For patients with refractory gout, the first thing to emphasize is non-pharmacological therapy, which should be used throughout the treatment, such as strict control of high purine diet, soft drinks and fructose, abstaining from beer and liquor, drinking more water (the amount of water should make the 24-hour urine volume exceed 2000ml) and alkalinizing the urine (maintaining the urine pH at 6.2~6.8). In addition, there are a number of points that need to be emphasized in drug therapy. However, most studies have shown that long-term low to medium doses of allopurinol do not reduce the incidence of lethal allergy syndrome and have poor uric acid-lowering efficacy. However, starting with low doses such as 50-100 mg/d and gradually increasing the dose may reduce the risk of fatal allergic syndrome up to 800-900 mg/d. At higher doses, the efficacy increases significantly without an increase in adverse effects. Similarly, other uric acid-lowering drugs such as benzbromarone can also be increased gradually from small doses on the basis of strict monitoring of adverse reactions, and the dose can eventually exceed the conventional dose in order to achieve the blood uric acid standard. 2, advocate the use of “a double (three) carved” drugs Many drugs can lower blood pressure, blood lipid and/or blood sugar at the same time can also lower blood uric acid, and have a “double” or even “a triple” effect. “Many drugs can lower blood pressure, blood lipids and/or blood glucose while also lowering blood uric acid. Clozaril and fenofibrate can lower blood uric acid by 15%-30% by promoting uric acid excretion while lowering blood pressure and triglycerides, respectively. They also have the advantages of increasing urinary pH without increasing urinary crystals and having anti-inflammatory properties without inducing acute gout attacks, which are suitable for gout patients with combined hypertension and hypertriglyceridemia, respectively. Atorvastatin can lower blood cholesterol level and reduce blood uric acid by 6.4%-8.2% by inhibiting uric acid synthesis, which is suitable for gout patients with combined hypercholesterolemia. In addition to lowering sugar and triglycerides, Arholofenate and Arholofenate can also reduce uric acid by 15%~29% by promoting uric acid excretion in a dose-dependent manner, which is suitable for gout patients with both diabetes and hyperlipidemia. 3, also to talk about the combination of drugs For patients with ineffective or poor efficacy of a single drug, the combination of drugs can be used to improve the effect of uric acid reduction. For example, the combination of allopurinol (200~600mg/d) and benzbromarone (100 mg/d), propoxur (0.5g/d) or RDEA594 (200~600mg/d, second generation uric acid excretory drug) at stable doses is significantly better than allopurinol alone in lowering uric acid. The combination of RDEA594 (600mg/d) and febuxostat (40~80mg/d) was also significantly better than febuxostat alone in lowering uric acid. Of course, there are other ways to combine drugs, such as between two drugs that inhibit uric acid synthesis. The combination of allopurinol (100-300 mg/d) with the purine adenosine phosphorylase inhibitor BCX4208 (20-80 mg/d) brought more gout patients to uric acid levels than allopurinol alone, and the rate of attainment increased with increasing doses of both drugs. These drugs can also be combined with drugs that have relatively weak uric acid-lowering effects. 4. Expectation for new uric acid-lowering drugs (1) New drug to inhibit uric acid synthesis – febuxostat. It is especially suitable for patients with urinary stones that cannot be fully hydrated, excessive uric acid production, contraindications to uric acid excretory drugs and allopurinol allergy or intolerance. (2) RDEA-594, a second-generation uric acid excretory agent, is characterized by minimal hepatotoxicity, is comparable to allopurinol in efficacy, is effective in mild to moderate renal insufficiency, has a very low risk of inducing kidney stones, and has no serious adverse events. (3) A new drug to promote uric acid decomposition – Precahi. This drug is fast in lowering uric acid and dissolving gout stones, and can be used in adult refractory gout patients for whom traditional uric acid-lowering therapy has failed. However, the high price, infusion reactions and frequent gout attacks during the initial period of use limit its widespread use. In conclusion, refractory gout is more difficult to treat. Regardless of which uric acid-lowering drug or drugs are used, the earlier the target is reached and the more consistently it is reached, the better the prognosis is, and sustained uric acid compliance is the key to refractory gout treatment. It is worth noting that in the early stage of uric acid-lowering treatment for refractory gout, acute attacks of gout need to be prevented. On the one hand, for the first time with uric acid-lowering drugs, the dose should be gradually increased from small doses; on the other hand, small doses of colchicine (0.5 mg, tid) or non-steroidal anti-inflammatory drugs can be used to prevent acute attacks, and biological agents including and anti-interleukin-1 and anti-tumor necrosis factor (TNF) alpha agents can be used for those who are ineffective to reduce the pain caused by joint attacks and to improve the patient’s compliance.