Stop treating gout and start curing it, physician urges

LAS VEGAS – Brian F. Mandell, MD, PhD, of Cleveland Clinic, has a message about one of the most devastating conditions that rheumatologists see: Gout isn’t just a treatable disease. It’s a curable one.

Dr. Brian F. Mandell

Still, research shows time and time again that physicians manage gout “horrendously,” he told colleagues at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “The problem really lies with us,” he said. “We need to do a better job.”

At issue, he believes, is a failure to consider the basic workings of gout when making treatment decisions and advising patients. Lowering serum uric acid (SUA) via medication works, he said, but physicians too frequently don’t go far enough with this approach.

Gout appears to be on the rise in the United States, reflecting increases in related conditions such as obesity and diabetes. A study published this year found that the rate of new-onset gout more than doubled in Olmsted County, Minn., from 1989-1992 to 2009-2010, reaching an adjusted rate of 137/100,000 (J Rheumatol. 2018 Apr;45[4]:574-9).

According to Dr. Mandell, various mysteries regarding gout still need to be cleared up. For one, does resolution of gout also resolve conditions related to hyperuricemia, such as onset of hypertension, progressive chronic kidney disease, and nonalcoholic fatty liver along with higher all-cause mortality?

“We don’t know from interventional studies whether these are as reversible as the gouty arthritis,” he said.

It’s also unknown why so many hyperuricemic patients don’t get flares, with one study estimating that about 50% don’t get them over 15 years (Arthritis Rheumatol. 2017;69[Suppl 10]: Abstract 2843).

One fascinating theory, Dr. Mandell said, suggests “the microbiome is playing a huge [role] in the body’s response to deposits of crystals.”

Fortunately, he said, other mysteries about gout are being solved.

It’s now clear that lowering SUA below 6 mg/dL with medication will reduce flares, Dr. Mandell said. He pointed to a 2017 study of 314 patients with early gout that found 63% of patients who took febuxostat (Uloric) lowered their SUA below 6 mg/dL, compared with just 6% of the placebo group. The overall percentage of patients who had at least one gout flare over 2 years was 29% in the febuxostat group vs. 41% in the placebo group (Arthritis Rheumatol. 2017;69[12]:2386‐95).

It’s also clear that maintenance of lower SUA levels is crucial to prevent recurrence, Dr. Mandell said.

So why is management of hyperuricemia so poor? He ticked off various possible explanations: Maybe it’s the medications. Or perhaps patient compliance is low.

But the drugs are fine, he said, although he cautioned that too-rapid lowering of SUA levels can provoke attacks. He pointed to a 2014 study that suggests allopurinol can help nearly all patients get their SUA below 6 mg/dL, and in the study, the drug was “generally well tolerated” (Semin Arthritis Rheum. 2014 Aug;44[1]:25-30).

As for compliance, Dr. Mandell said, it can be boosted by patient education. The problem, he said, is that physicians are failing patients by not up-titrating allopurinol despite evidence that this approach works.

He added that hyperuricemia can be managed even in patients on diuretic therapy (Arthritis Res Ther. 2018;20:53).

What about patients who are intolerant to allopurinol or don’t fully respond to it on the SUA front? Dr. Mandell said he likes to try febuxostat, although he noted that it’s tremendously more expensive than allopurinol in the United States with a price that could be 10 times higher.

The nonscored design of febuxostat pills makes dose adjustment difficult in patients, he said, and there are concerns about heart-related and all-cause deaths.

Lesinurad (Zurampic) may be helpful for patients with hyperuricemia that doesn’t response to high doses of xanthine oxidase inhibitors (XOI) or if they’re intolerant to lower inadequate doses, he said. Avoid the drug in patients with chronic kidney disease, he cautioned, and be aware that it’s not approved as a monotherapy. Instead, it’s approved by the Food and Drug Administration for use with an XOI.

As for other gout issues, Dr. Mandell said pegloticase (Krystexxa) via infusion can help patients who don’t respond to an XOI but infusion reactions can occur (mainly in nonresponders), and it’s extremely expensive (about $20,000 per month).

He added that anti–IL-1 therapy is effective in hospitalized patients with gout and doesn’t exacerbate other conditions.

Dr. Mandell disclosed various links to drug makers that produce treatments for gout. He has served as clinical investigator for Horizon, has been a consultant to AstraZeneca, Ironwood, and Horizon, and has received honoraria (unrestricted grants) for continuing medical education activities from Takeda and Horizon. He also reported soliciting advertisements for a journal and educational grants for CME activities.

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