After a gout diagnosis, if tophi have grown, imaging shows bone eaten out, or flares come 2 or more times a year, take a urate-lowering drug long term and hold serum urate under 360 µmol/L

If tophi have grown, bone has been eaten out, or flares come 2 or more times a year, take a urate-lowering drug long term and hold urate under 360 µmol/L. If flares are infrequent, whether to take it is something to settle with the doctor. Among patients whose dose a nurse adjusted from the lab results, 95% were at target after 2 years, and only 30% with usual care. After the target is reached the drug still cannot be stopped. Cutting foods lowers it only so much.

Cost

Allopurinol (别嘌醇) costs a few CNY to a few dozen CNY a month. At the start, check serum urate every few weeks to adjust the dose; once it is stable, every few months. For the first 3 to 6 months also take a drug that prevents flares. The hard part is keeping on with it when nothing hurts.

Benefit

A randomized controlled trial of 517 adults who had flared in the past 12 months. The nurse-led group had the disease explained, then had urate adjusted to target from the lab results. The other group had usual care from a general practitioner. At 2 years, the share with serum urate <360 µmol/L (6 mg/dL) was 95% versus 30%. The chance of reaching target was 3.18 times that of the usual-care group (RR 3.18, 95% CI 2.42–4.18, this interval is the confidence range of the figure), P<0.0001. In year 2, flare frequency, tophi, and quality of life, these secondary measures, were also better than in the usual-care group. Each extra year of life adjusted for quality of life (a quality-adjusted life year) cost £5066. The same trial also ran a follow-up: questionnaires went to 438 people and 82% came back. Both groups reported their own flare counts over the past 12 months. The median in the target group was 0 (the middle half of people fell between 0 and 0). Usual care was 1 (0–3), P<0.001. The range in those parentheses is called the interquartile range. The share still taking a urate-lowering drug was 1.19 times the usual-care group (adjusted RR 1.19, 1.09–1.30). The 2020 American College of Rheumatology gout guideline strongly recommends starting urate-lowering treatment for people with subcutaneous tophi, people whose imaging shows gout has eaten a defect into the bone, or people with ≥2 flares a year. For more than a single flare but fewer than 2 a year, the guideline conditionally suggests the drug; a conditional recommendation is settled between doctor and patient. For a first flare, it conditionally suggests not starting at once. The exception is chronic kidney disease of stage 3 or above, serum urate >9 mg/dL, or a past urinary stone; those are conditionally suggested to treat. The method is to keep watching serum urate and adjust the dose from the results until target, with a target <6 mg/dL. Allopurinol is the first choice, including for chronic kidney disease of stage 3 or above, at a starting dose ≤100 mg/day. At the start, also give an anti-inflammatory preventive drug for at least 3 to 6 months. The same guideline also cites a set of case observations. These patients stopped the drug after long good control, and after stopping, serum urate stayed <7 mg/dL. Among them, only 13% (27/211) had no flare at all over 5 years of follow-up. On diet, people who limited alcohol or stopped it had serum urate 1.6 mg/dL lower than people who did not limit it, and a serving of beer raised serum urate by 0.16 mg/dL. A healthy diet, a Mediterranean diet, and the DASH diet had smaller effects. Which urate-lowering drug to choose first is disputed. The American College of Rheumatology guideline strongly recommends allopurinol as the first choice, because at a high enough dose it works, is tolerated, is safe, and is cheap. It also conditionally suggests that a person on febuxostat (非布司他) who has a history of cardiovascular disease, or a new cardiovascular event, switch if another drug is available. That recommendation matches the boxed warning the FDA put on febuxostat. It draws on the CARES trial: 6190 gout patients with cardiovascular disease were randomized to febuxostat or allopurinol. All-cause death risk in the febuxostat group was 1.22 times the allopurinol group (HR 1.22, 95% CI 1.01–1.47, about 22% higher). Cardiovascular death was 1.34 times (1.03–1.73, about 34% higher). The European FAST trial came to a different conclusion. It enrolled 6128 patients aged over 60 with cardiovascular risk factors; major cardiovascular events on febuxostat were not higher than on allopurinol (HR 0.85, 0.70–1.03). Deaths were 7.2% in the febuxostat group and 8.6% in the allopurinol group. For people taking a drug that promotes uric acid excretion through the kidney, the American College of Rheumatology conditionally suggests not alkalinizing the urine, because there is no evidence that it works and the certainty of the evidence is very low. It also requires telling those people to drink more water. People with known kidney stones, or with chronic kidney disease of stage 3 or above, should not use this class of drug. The same guideline notes that the HLA-B\5801 genotype is most common in people of Han, Korean, and Thai ancestry, at 7.4%, in African Americans at 3.8%, and in white people and in Hispanic people at 0.7% each. For Asian people and African Americans taking allopurinol, the risk of allopurinol hypersensitivity syndrome is 3 times the risk in white people. The guideline conditionally suggests testing these groups for HLA-B\5801 before allopurinol; the certainty of the evidence is very low

Notes

Disputed: which drug to use to lower urate differs across national guidelines. The US guideline prefers allopurinol, and a person with cardiovascular disease should switch off febuxostat when another drug is available, but the European FAST trial did not find febuxostat more dangerous. Benzbromarone (苯溴马隆) can still be bought in China; it promotes uric acid excretion. The guidelines of the Chinese Medical Association (中华医学会) (the 2019 edition and the 2024 update) give separate recommendations on drug choice and on alkalinizing the urine. Whether to add sodium bicarbonate to alkalinize the urine while taking benzbromarone: the US guideline finds no evidence; follow the doctor; drinking more water cannot be skipped. **People of Han ancestry (汉族) should be tested for HLA-B\5801 before allopurinol. It is an inborn gene type that governs immune response, and a test result does not change for life. Carriers are 7.4% of Han, Korean, and Thai people, and only 0.7% of white and Hispanic people. After allopurinol, the risk of allopurinol hypersensitivity syndrome in Asian people and African Americans is 3 times the risk in white people; when the illness is severe, skin peels off over a large area and it can kill. The 2020 American College of Rheumatology gout guideline suggests that, for these groups, a test before the drug can be considered. Starting a urate-lowering drug makes a flare more likely at the beginning*, so the guideline explicitly requires an anti-inflammatory preventive drug at the same time for the first 3 to 6 months. "It hurt more after the urate-lowering drug, so I stopped" is a common way this fails. When it hurts, add an anti-inflammatory as prescribed; do not stop the urate-lowering drug. Targets are written differently: <6 mg/dL is about 360 µmol/L, and Chinese lab sheets mostly use µmol/L. High urate on a checkup, with no flare ever, is a different matter; see section 6, item 19. Sugary drinks and alcohol: see section 2, items 7 and 19 (do not drink sugary drinks; drink little or no alcohol). A large amount of meat and seafood at a meal, plus alcohol, can bring on a flare; see item 10 (at a barbecue or a group meal, do not eat a large amount of meat and seafood at a sitting)

Sources · 6

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