The Need to Revisit Treatment Approaches for Gout

While gout has historically been associated with overeating, mounting evidence indicates that gout is a chronic metabolic disease caused by a mix of genetic, environmental, and lifestyle factors. Furthermore, physicians have recently pointed out that the condition’s complex, chronic nature is often overlooked, which has led to ineffective care for many patients.

Rheumatologist Nicola Dalbeth, MD, a gout expert at the University of Auckland in New Zealand who helped draft the 2012 recommendations, emphasized the need to revisit best practices for the treatment of gout with an unbiased approach. “We need to be looking at the alternative models of care for gout management,” Dalbeth said. “[We need to see] gout as a chronic disease and take those chronic care models that are used so often in diabetes, hypertension, anticoagulation and apply them to gout as well.”¹

Gout affects about 4% of adults in the United States. It causes inflammation and severe pain when high levels of uric acid from crystals form in patients’ joints. Common risk factors like obesity, hypertension, kidney disease, and hyperlipidemia are increasing gout’s prevalence. Growing use of diuretics and other medications that increase uric acid levels are compounding the issue. The proportion of older adults who are affected by this disease is expected to rise, which is alarming, because patients often go untreated or undertreated, resulting in joint damage and worsened comorbid conditions.

Diet misconceptions and differing guidelines surrounding the make treatment decisions for the condition more difficult. While much of the focus remains on patients’ diets, guidelines state that dietary changes are likely to cause a mere 10% to 18% decrease in uric acid levels, which are percentages that are not enough to dissolve uric acid levels. In fact, “Most patients with gout don't even know that it's a form of arthritis,” according to N. Lawrence Edwards, MD, a rheumatologist and chair of the Gout & Uric Acid Education Society (GUES).¹

In addition, while a low purine diet has been recommended, Dalbeth believes, “It’s just unpalatable and not sustainable for most people.” Emphasis on diet also makes patients more reluctant to take medications when they are given reason to believe diet alone can help.¹

“[Patients] don't appreciate that this is really a metabolic disease that's genetically determined and needs to be treated seriously, just like blood pressure and heart disease and kidney disease,” Edwards added. However, Hyon Choi, MD, a rheumatologist and director of clinical epidemiology at Massachusetts General Hospital, pointed out that, “Without the strong, clear-cut data, it's difficult to convince each other anything. At some point, this needs to be resolved with additional data or some sort of consensus and unified guideline.”¹

Aside from diet misconceptions, discrepancies between different guidelines and pharmacologic treatments add to the confusion of gout patients’ care. The 2012 guideline—the American College of Rheumatology’s (ACR) first on treating gout—declared a treat-to-target approach, which focused on lowering serum uric acid levels below 6 mg/dL in patients with 2 or more flares a year or other indications through the use of urate-lowering medications long-term with frequent monitoring.

In contrast, the 2016 guideline from the American College of Physicians (ACP) suggested a treat-to-symptoms approach with an emphasis on the use of anti-inflammatory medications to control flares and decrease uric acid levels. This approach uses uric acid-lowering therapy for patients with frequent flares, but evidence of longer-term benefits is uncertain.

As of late, rheumatologists have also stressed the importance of addressing long-term consequences in patients with poorly-managed gout, such as joint damage, chronic arthritis, and declining kidney function. Due to its irreversible nature, physicians suggest that treating gout in a timely manner is crucial.

Leslie Harrold, MD, MPH, associate professor of medicine and orthopedics at the University of Massachusetts Medical School, emphasized the importance of a dual treatment. “It's like treating 2 different diseases, or trying to explain to patients the 2 different treatment approaches you need to take. One is to affect the acute manifestations, and then the other is to prevent the chronic problems that occur with gout.”¹

As of today, allopurinol and febuxostat are the recommended first-line uric acid—lowering therapies in both guidelines. While allopurinol is known to cause allergic reactions in some people, a low- and slow-dose escalation is recommended by the ACR. However, allergy caution aside, allopurinol is known to be effective as long as the uric acid levels are monitored while on the medication since doses may need to be adjusted in accordance with fluctuating uric acid levels. In addition, the US Food and Drug Administration (FDA) has also linked febuxostat to an elevated risk of heart-related death, so clinicians should discuss treatment options with their patients.

More treatment options include the FDA-approved a new uric acid-lowering drug for patients who don’t experience their targeted success with allopurinol. The new drug uses both allopurinol and lesinurad in an attempt to simultaneously inhibit uric acid overproduction and poor excretion. Other drugs that address the inflammatory pathways involved in gout are currently in development. They may be used to treat the acute phase of the disease (the release of interleukin 1b, which causes an inflammatory cascade).

The ACR and ACP plan to meet in April to reconcile differing approaches to better improve care for patients with gout. The ACR’s gout guideline is scheduled for an update in 2020, while more research is on the horizon. However, studies in the US and UK have shown that patient education helps patients reach their treatment goals, so shaking the “disease of kings” label appears necessary for effective gout treatment.

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References:

1. “Chronic Disease Approaches Needed to Curb Gout’s Growing Burden.” Journal of American Medicine. 3 Apr. 2018

Image by Gabriel Caponetti