopurinol as the preferred first-line ULT, including for those with moderate-to-severe chronic kidney

Disease; using a low starting dose of allopurinol -- 100 mg per day or less, and lower in patients with chronic kidney disease -- or febuxostat -- less than 40 mg per day -- and a treat-to-target management strategy with a serum urate target of less than 6 mg/dL.

The ACP guidelines, last updated in 2016, on the other hand strongly recommend that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs or low-dose colchicine to treat patients with "acute gout." It also recommends against starting long-term ULT in most patients after a first gout attack or in those with infrequent attacks. Another strong recommendation counsels that clinicians discuss benefits, harms, costs and individual preferences with patients before starting ULT, including concomitant prophylaxis, in patients with recurrent gout attacks.

"The ACP guidelines were published online in 2016, and have not been updated since," Neogi said. "That guideline effort did not consider data from the pegloticase trial, published in 2011, that demonstrated lower risk of gout flares and higher likelihood of tophus resolution l with pegloticase lowering serum urate to below 6 compared with placebo."

Since then, a nurse-led trial in the United Kingdom also demonstrated improved flare and tophus outcomes at 2 years with a treat-to-target strategy, versus usual care by primary care physicians, she added.

"A study in early gout also demonstrated lower flare after 2 years," Neogi said. "Thus there are a number of studies that support the link between lowering serum urate with improvements in clinical outcomes."

According to O'Dell, the ACP have a "very strict interpretation" for what they include in their guidelines based on the available evident.

"And unfortunately, when it gets right down to it, in terms of evidence that supports most recommendations, it's imperfect," he said.

"I think that the American College of Physicians does a great job with so many things, but one place that they have gotten things wrong is when they make recommendation to their providers about treatment of gout," O'Dell added.

However, O'Dell conceded that rheumatologists don't always have -- "and most frequently we don't have" -- the studies required to address specific questions regarding ULT, including double-blind, randomized, controlled trials supporting lowering uric acid levels in patients with gout to certain levels.

"It's hard to find that," he said. "That's the apparent reason that the ACP give, that they don't recommend treating to a target of low uric acid level because there is no hard evidence that shows if you do that, patients do better in terms of the number of gout flares that they have. And on the one hand, that is true."

On the other hand, it is a known fact, physiologically, that 6.8 mg/dL is the upper threshold after which uric acid comes out of solution and deposits in patients' tissues, according to O'Dell.

"We know that. It's a biochemical fact," he said. "So, it follows that anything above that is not healthy. And so, we need to get everybody below that if we want them to be healthy from the standpoint of uric acid levels. The ACP guidelines would basically say, 'Well, the patient is not having any symptoms and as long as you can keep them symptom-free with whatever, then you don't really need to worry about what the uric acid level is.' And that just flies in the face of common sense. It flies in the face of what we know about hard and fast physiologic properties of uric acid in the human body."

A spokesperson for the ACP declined to comment or provide an interview for this story.

However, slides from a presentation given at the 2019 ACP Massachusetts Chapter meeting, by then ACP President Robert McLean, MD, FACP, of the Yale School of Medicine, offer a defense of the organization's guidelines.

"ACP cannot endorse the treat-to-target approach because there is not strong enough evidence to tell us it is the right thing to do," the presentation slides noted, in part. "Of course, treating the pain of acute gout (treat-to-avoid-symptoms) is appropriate, in ways that have proven effective."

According to McLean in the presentation, the ACP guidelines do not include any statements advising physicians to treat patients only to avoid symptoms, and do not specifically recommend against ULT. In addition, they do not tell physicians to avoid treatment decisions based on serum uric acid levels.

"But those were conclusions attributed to ACP guidelines," the slides continued. "Stating, 'There is not evidence to clearly endorse,' is not the same as saying, 'Do not do that.""

However, according to Neogi, it is "critically important" for all physicians managing gout to understand that without monosodium urate crystal deposition, there is no gout.

"Thus, lowering of serum urate to below saturation thresholds is the foundational cornerstone of gout management," she said. "Appropriate management of hyperuricemia in gout can prevent joint damage and tophi. Unfortunately, we as rheumatologists frequently are witness to the consequences of inadequate management, which contributes to avoidable burden of disease.?

References:

• Safiri S, et al. Arthritis Rheumatol. 2020;doi:10.1002/art.41404.
• Chen-Xu M, et al. Arthritis Rheumatol. 2018;doi:10.1002/art.40807.
• McLean R. "Rheumatology for the Internist: Why Are Gout Guidelines So Controversial?" Presented at: ACP Massachusetts Chapter meeting; November 2019.

OUR COMMENTS:

One thing this article does is point out just how misunderstood Gout is in the medical world, especially considering the level of pain is virtually unimaginable and greatly overlooked.  The conflicting ideas on treatment are not surprising and neither is the lack of care to explore natural ways to address high uric acid levels in the blood before the points of attack.  We have a great deal of respect for our medical professionals, but the lack of training from a nutritional and preventative standpoint remains a point of contention for those of us that have seen and assisted in natural means of Gout/Disease control.

FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)

Gout Sufferers: Is Allopurinol Safe and Effective?

Is Colchicine (Colcrys) a Safe and Effective Gout Treatment?

Treatment for Gout