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ACR: Treat-to-Target Endorsed for Gout

— Differs from ACP guideline for primary care: "they're wrong"

MedpageToday

ATLANTA -- Except for the earliest or mildest cases, patients with gout should be treated with urate lowering therapy (ULT) to a target of <6 mg/dL, a draft update to the American College of Rheumatology (ACR) guidelines reaffirms -- even though this treat-to-target strategy hasn't been validated in a randomized, controlled trial.

The new guidelines, to be finalized and released next year, leaders of the effort said here at the , will put the group at odds with the American College of Physicians, whose stopped short of endorsing a treat-to-target strategy.

Donald Thomas, MD, a rheumatologist based in Greenbelt, Maryland, who moderated an ACR press conference at which the draft update was discussed, skipped the diplomacy in giving his view of the squabble.

"They're wrong and we're right," he said.

Tuhina Neogi, MD, of Boston University, and co-leader of the ACR update effort, acknowledged that trial confirmation is lacking and that the 6-mg/dL cutoff is somewhat arbitrary. (Not entirely, though -- she said lab studies indicate that uric acid crystallization begins at 6.8 mg/dL under physiologic conditions.) The accumulation of observational data and clinical experience made it an easy call for the guideline panel to set this target and give it a strong recommendation.

In doing so, the group is doubling down on a treat-to-target recommendation in its , issued in 2012.

The new draft, which still must be approved by the ACR's board and then undergo journal review, specifies that ULT should be initiated in all patients with tophi, radiographic damage attributable to gout, or having two or more gout flares per year.

In contrast, ULT is not indicated for patients whose only gout-related abnormality is serum urate above 6 mg/dL -- that is, with no symptoms or radiographic indication of gout.

The guideline comes with a "conditional" recommendation for ULT in patients with more than one lifetime flare but fewer than two per year. In the ACR scheme, conditional recommendations are those with either weak supporting evidence or when the risk-benefit balance is close, such that patients may reasonably prefer another approach.

One important change from the earlier ACR guideline, Neogi said, is that it de-emphasizes lifestyle factors as a point of attack in gout. While it may still suggest weight loss and reducing alcohol, purine, and high-fructose corn syrup intake -- conditional recommendations in the draft update -- evidence shows that gout is mainly driven by non-modifiable factors such as genetics, she said.

"The key is not to blame patients," she said, noting that fear of lifestyle-shaming is a major reason patients don't seek treatment for early gout symptoms.

Other highlights of the update:

  • Allopurinol is the only recommended first-line agent for ULT, irrespective of renal function
  • Febuxostat (Uloric) is a reasonable choice as second-line ULT, even in patients with cardiovascular disease
  • Pegloticase (Krystexxa) should be reserved for patients who don't meet serum urate targets with other therapies
  • ULT doses should start low and then titrate upward
  • Colchicine, NSAIDs, or glucocorticoids (by any customary route) are appropriate as first-line treatment for gout flares

Endorsement of febuxostat in patients with heart disease (a conditional recommendation) may surprise some clinicians, given findings of the so-called CARES trial that showed increased rates of cardiovascular and all-cause mortality. Neogi said the trial had many flaws and questions about interpretation. Moreover, she said, a patient focus group convened to inform the guideline update said they would accept some risk in order to be free of gout. Neogi noted that some patients may have exhausted other treatment options, such that the risk-benefit balance should ultimately be the individual patient's decision.

Disclosures

Guideline panel co-principal investigators Neogi and John FitzGerald, MD, declared they had no relevant financial interests. Certain other members of the core leadership team reported relationships with industry.