If gout is diagnosed, take a urate-lowering drug long term, bring blood uric acid below 360 µmol/L and keep it there

Cost

Allopurinol costs a few to a few dozen yuan a month. At first, blood uric acid is checked every few weeks to adjust the dose, and once stable, every few months. For the first 3 to 6 months you also take a second drug that prevents attacks. The hard part is that you have to keep taking it when nothing hurts.

What you get

A randomized controlled trial in 517 adults who had had an attack in the previous 12 months. One group was nurse-led: the nurse explained what the disease is and adjusted uric acid to the target according to the numbers. The other group saw a general practitioner as usual. At 2 years, the share whose blood uric acid fell to <360 µmol/L (6 mg/dL) was 95% versus 30%. The chance of reaching the target was 3.18 times that of the usual-care group (RR 3.18, 95% CI 2.42–4.18, this range is the confidence range of the number), P<0.0001. Secondary measures in year 2, such as attack frequency, tophi and quality of life, were also better than in the usual-care group. For each extra year of life adjusted for quality of life (quality-adjusted life year), the cost was £5,066. The same trial also had a follow-up study, in which questionnaires went to 438 people and 82% were returned. Both groups reported the number of attacks in the past 12 months. The median in the target-reached group was 0 attacks (the middle half of people fell between 0 and 0). In the usual-care group it was 1 (0–3), P<0.001. The range in parentheses is called the interquartile range. The share still taking urate-lowering drugs in the target-reached group was 1.19 times that in the usual-care group (adjusted RR 1.19, 1.09–1.30). The 2020 gout guideline of the American College of Rheumatology strongly recommends starting urate-lowering therapy for three kinds of people: those with tophi growing under the skin, those whose imaging shows gout has eaten defects into the bone, and those with ≥2 attacks a year. The approach is to monitor blood uric acid continuously and adjust the dose by the results until the target is reached, with a target of <6 mg/dL. Allopurinol is the first choice, including for people with stage 3 or higher chronic kidney disease, with a starting dose of ≤100 mg/day. When starting, give an anti-inflammatory preventive drug at the same time, for at least 3 to 6 months. The same guideline also cites a series of observed cases. These patients stopped the drug after long-term good control, and their blood uric acid stayed <7 mg/dL after stopping. Among them, only 13% (27/211) had no attack at all during the 5-year follow-up. On diet, people who limited or gave up alcohol had blood uric acid 1.6 mg/dL lower than those who did not, and one serving of beer raised blood uric acid by 0.16 mg/dL. Healthy eating, the Mediterranean diet and the DASH diet had smaller effects. There is disagreement about which urate-lowering drug to choose first. The American College of Rheumatology guideline strongly recommends allopurinol as the first choice, because at a full dose it works, is well tolerated, safe and cheap. It also conditionally suggests that people on febuxostat who have a history of cardiovascular disease or a new cardiovascular event switch to another drug if one is available. This recommendation matches the FDA's boxed warning on febuxostat. One basis is the CARES trial, in which 6,190 gout patients with cardiovascular disease were randomly given febuxostat or allopurinol. The risk of death from any cause in the febuxostat group was 1.22 times that of 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 reached a different conclusion. It enrolled 6,128 patients over 60 with cardiovascular risk factors, and febuxostat did not cause more major cardiovascular events than 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 drugs that make the kidneys excrete uric acid, the American College of Rheumatology conditionally advises against alkalinizing the urine, because there is no evidence it works, and the certainty of the evidence is very low. It also asks that these people be told to drink more water, and says people with known kidney stones or stage 3 or higher chronic kidney disease should not use this kind of drug.

Notes

Disputed: which drug to use to lower uric acid differs between countries' guidelines. The U.S. guideline puts allopurinol first, and people with cardiovascular disease should switch off febuxostat if they can, but the European FAST trial did not see febuxostat being more dangerous. Benzbromarone, a drug that makes the body excrete uric acid, can still be bought in China. The guidelines of the Chinese Medical Association (中华医学会) (2019 edition and the 2024 update) give separate recommendations on choosing a drug and on alkalinizing urine. Whether to add sodium bicarbonate to alkalinize urine when taking benzbromarone, the U.S. guideline says there is no evidence; follow your own doctor's advice, and don't skimp on water. Han Chinese people are worth testing for HLA-B*5801 before taking allopurinol. It is an inborn genotype that governs immune responses, and one test gives a result that never changes. The share carrying this gene is 7.4% among Han Chinese, Koreans and Thais, and only 0.7% among white and Hispanic people. After allopurinol, people of Asian and African descent have 3 times the risk of allopurinol hypersensitivity syndrome as white people, and in severe cases the skin peels off over large areas and it can be fatal. The American College of Rheumatology's 2020 gout guideline suggests that for these two groups, testing before starting the drug can be considered. Starting to lower uric acid actually makes attacks more likely, so the guideline clearly requires taking an anti-inflammatory preventive drug at the same time for the first 3 to 6 months. "It hurt more after I took the urate-lowering drug, so I stopped" is the most common way this goes wrong. When the pain comes, what to do is add the anti-inflammatory drug as your doctor says, not stop the urate-lowering drug. Different sources write the target differently: <6 mg/dL is about 360 µmol/L, and Chinese lab reports mostly use µmol/L. High uric acid found at a checkup with no attack ever is a different matter; see §6.19. For sugary drinks and alcohol, see §2.7, §2.19 (don't drink sugary drinks, drink little or no alcohol).

Evidence grade

A : Specific numbers from meta-analyses, large cohorts or randomized trials; for law and policy, the statute or official text.

Sources

1. Doherty M, Jenkins W, Richardson H, et al. (2018). Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial. Lancet, 392(10156), 1403-1412. https://doi.org/10.1016/S0140-6736(18)32158-5
2. Abhishek A, Jenkins W, La-Crette J, Fernandes G, Doherty M (2020). Nurse-led care is preferred over GP-led care of gout and improves gout outcomes: results of Nottingham Gout Treatment Trial follow-up study. Rheumatology, 59(3), 575-579. https://doi.org/10.1093/rheumatology/kez333
3. FitzGerald JD, Dalbeth N, Mikuls T, et al. (2020). 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care & Research, 72(6), 744-760. https://doi.org/10.1002/acr.24180
4. White WB, Saag KG, Becker MA, et al.; CARES Investigators (2018). Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. New England Journal of Medicine, 378(13), 1200-1210. https://doi.org/10.1056/NEJMoa1710895
5. Mackenzie IS, Ford I, Nuki G, et al.; FAST Study Group (2020). Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial. Lancet, 396(10264), 1745-1757. https://doi.org/10.1016/S0140-6736(20)32234-0
6. 中华医学会内分泌学分会 (2020). 中国高尿酸血症与痛风诊疗指南(2019). 中华内分泌代谢杂志, 36(1), 1-13. https://doi.org/10.3760/cma.j.issn.1000-6699.2020.01.001

Translated from the Chinese original. Original book, section 16, tip 9. This section is about health and medicines. It is general information, not a substitute for a doctor’s diagnosis or prescription. Content may be out of date and rules differ by place. When you actually deal with an agency, a doctor or a court, follow what local officials, doctors and lawyers tell you. Disclaimer