With the improvement of people’s living standard, the prevalence of gout is increasing year by year, and the number of patients with refractory gout is also increasing. Patients with refractory gout have difficulty in reaching the standard blood uric acid level, and have recurrent arthritis attacks that do not respond well to conventional analgesics, and are often associated with gout stone formation, joint deformity, renal insufficiency, hypertension, diabetes and coronary heart disease, which cause great pain to patients and affect their quality of life and life expectancy.
The longer the duration of the disease and the more gout stones in the body, the longer the duration of uric acid reduction may be. For general gout, the ideal blood uric acid target value is <6mg/dl (360umol/L), while for refractory patients, it should be below 4mg/dl.
This may provide the following benefits to the patient:
(1) Less frequent acute attacks of arthritis.
(2) Fast dissolution of gout stones. The blood uric acid level is linearly and negatively correlated with the rate of uric acid stone dissolution, and the standard treatment helps the rapid dissolution of gout stones.
(3) It helps to slow down the progression of renal insufficiency.
(4) Improve the prognosis of patients with combined heart failure.
For patients with refractory gout, non-pharmacological therapy should be emphasized first and 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 urine (maintaining the urine pH at 6.2~6.8), etc.
Refractory gout drug treatment.
1. Allopurinol tablets
Start with low doses such as 50~100mg/d (reduces the risk of fatal allergy syndrome) up to 800~900mg/d.
2.Benzbromarone
If patients with refractory hyperuric acid can increase the dose beyond the prescribed dose under the supervision of the doctor, the same satisfactory effect can be achieved.
3. advocate the use of “one arrow, two (three) eagles” drugs
Clofentezan 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 anti-inflammatory properties without inducing acute attacks of gout, which are suitable for gout patients with combined hypertension and hypertriglyceridemia respectively. Atorvastatin can lower the blood cholesterol level and inhibit uric acid synthesis at the same time, which is suitable for gout patients with combined hypercholesterolemia.
For patients with ineffective or inefficient single medication, the combination of medication can be used to improve the effect of uric acid reduction.
For example, allopurinol (200~600mg/d) and benzbromarone (100mg/d) or propoxur (0.5g/d) at stable doses are significantly more effective than single drugs.
5.New uric acid-lowering drugs
(1) Inhibit uric acid synthesis new drug – febuxostat. It is especially suitable for patients with urinary stones that cannot be fully hydrated, excessive uric acid production, contraindication 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 patients with refractory gout for whom traditional uric acid-lowering therapy is ineffective.
In conclusion, refractory gout is more difficult to treat, and the sooner uric acid control is achieved and the more consistently it is achieved, the better the prognosis, and sustained achievement of uric acid 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 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 improve patient compliance.