Epidemiology
The current prevalence of gout among adults in the United States is 3.9%, and there are approximately 8.3 million gout patients nationwide. The increase in the number of patients with gout is mainly related to the comorbidities that promote hyperuricemia: hypertension, obesity, metabolic syndrome, type II diabetes, increased prevalence of chronic renal insufficiency (CKD), as well as changes in dietary habits and increased use of thiazide diuretics and tab diuretics.
Commentary: The rising economy of developing countries such as China, the continuous improvement of living standards and changes in dietary structure are the main reasons for the increasing incidence of gout/hyperuricemia in recent years. In developed western countries such as the United States, where the economy has reached a relatively stable stage and the diet is basically in a “stable” state, co-morbidities that cause hyperuricemia and pharmacological factors may be the main factors contributing to the increasing prevalence of gout.
Patient education and management of comorbidities
Patient education, including dietary guidance, promoting a good lifestyle, and informing patients of the goals of treatment, as well as aggressive treatment of comorbidities that can lead to hyperuricemia, is a core component of treatment.
Commentary: Active and effective patient education is an important part of the treatment of chronic diseases. Data from epidemiological surveys at the European League Against Rheumatism (EULAR) conference showed that patients with gout have widespread misconceptions about the disease, lack knowledge about standardized uric acid-lowering therapy, and have poor medication compliance. Family physicians and non-rheumatologists also lack the concept of standardized treatment. Therefore, the Guidelines emphasize the importance of “education” and suggest that active control of co-morbidities that can lead to hyperuricemia is an important part of gout prevention and treatment, which deserves attention.
It is well established that severe drug rash associated with allopurinol is strongly associated with HLA-B*5801. In some Asian populations, it has been a medication concern for Asian gout patients because of the high positivity rate of this gene. As early as 2008, the local administration in Taiwan has issued a directive that this gene must be tested before taking allopurinol. However, the test is not widely available in Asian patients. This time, the “guideline” specifically emphasized the importance of HLA-B*5801 testing. The author’s research group successfully developed a method for rapid PCR testing of this gene a year ago and filed a patent for the invention, which is now in the process of being converted into a product.
The use of allopurinol should be started at a small dose for the following reasons: starting at a small dose reduces the possibility of triggering a gout attack; severe drug rash associated with allopurinol is related to the dose of the drug. 2010 edition of the Chinese Gout Guidelines also suggests that the dose should be started at 100 mg/d, but in practice, especially in primary care hospitals and non-specialist doctors, this point is often overlooked.
For patients who cannot “reach the target” even after using sufficient xanthine oxidase inhibitors, drugs that promote uric acid excretion can be combined, and this idea has been accepted earlier in China. However, it is worth noting which drugs to combine and when to start the combination. What is “adequate dose”? The author believes that it should be the maximum permissible dose contained in the drug’s instruction, but the possible adverse reactions at the maximum dose should be fully considered, and more caution should be exercised for patients with renal insufficiency.
Fenofibrate, coxsartan and other drugs were not originally used for uric acid-lowering treatment, but in the use of these drugs are found to be conducive to promoting the secretion of uric acid in the kidneys, so patients with hyperuricemia should give priority to these drugs when choosing lipid-lowering drugs and antihypertensive drugs. However, in patients with gout, these drugs are not recommended for uric acid-lowering therapy alone, but can be combined with xanthine oxidase inhibitors to improve the effect of uric acid-lowering therapy.
Most international gout treatment guidelines, including Chinese guidelines, suggest that uric acid-lowering therapy should be started only after the acute attack has subsided for at least 2 weeks, on the grounds that the use of uric acid-lowering therapy during an acute gout attack may aggravate the symptoms of gout. “The guidelines suggest for the first time that uric acid-lowering therapy is not contraindicated under the “protection” of effective anti-inflammatory drugs. This new view deserves to be confirmed in future clinical practice.
Uric acid excretory drugs
If monotherapy is used, probenecid is the drug of choice; fenofibrate and cloxacin have therapeutic uric acid lowering effects; uric acid excretory drugs are contraindicated as monotherapy in patients with a history of urinary stones; uric acid levels should be measured before the use of uric acid excretory drugs and should be followed up during treatment; adequate water intake, alkalinization of urine, and testing of urine pH should be ensured during treatment.
Commentary: The guideline does not consider uric acid-promoting drugs as the first choice, which is in line with the idea of starting at the source. However, some patients who do not respond to or tolerate xanthine oxidase inhibitors may still have the opportunity to use uric acid excretory drugs. For the reasons mentioned above, the use of benzbromarone is not recommended. The importance of alkalinizing the urine in the use of pro-uric acid excretory drugs is emphasized because more uric acid is excreted from the kidneys during drug use, and alkalinizing uric acid increases the amount of uric acid dissolved and may prevent deposition of urate crystals in the kidneys or the formation of stones. Measurement of uric acid plays an important role in the selection of this class of drugs and in evaluating the effectiveness of treatment. In normal people, uric acid is generally <600 mg/d. Pro-uric acid excretory drugs are suitable for those with low uric acid levels, but when uric acid is significantly increased, treatment with such drugs is not recommended.
Uric acid enzymes and combined medications
For patients with severe gout who are resistant or intolerant to conventional uric acid-lowering therapy, but there is a lack of consensus on how long the medication cycle should be. In patients with gout who are taking small doses of aspirin to prevent cardiovascular disease hazards, discontinuation is not required.
Commentary: Uric acidase can directly break down excess uric acid in the body and is a new option for gout uric acid lowering treatment. The drug is a biological agent, which is expensive, and its possible allergy and drug resistance are common features of biological agents, so it is recommended as a “second-line drug”. Small doses of aspirin can inhibit uric acid excretion by the renal tubules, which is thought to be an important cause of hyperuricemia. Previously, for gout patients taking aspirin in combination, doctors often recommended that patients take other anticoagulants as an alternative. “The guidelines suggest that for patients with gout, the negative effects of aspirin are negligible, so there is no need to discontinue or change medication.
Uric acid-lowering therapy in renal insufficiency
Thanks to Prof. Zou for his excellent answer: The 2012 “American College of Rheumatology Guidelines for the Treatment of Gout”, translated and reviewed by Prof. Zou, has been published in the Expert Lectures section of the Rheumatology and Immunology Channel.
In patients with grade 2-5 CKD or end-stage renal disease, if they have had a gout attack and are currently hyperuricemic, they should be treated with uric acid-lowering therapy; for the evaluation of renal insufficiency, Ccr is more important than creatinine; since there is no data on the safety of febuxostat in patients with grade 4 or higher CKD, propofol can be used as a first-line agent; for Ccr <50 ml/min. Probenecid alone is not recommended as a first-line drug.
Analysis: Renal insufficiency can be a complication of long-term gout on the one hand, and in addition, renal insufficiency caused by various renal diseases or systemic diseases can also lead to the occurrence of secondary gout. The treatment of uric acid reduction in patients with renal insufficiency has always been a difficult problem. The “guidelines” are very important for the prompting of medication for patients with renal insufficiency.
Blood uric acid monitoring
Blood uric acid monitoring is necessary for the treatment of gout. It is measured every 2-5 weeks during the adjustment of uric acid-lowering drugs. It should also be measured every 6 months after reaching the standard (blood uric acid <6mg/dl). The uric acid measurement is the basis for adjusting the dose of medication and is also useful for determining the patient's compliance with the treatment medication.
Commentary: The importance of monitoring blood uric acid during the treatment of gout patients has been generally recognized. However, the time interval for monitoring is not clearly defined. “The guideline clearly puts forward the periodicity of blood uric acid monitoring, especially the testing every 2-5 weeks during the use of uric acid-lowering drugs, which is consistent with the recommended adjustment of drug dose every 2-5 weeks.
Non-pharmacological treatment
Non-pharmacological treatment includes weight loss in obese individuals, trying to return to a normal body mass index (BMI), promoting a healthy diet, appropriate exercise, quitting smoking, and ensuring adequate water intake. See Table 1 for dietary recommendations.
Preventive medication for gout
Oral colchicine and low-dose NSAIDs are the first-line medications to prevent gout attacks. When starting uric acid-lowering drug therapy, colchicine 0.5 mg, qd or bid, or low-dose naproxen 250 mg, bid, in combination with a proton pump inhibitor is preferred. If these drugs are not effective, a low-dose glucocorticoid, prednisone Q10mg/d can be used. For those with signs of gout activity, the medication is continued for 6 months.
Signs of gout activity include.
①Gout stones found on physical examination;
②Recent acute gout attack;
(iii) chronic gouty arthritis and/or blood uric acid level not meeting the standard. Or for patients on uric acid-lowering therapy, continued medication until 3 months (for those without gout stones) or 6 months (for those with gout stones) after the blood uric acid standard is reached.
All of the above preventive drugs have also been used in the clinic in the past, but they are all significantly inadequate in terms of duration of therapy. The main reason for including glucocorticosteroids in the second-line prophylactic drugs is the potential adverse effects associated with long-term use of glucocorticosteroids.
In this article, the 2012 “American College of Rheumatology Guidelines for the Treatment of Gout” are interpreted and reviewed. It should be noted that developed countries have strict procedures and regulations in the process of guideline development, which are more scientific and of greater reference value, and are worthy of our reference in the development of our own guidelines. In the ACR guidelines, it is specifically mentioned that the “guidelines” do not recommend treatment for simple hyperuricemia due to the lack of information from randomized controlled studies, which fully demonstrates the objectivity and rigor of the “guidelines” formulation process. Of course, due to the differences in ethnicity, economic level, and available drugs, the US guidelines may not be fully suitable for the Chinese situation, and their rationality and scientific validity will be tested in future clinical practice.