Updated gout guidelines: Don’t let kidney function dictate allopurinol dosing



– Soon-to-be-published gout guidelines from the American College of Rheumatology will recommend dosing allopurinol above 300 mg/day to get serum urate below 6 mg/dL, even in people with renal impairment.

Dr. Tuhina Neogi, professor of medicine, Boston University M. Alexander Otto/MDedge News

Dr. Tuhina Neogi

It’s the same strong treat-to-target recommendation the group made in its last outing in 2012, but “we now have more evidence to support it,” said co–lead author, rheumatologist, and epidemiologist Tuhina Neogi, MD, PhD, a professor of medicine at Boston University.

She gave a sneak preview of the new guidelines, which will be published in 2020, at the ACR annual meeting. They are under review, but she said the “major recommendations will remain the same.”

“There will still be controversy that we have not yet proven that a threshold of 6 mg/dL is better than a threshold of 7 mg/dL, but we know that” at physiologic pH and temperature, monosodium urate starts to crystallize out at 6.8 mg/dL. “Serum urate is not a perfect measure or total body urate, so we need to get urate to below at least 6 mg/dL,” she said, and perhaps lower in some.

A popular alternative in primary care – where most gout is managed – is to treat to avoid symptoms. It “has no evidence,” and people “end up getting tophaceous gout with joint destruction. Suppressive colchicine therapy does not manage underlying hyperuricemia,” Dr. Neogi said.

With the symptom approach, “patients are often [profoundly] dismayed” when they find out they have large tophi and joint damage because they weren’t managed properly. “Primary care physicians [don’t often] see that because those patients don’t go back to them,” she said.

Dr. Neogi suspects that, for rheumatologists, the biggest surprise in the new guidelines will be a deemphasis on lifestyle and dietary factors. They can be triggers, but “gout is increasingly recognized as largely genetically determined,” and the impact of other factors on serum urate is low. Plus, “patients are embarrassed” by gout, and even less comfortable being honest with physicians “if they think we are blaming them,” she said.

The new document will recommend allopurinol as the definitive first-line option for hyperuricemia. Febuxostat (Uloric) was put on pretty much equal footing in 2012, but now “we acknowledge” that allopurinol dosing in head-to-head trials – 300 mg/day or 200 mg/day with renal impairment – was too low for most people, “so to say febuxostat is equivalent or superior isn’t really fair.” The substantially higher cost of febuxostat was also taken into consideration, she said.

The ACR will broaden the indications for urate lowering beyond frequent flares, tophi, and radiologic joint damage to include conditional, shared decision-making recommendations for people who have less than two flares per year, those with kidney stones, and people with a first flare if they are particularly susceptible to a second – namely those with serum urate at or above 9 mg/dL and people with stage 3 or worse chronic kidney disease, who are less able to tolerate NSAIDs and colchicine for symptom treatment.

The group will also relax its advice against treating asymptomatic hyperuricemia. Febuxostat trials have shown a reduction in incident gout, but the number needed to treat was large, so the ACR will recommend shared decision making.

Inadequate allopurinol dosing, meanwhile, has been the bête noire of rheumatology for years, but there is still reluctance among many to go above 300 mg/day. Dr. Neogi said it’s because of a decades-old concern, “unsupported by any evidence, that higher doses may be detrimental in people with renal insufficiency.” It’s frustrating, she said, because “there is good data supporting the safety of increasing the dose above 300 mg/day even in those with renal impairment,” and not doing so opens the door to entirely preventable complications.

As for allopurinol hypersensitivity – another reason people shy away from higher dosing, especially in the renally impaired – the trick is to start low and slowly titrate allopurinol up to the target urate range. Asian and black people, especially, should be screened beforehand for the HLA-B*58:01 genetic variant that increases the risk of severe reactions. Both will be strong recommendations in the new guidelines.

Dr. Neogi didn’t have any relevant industry disclosures.

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