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Gout Update from CreakyJoints

COVID-19 may have changed the format of this year’s annual medical meeting of the American College of Rheumatology — it was held completely virtually — but the pandemic did not disrupt the sharing of important research that directly impacts people living with gout.

The CreakyJoints team 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.

We curated this guide to gout research and trends from ACR that you should be aware of.

For more research breakthroughs from ACR 2020, check out our main guide: ACR 2020: 100+ Arthritis and Rheumatic Disease Updates Patients Must Know About.

 1. Diet plays only a small role in elevated uric acid levels

Gout experts have long known this, but it’s important to see data that backs up the fact that dietary changes can only go so far in reducing uric acid levels. (Uric acid is a normal waste product. When high levels accumulate in the blood, it can crystallize in the joints, leading to painful gout attacks.)

An international team of gout researchers sought to study the relative contributions of different gout risk factors on lowering uric aid levels, including certain genetic variations, diet, weight (BMI), alcohol intake, the use of diuretic medications, sex, and age.

What they found: “Changes in uric acid related were very small compared to the changes you can get with a uric acid-lowering medication such as allopurinol,” says CreakyJoints advisor Theodore Fields, MD, a gout expert and rheumatologist at Hospital for Special Surgery in New York City. “The changes with allopurinol were 10 times greater than with diet.”

This demonstrates the importance of taking medication to lower high uric acid levels and not assuming or hoping that diet changes alone can treat high uric acid.

This is also good news for gout patients who find it difficult to follow a very restrictive low-purine diet.

“I feel that we can allow our patients to have a normal diet, within reason, and [optimize] the dosing of their urate-lowering therapy to achieve that goal,” said Ireland-based rheumatologist Richard Conway on RheumNow. “We have highly effective treatments for reducing [uric acid] available … an overly restrictive diet can take much of the joy from life and the benefits may not justify the sacrifice.”

2. A diet high in fast food increases uric acid levels (but because of weight gain)

In other research on the role of diet in gout, researchers from Massachusetts General Hospital reviewed data from a group of 3,122 people who were being studied over a long-term period mainly to assess cardiovascular risk factors. This group filled out surveys about their diets and had regular lab tests and doctor’s visits. The researchers classified their diets based on how often they ate fast food and looked at uric acid levels at the beginning of the study and then 15 years later. People who ate the most fast food had a greater increase in uric acid levels over the study period than people who ate the least, “but the increase was relatively small,” notes Dr. Fields. “The authors suggested that the uric acid increase may be more related to weight gain than specific foods.”

This research, along with the study above, “supports the need for medication in most gout patients,” says Dr. Fields.

 3. The uric acid-lowering drug febuxostat might be safer than previously thought 

When people with gout need to take medication to preventively lower uric acid levels (high uric acid in the blood is what triggers gout flares), they are commonly prescribed a drug called allopurinol. Another medication that works similarly to allopurinol called febuxostat (Uloric), received a black box warning from the U.S. Food and Drug Administration (FDA) last year because a study found that there was a higher cardiac and overall death rate for people on febuxostat than on allopurinol.

However, there were a few problems with that study (called the CARES trial) that called the results into question. “Rheumatologists were skeptical of the CARES conclusions overall, and several other studies had not found a cardiovascular risk of febuxostat,” says Dr. Fields.

At ACR this year, the results from a different study (called the FAST trial) did not show any difference in the death rates between people taking febuxostat compared to allopurinol.

In this study, there were more than 6,128 gout patients already taking allopurinol; then half were randomized to start febuxostat instead. They were then followed for five years. Both groups had comparable withdrawal rates (people who stopped taking the medication) of around 5 percent, roughly the same number of gout flares, and no differences in adverse events.

“This research should give some peace of mind to patients on febuxostat,” says Dr. Fields. “We will likely still tend to use allopurinol before febuxostat, but for people on febuxostat we really don’t have much reason to be concerned about its cardiovascular safety relative to allopurinol.”

4. ‘Immunomodulation’ helps make pegloticase, a medication for chronic gout, much more effective

Uric acid-lowering medications such as allopurinol and febuxostat are staples of gout treatment, but for some patients these medications don’t work well enough to reduce gout flares, or they’re not tolerated.

At this point, people may be good candidates for an intravenous medication called pegloticase (Krystexxa), which can dramatically lower uric acid levels over a short time. However, pegloticase is only effective about 40 percent of the time because many people form antibodies to it. This causes the medication to stop working for them or causes them to have reactions to it, says Dr. Fields.

At ACR this year, “a number of studies addressed a new strategy to prevent people from forming antibodies to pegloticase by using a medication with the pegloticase that suppresses antibody formation,” says Dr. Fields. “The goal is to have a medication that decreases antibody formation but still has a low risk of side effects.”

Three medications studied for this purpose are commonly used to treat other rheumatic conditions such as rheumatoid arthritis and lupus. They are methotrexate, azathioprine (Imuran), and mycophenolate mofetil (Cellcept).

“These studies were small, but all suggested that the medications added to pegloticase all had a low risk of side effects during the treatment period, generally three to six months.  All of them increased the effectiveness of the pegloticase,” says Dr. Fields.

For example, in one study, 68 percent of people who were given mycophenolate along with pegloticase were able to maintain low uric acid levels (less than 6 mg/dL) after 24 weeks compared with 30 percent of people who got a placebo drug with pegloticase.

“This is hopeful data that using this strategy of combined medications can allow more patients with severe gout to respond to pegloticase,” Dr. Fields says.

On RheumNow, rheumatologist Alexa Meara, MD, described the findings as a “shift in gout management and uric acid lowering therapy.” She also noted “there might be further benefits in using such concomitant immunosuppressants since these drugs are also anti-inflammatory.  Maybe gout should be also approached to treat the inflammation not just to decrease the serum uric acid.”

5. Gout is an independent — and underestimated — risk factor for cardiovascular disease

Cardiovascular disease is common in people with gout, but it’s unclear what’s behind the risk. Is it that people with gout have health issues that are also linked to cardiovascular disease, such as obesity, high blood pressure, and diabetes? Or is gout a separate risk factor for cardiovascular disease?

New Zealand researchers shared data that concluded that gout is an independent risk factor for cardiovascular disease. They studied a group of 441,723 people who had a cardiovascular risk assessment during a primary care doctor visit. Of these, 23,229 people met the definition of having gout. When researchers looked at the number of cardiovascular events (such as heart attacks) within five years of the assessment and compared rates among people with gout and people without, they found that women with gout had a 24 percent increased risk of cardiovascular events and men with gout had a 21 percent increased risk.

What’s more, they found that traditional heart disease risk assessments underestimated cardiovascular events in gout patients, especially in women.

Research like this is important for gout patients and providers to be aware of in order to manage other heart disease risk factors (such as cholesterol or high blood pressure) and ensure patients get appropriate heart disease screening and treatment.

6. What’s the link between gout and type 2 diabetes? New research emphasizes the role of insulin resistance

Studies that observe groups of people with gout have found links between type 2 diabetes and gout, but it’s not clear whether gout may cause diabetes, diabetes may cause gout, or there’s some other confounding factors at play. Researchers from Massachusetts General Hospital did an analysis of genetic variations — some that were strongly linked to high uric acid levels and others that were linked with type 2 diabetes and related metabolic issues, such as insulin resistance.

They learned that genetically raised insulin levels — a precursor to type 2 diabetes — seems to play a role in causing high uric acid levels, not the other way around.

This could mean that treatment plans that focus on lowering insulin resistance could, in fact, also lower uric acid levels — and gout. However, the opposite may not be true. Treatments that target lowering uric acid might not lower the risk of type 2 diabetes.

7. Gout patients who visit the emergency department for flares miss an opportunity for better gout treatment

A gout flare can be one of the most suddenly painful experiences — many patients say even brushing their toes against a bedsheet is intolerable. It’s no wonder, then, that many people visit the emergency department to get help for a gout flare. But data from Rutgers researchers in New Jersey found that nearly 30 percent of gout patients are discharged from the emergency department without an anti-inflammatory medication (which is the first-line choice for treating a flare). As well, initiation of uric acid-lowering therapy, such as allopurinol and febuxostat, was rare.

“Treatment of gout in the [emergency department] is sub-optimal and often does not follow established guidelines,” the study authors concluded. If you visit the emergency department for a gout flare, that’s a sign you should be following up with the primary care doctor who treats your gout (such as an internist or rheumatologist) to look at your treatment and decide whether a change is needed.

8. It’s important for people with gout to continue uric acid-lowering medications when hospitalized

Researchers at Abington Hospital in Pennsylvania looked at the medical charts of gout patients who were hospitalized for reasons other than gout and were taking the uric acid-lowering medication allopurinol outside of the hospital. People whose allopurinol was stopped during their hospital stay (the reasons for this are unclear) were 14 times more likely to have a gout flare than people who were able to keep taking the medication while hospitalized.

“Understanding the role of continuation of [uric acid-lowering therapy] in the inpatient setting is of paramount importance in decreasing the risk of gout flare in hospitalized patients,” the study authors concluded.

9. Gout is often negatively portrayed in movies and TV shows

Researchers from New Zealand and Germany analyzed depictions of gout in film and TV since 1990 using databases such as Internet Movie Database (IMDb) and others. They found that gout was often portrayed as “as a humorous and embarrassing condition, caused by dietary indulgence,” according to the study authors. Overindulgence of food and alcohol was the most commonly depicted cause, while depictions of biological causes were infrequent. When gout management was discussed, there was an emphasis on changes in diet and pain relief — and only one mention of uric acid-lowering therapy.

These kind of media messages “can influence patients to blame themselves for their gout,” says Dr. Fields. “We know that gout is largely a genetic disease and that it has excellent treatments, but if people think it’s all because of what they eat and drink they may not seek out care or may not stay on their medications.”

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.

Baraf HS, et al. The Impact of Azathioprine on the Frequency of Persistent Responsiveness to Pegloticase in Patients with Chronic Refractory Gout [abstract]. Arthritis & Rheumatology. November 2020. 

Botson J, et al. A Multicenter, Efficacy and Safety Study of Methotrexate to Increase Response Rates in Patients with Uncontrolled GOut Receiving Pegloticase (MIRROR): 12-Month Results of an Open-Label Study [abstract]. Arthritis & Rheumatology. November 2020.

Brunetti L, et al. Readmission Risk and Quality of Care in Patients Presenting to the Emergency Department with Gout Flares [abstract]. Arthritis & Rheumatology. November 2020.

Cai K, et al. The Association Between Gout and Cardiovascular Disease Outcomes: Assessment and Recalibration of Individual-level Primary Prevention Risk Prediction Equations in Approximately 450,000 New Zealanders [abstract]. Arthritis & Rheumatology. November 2020.

Conway R. The Folly of Dietary Restriction in Contemporary Gout? RheumNow. November 8, 2020.

El Ramahi MK. FAST, FREED, CARES, & CONFIRMS: A Run-Down on the Black-Box Blues of Febuxostat. RheumNow. November 10, 2020.

Interview with Theodore Fields, MD, gout expert and rheumatologist at Hospital for Special Surgery in New York City

Khanna P, et al. Reducing Immunogenicity of Pegloticase (RECIPE) with Concomitant Use of Mycophenolate Mofetil in Patients with Refractory Gout—a Phase II Double Blind Randomized Controlled Trial [abstract].Arthritis & Rheumatology. November 2020.

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MacDonald T, et al. Long Term Cardiovascular Safety of Febuxostat and Allopurinol in Patients with Chronic Gout: The Febuxostat versus Allopurinol Streamlined Trial (on Behalf of the FAST Investigators) [abstract]. Arthritis & Rheumatology. November 2020.

McCormick N, et al. Assessing Causal Associations of Urate Levels with Type 2 Diabetes and Related Glycemic Traits Using Bidirectional Mendelian Randomization abstract]. Arthritis & Rheumatology. November 2020.

Meara A. Mitigating Immunogenicity When Using Uricase Therapies as ULT. RheumNow. November 7, 2020.

Minalyan A, et al. The Discontinuation of Allopurinol in the Inpatient Setting and the Risk of Gout Flare: A Community-Hospital Experience [abstract]. Arthritis & Rheumatology. November 2020.

Murdoch R, et al. “An Apple Pie a Day Does Not Keep the Doctor Away.”Fictional Depictions of Gout in Contemporary Film and Television [abstract]. Arthritis & Rheumatology. November 2020.

Song Y, et al. Pharmacokinetics of Pegloticase and Methotrexate Polyglutamate(s) in Patients with Uncontrolled Gout Receiving Pegloticase and Co-treatment of Methotrexate [abstract]. Arthritis & Rheumatology. November 2020.

Topless R, et al. The Comparative Effect of Exposure to Various Risk Factors on the Risk of Hyperuricaemia: Diet Has a Weak Causal Effect [abstract]. Arthritis & Rheumatology. November 2020.

Yokose C, et al. Fast Food Habits and Serum Urate Change in Young Adults: 15-Year Prospective Cohort Analysis [abstract]. Arthritis & Rheumatology. November 2020.

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