ACR 2021: 7 New Things to Know About Gout

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At the American College of Rheumatology/Association of Rheumatology Health Professionals Annual Meeting this year — ACR Convergence 2021 — more than 16,500 attendees and 600 speakers from more than 100 countries gathered virtually to share the latest research and address the most pressing issues for people living with rheumatic disease.

The CreakyJoints team soaked it all in — listening, watching, and learning so we could bring you the most relevant information to ensure you know what you need to better manage your condition and get better care.

We combed through hundreds of studies, attended sessions from top gout experts, and asked our team of patient and physician advisors to share the gout updates they deemed most important for patients.

The result: Our curated, patient-friendly guide to gout research and trends from ACR 2021. For more research breakthroughs from ACR 2021, check out our main guide: 100+ Arthritis & Rheumatic Disease Updates You Need to Know.

1. When dosed appropriately, allopurinol is not inferior to febuxostat in the treatment of gout

Allopurinol (Aloprim, Lopurim, Zyloprim, and generics) is often recommended over febuxostat (Uloric) for gout patients when starting uric acid-lowering therapy — but is one better than the other in the management of gout?

A team of researchers from University of Nebraska Medical Center and Boston University School of Medicine, among others, set out to find the answer in a 72-week trial (now referred to as the “stop gout” study) done in the veteran’s hospital and funded by the Veterans Association (VA). It included 950 patients who were randomly given allopurinol or febuxostat to lower serum urate levels.

The results: Allopurinol was not inferior to febuxostat and produced similar flare rates — for both patients with and without significant chronic kidney disease (CKD). Overall, 80 percent of patients achieved target uric acid levels (below 6.0 mg/dL) and nearly 90 percent achieved levels below 6.8 mg/dL, with no difference according to uric-lowering treatment. There was also no difference in patients with CKD.

“This trial demonstrates that titrating urate-lowering therapies to serum urate targets can reduce important clinical outcomes of gout flares, and that allopurinol, when titrated to doses greater than 300 mg, works about as well as febuxostat, which is a more expensive medication,” Boston University rheumatologist Jean Liew, MD, told CreakyJoints.

“That’s an important finding since allopurinol is 19 times cheaper than febuxostat, at least at the VA, and because of the black box warning [due an increased risk of cardiovascular and all-cause mortality compared with allopurinol],” the study’s lead author James O’Dell, MD, said in a RheumNow video.

Talk to your health care provider about which urat- lowering therapy is best for you.

2. Pegloticase plus immunomodulatory drugs is safe and effective for severe gout

While pegloticase (Krystexxa) has been found effective for treatment-resistant gout, it is also highly immunogenic (or capable of producing an immune response even at low doses), which can prevent it from working in some patients. Because of this issue, researchers have been studying whether giving the medication along with immunomodulatory drugs could make pegloticase more effective.

Researchers enrolled 20 patients with uncontrolled gout who received concomitant immunomodulatory drugs, including methotrexate and azathioprine. In addition to substantial decreases in uric acid levels, patients who completed 24 weeks of treatment had reductions in pain and disability.

“Gout is a chronic, systemic, and progressive disease that needs to be treated early and aggressively,” Brian LaMoreaux, MD, MS, Medical Director of Medical Affairs at Horizon Therapeutics, which manufactures pegloticase, told Healio Rheumatology. “This new analysis of real-world experience of pegloticase from the ACR RISE database adds to the body of data supporting the effective and safe use of concomitant immunomodulation for this subset of patients and suggests using concomitant immunomodulation co-therapy improves pegloticase persistence. These findings are consistent with previous clinical trials and in-practice analyses.”

3. Treat-to-target may reduce cardiovascular disease risk in gout patients on urate-lowering drugs

Hyperuricemia, or high uric acid, is a risk factor for increased cardiovascular comorbidity and mortality — and many experts believe that treating high uric acid levels with a urate-lowering drug may reverse or reduce the risk in patients with gout. However, the cardiovascular safety of uric acid-lowering medicine has also been questioned, so it’s important to understand the trade-offs of using higher doses of medicine to reduce heart disease risk.

Researchers from Brigham and Women’s Hospital set out to determine how different treat-to-target strategies, including more tight control and routine regular monitoring, could improve gout and reduce the risk of cardiovascular disease.

Using Medicare claims data, they identified more than 4,400 gout patients who took either the uric acid-lowering medications allopurinol or febuxostat. Researchers emulated a hypothetical target trial that compared the risk of major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular mortality) of gout patients receiving several different treat-to-target strategies. TTT strategies included: continuation of urate lowering therapy, regular serum acid (SUM) monitoring, and timely modification of ULT if uric acid levels exceeded target (above 6.0 mg/d).

They found a decreased rate of cardiovascular events in patients who followed any treat-to-target strategy compared to those who started urate-lowering therapy but didn’t follow a treat-to-target strategy. However, when researchers looked at different ways of treating to target, they didn’t observe differences in risk reduction among them.

The findings: “One thing we can say for sure is that it doesn’t look like the tight control or treat-to-target strategy is worsening the risk of cardiovascular disease,” study author Seoyoung Kim, MD, of Brigham and Women’s Hospital, said in a RheumNow video.

That said, Dr. Kim noted that they don’t want to overinterpret the data, as good treatment behavior patterns (taking meds as prescribed, following up with your doctor, getting regular blood tests) could also contribute to decreased risk of cardiovascular disease.

4. Omega-3 fatty acids do not lower uric acid levels but research is ongoing when it comes to gout flares

Omega-3 fatty acids are believed to be beneficial for people with gout (as well as for other inflammatory conditions) because they inhibit substances that cause inflammation in the body. But do omega-3 supplements have a direct impact on preventing gout flares or reducing levels of uric acid? (When high levels of uric acid, which is normally a waste product, accumulate in the blood, it can crystallize in the joints, leading to painful gout attacks.)

In a small pilot study, researchers set out to examine the effects of omega-3 supplementation with fish oil on serum urate (SU) and weight and body mass index (BMI) in people with gout. The goal was to determine whether it could help prevent flares in people starting urate-lowering therapy. They found no statistically significant difference in SU, weight, or BMI, however there was a correlation between supplementation and the total number of flares between week 12 and 24 of the trial.

“They did not see a beneficial effect on flares or serum urate, though biologically I don’t think we would have expected an effect on serum urate, so I think some questions remain: Are we using the right dose of fatty acids to truly get the inflammatory effect,”  rheumatologist and epidemiologist Tuhina Neogi, MD, said in a RheumNow video. “I’m hoping that the book is not closed yet on omega-3 fatty acids.”

5. You should be working with your doctor to treat gout as a chronic disease, not just for symptom management

The benefits of urate-lowering therapies for symptoms like flares and tophi are well-studied, but more research is needed on how adequate gout treatment impacts long-term health outcomes.

In a large VA study of gout patients, researchers looked at the effects of urate-lowering therapies on all-cause mortality (death for any reason). They found that the use of urate-lowering therapy was associated with reduced mortality — and if patients reached a target under 6 mg/dL, there was an even greater association with reduced mortality.

“Sub-optimally treated gout was associated with a higher risk of death compared to well-treated gout,” Boston University rheumatologist Jean Liew, MD, told CreakyJoints. Researchers defined “well-treated” gout by prescription fills of urate-lowering therapies and measures of uric acid using VHA pharmacy and laboratory data.

“The study emphasizes the importance of treating gout as a chronic disease with urate-lowering therapies, such as allopurinol or febuxostat, rather than treating for symptoms/gout flares only,” says Dr. Liew.

6. Breakthrough COVID infections are common among vaccinated patients with gout

Unfortunately, vaccinated patients with certain rheumatic diseases have been found to have increased odds of breakthrough COVID infections – and this includes patients with gout.

An analysis from a U.S. nationally sampled electronic medical record data repository, compared 47,303 rheumatic disease patients to 536,954 controls. Researchers discovered that breakthrough infections varied by rheumatic disease, with rheumatoid arthritis, spondyloarthritis, and gout topping the list.

While uric acid-lowering medications don’t suppress the immune system, gout patients may be more vulnerable to COVID-19 breakthrough infection because of other factors, like age or certain comorbidities, such as diabetes. Some patients may also be taking corticosteroids like prednisone to manage gout flares, which have been associated with increased risk for COVID-19.

The takeaway: If you have gout, continue to practice COVID safety measures and make sure to get a COVID-19 vaccine booster. Read more here about COVID-19 vaccine updates in rheumatic disease patients.

7. Uric acid can accumulate in the spine, causing back pain

While gout typically affects the big toe, it can cause pain, swelling, and inflammation in other joints, too. But what about your spine?

Researchers set out to determine whether gout could affect the lumbrosacral spine in patients with and without tophaceous gout by doing CT scans to check for the presence of uric acid. They enrolled 50 gout patients (some who had tophi and some did not) and 25 controls who did not have gout.

“Roughly 50 percent of the gout patients seemed to have evidence of urate deposition in the spine,” study coauthor and NYU rheumatologist Michael Pillinger, MD, said in a RheumNow video. “One patient had severe back pain and bad gout and the back pain went away when we treated the gout.”

Experts hope these findings remind physicians (and patients) that “urate is an equal opportunity depositor — and it’s probably in more places than we think it is,” said Dr. Pillinger.

The takeaway: If you have gout, don’t blow off back pain. Talk to your health care provider to determine if uric acid could be the culprit.

You Can Participate in Gout Research Too

If you are diagnosed with gout or another musculoskeletal condition, we encourage you to participate in future studies by joining CreakyJoints’ patient research registry, ArthritisPower. ArthritisPower is the first-ever patient-led, patient-centered research registry for joint, bone, and inflammatory skin conditions. Learn more and sign up here.