ACP Updates Gout Guidelines: Abandoning Treat-To-Target?

New evidence-based guidelines for managing gout released by the American College of Physicians (ACP) recommend that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout and use low-dose rather than high-dose colchicine when prescribing this drug to treat acute gout.

The guidelines, published in the Annals of Internal Medicine, also recommend that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy (ULT), including concomitant prophylaxis, in patients with recurrent gout attacks.¹ The guidelines recommend against initiating ULT in most patients after a first gout attack and in patients with infrequent attacks.

“High-quality evidence showed that corticosteroids, NSAIDs, and colchicines are effective treatments to reduce pain in patients with acute gout,” Amir Qaseem, MD, PhD, MHA, of ACP, and coauthors wrote on behalf of the ACP’s Clinical Guidelines Committee. “Gout symptoms are mostly caused by inflammatory reaction to the deposition of urate crystals, which results from an increase in serum urate level above it saturation point in the blood.”

Corticosteroids should be considered as first-line therapy in patients without contraindications because these drugs generally are a safe and a low-cost treatment option, the guidelines state.

With regard to the use of low-dose colchicine for acute gout, the guidelines state that moderate-quality evidence suggests that lower doses of the medication (1.2 mg followed by 0.6 mg 1 hour later) are as effective as higher dosing (1.2 mg followed by 0.6 mg/hour for 6 hours). Higher dosing should not be used—especially in patients with chronic kidney disease (CKD)—due to toxicity.

Evidence was insufficient for gout-specific dietary advice or therapies to improve symptomatic outcomes, according to the guidelines.

With respect to monitoring serum uric acid levels in gout sufferers, the guideline committee said evidence “was insufficient to conclude whether the benefits of escalating urate-lowering therapy to reach a serum urate target (‘treat-to-target’) outweigh the harms associated with repeated monitoring and medication escalation.”

Although studies have demonstrated an association between lower urate levels and fewer gout flares, the studies did not establish that ULT rather than other patient characteristics caused the decrease in flares, Dr Qaseem and coauthors wrote.

“Further, even if urate-lowering therapy does reduce gout flares, these studies do not help us understand the tradeoff between the magnitude of benefit and the harms and costs incurred by treatment and monitoring,” they stated. “Thus, we remain uncertain about the value of a treat-to-target strategy compared with a strategy of basing treatment intensity on minimizing of symptoms.”

In this regard, the ACP guidelines differ from recommendations made by the American College of Rheumatology (ACR), which recommend that the goal of ULT is to achieve a serum uric acid target, at a minimum, of less than 6 mg/dL in all gout case scenarios.² 

The ACR also recommends that “the target serum urate should be lowered sufficiently to durably improve signs and symptoms of gout, including palpable and visible tophi detected by physical examination, and that this may involve therapeutic serum urate-lowering to below 5 mg/dL.”

In an accompanying editorial, Tuhina Neogi, MD, PhD, of Boston University School of Medicine and Ted R. Mikuls, MD, MSPH, of the University of Nebraska Medical Center in Omaha, pointed out potential shortcomings of the treat-to-avoid-symptoms approach suggested in the ACP guidelines.³

“With this strategy, providers might consider suppressive anti-inflammatory therapy or treatment of each flare as a sufficient strategy without addressing underlying hyperuricemia,” Drs Neogi and Mikuls wrote. “When patients never receive ULT or receive inappropriately low doses, ongoing urate deposition occurs, leading to progression of tophaceous deposits, further joint damage, and functional limitations.”

Commenting on the ACP guidelines, gout specialist Anthony J. Bleyer, MD, professor of nephrology at Wake Forest School of Medicine in Winston-Salem, North Carolina, told Renal & Urology News: “The current ACP guidelines fail to address gout prevention in patients with chronic kidney disease. This is unfortunate, as CKD is the most common cause of gout, and the prevalence of gout increases markedly with worsening stages of CKD.  Specifically, prescribing allopurinol in the setting of CKD is a major concern.”

The 2012 ACR guidelines, Dr Bleyer said, better address this area, stating allopurinol at doses even greater than 300 mg/day can be used “in renal impairment” provided there is adequate patient education of possible adverse risks and that there is regular monitoring for drug sensitivity. Unfortunately, he said, this recommendation is based on suboptimal evidence, and it is important that physicians read this recommendation in its entirety when deciding on allopurinol dosing for their patients. 

Febuxostat is much more expensive, but it has been well studied and shown to be well tolerated with eGFR values as low as 15 ml/min/1.73m², according to Dr Bleyer.

“It is clear that both sets of guidelines prefer allopurinol—due to cost—even though febuxostat is better studied and does not have as severe adverse effects as allopurinol,” Dr Bleyer said. “In the end, issues of safety versus cost must be discussed with the patient when prescribing allopurinol versus febuxostat in CKD.”

References

1. Qaseem A et al. Management of acute and recurrent gout: A clinical practice guideline from the American College of Physicians. Ann Intern Med 2016 Nov 1. doi: 10.7326/M16-0570 [Epub ahead of print]
2. Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res (Hoboken). 2012;64(10):1431-46. 
3.  Neogi T, Mikuls TR. To treat or not to treat (to target) in gout. Ann Intern Med 2016 Nov 1. [Epub ahead of print] 

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This article originally appeared on Renal and Urology News