Super-Low Uric Acid May Not Be Best for Erosive Gout

Lowering the serum urate target to less than 0.20 mmol/L (<3.6 mg/dL) for patients with erosive gout does not achieve better gout outcomes and leads to more medication use and subsequent side effects, according to findings from a 2-year, double-blind, randomized, controlled trial.

Nicola Dalbeth, MD, of the bone and joint research group, department of medicine, faculty of medical and health sciences at University of Auckland (New Zealand), and coauthors noted that intensive serum urate lowering is difficult to achieve with oral urate-lowering therapy (ULT) and their findings suggest lower is not always better.

Their data, published in Arthritis & Rheumatology, suggest the less-intensive standard target of less than 0.30 mmol/L (<5.4 mg/dL), currently recommended by rheumatology guidelines, is sufficient.

The more intensive target leads to a high medication burden and does not improve bone erosion score in erosive gout, the authors found.

Rheumatologist Angelo Gaffo, MD, associate professor of medicine at the University of Alabama at Birmingham, who was not part of the study, said erosion scores are the best way to test outcomes and this study provides support for current gout treatment approaches.

“It is reassuring that the approach of treating to target is a good approach,” Gaffo said. “The very, very low targets were not better than the [standard target].”

The trial included 104 participants with erosive gout on oral ULT who were randomized either to a serum urate target of less than 0.20 mmol/L or less than 0.30 mmol/L.

Ninety participants completed the study: 44 (85%) in the intensive target group and 46 (88%) in the standard target group. All were included in the primary intention-to-treat analysis. Participants were mostly men with an average age of 61. Average period of disease was 19 years and about half had a gout flare in the 3 months before enrollment in the study.

Fewer in Intensive Group Hit Target

The researchers found that serum urate at year 2 was significantly lower in the intensive target group, compared with the level in the standard target group (P = .002), but fewer participants in the intensive group hit their target, compared with those in the standard group (62% vs. 83%; P < .05).

The intensive group also required more medication. Participants in that group needed higher doses of the first-line treatment allopurinol (mean, 746 mg/day vs. 496 mg/day; P < .001). They also used more combination therapy (P = .0004).

Bone erosion scores were slightly better in both groups over 2 years, but there was no between-group difference (P = .20).

Rates of adverse and serious adverse events were similar between the groups.

The authors noted that a previous study has shown that escalating doses of allopurinol to achieve a target lower than 0.36 mmol/L (6.48 mg/dL) can reduce progression of bone erosion in gout.

“However, improved erosion scores were not observed in this study,” the authors noted.

The authors said that emerging data on intensive serum urate lowering “may lead to erosion healing in gout,” particularly with pegloticase (Krystexxa), a treatment that leads to profound reductions in serum urate.

They highlighted a small longitudinal study of patients treated with pegloticase in whom researchers observed the filling in of bone erosions over a year.

Pegloticase Not Available Outside United States

However, the authors explained, use of pegloticase is unlikely to be widespread for erosive gout because of its lack of availability outside the United States and the need for infusions every 2 weeks. Therefore, more feasible strategies are needed.

Guidelines suggest the serum urate target of less than 0.30 mmol/L (5.4 mg/dL) for people with severe gout, including those with chronic arthropathy.

Managing Gout Is a Long-term Process

Herbert S.B. Baraf, MD, a rheumatologist in a large group practice in the Washington, D.C., area and clinical professor of medicine at George Washington University, Washington, who was not part of this study, said he would not come to the conclusion that some cynics might draw that there’s no point in trying to continually lower uric acid.

“Managing gout is a long-term proposition, and the long-term benefit of continuous uric acid lowering continue to accumulate over a period of time,” Baraf said. He agreed with Dalbeth and colleagues that trying to get serum uric acid to less than 0.20 mmol/L is very difficult to achieve with oral drugs.

He said: “The study was not able to show a change in erosions because the amount of uric acid lowering wasn’t profound enough over a short enough period of time to show that, but over a longer period of time it might well show that.”

He said oral therapies work more slowly than enzyme-based therapies, such as pegloticase, but agreed there are barriers to using pegloticase.

“A drug like pegloticase costs about $26,000 per infusion every 2 weeks for a 6-month period. It’s not practical, and we tend to use it for people who are severely functionally impaired,” said Baraf.

It would still be a goal to keep the arthritis from progressing by using oral therapies, he said.

“I wouldn’t denigrate the fact that oral therapies are effective in decreasing flares over time, decreasing tophaceous deposits and probably – over a longer period of time allowing bone to heal. But 2 years is not enough time to show that.” He said showing benefit on erosions may take 5-10 years instead.

The study authors noted that the trial’s results “are not relevant to those without erosive disease, and to health care systems without access to a broad range of urate-lowering agents.”

Dalbeth reports personal fees (all less than $10,000) from AstraZeneca, Dyve BioSciences, Selecta, Arthrosi, Horizon, AbbVie, JW Pharmaceuticals, and PK Med outside the submitted work. The other authors have no disclosures. Gaffo reported no relevant financial relationships. Baraf has been an investigator/consultant and speaker for Horizon Therapeutics, maker of pegloticase; is an investigator and a consultant to Selecta Biosciences; and has been an investigator, speaker, and consultant for Takeda.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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