The incidence of gouty arthritis is increasing year by year, and the standardized treatment of hyperuricemia and gouty arthritis is receiving more and more attention. 2012 American College of Rheumatology (ACR) has developed the latest guidelines for the treatment of gout based on the consensus on diagnosis and treatment introduced in 2011, which is divided into two parts: the first part is the guidelines for the systemic treatment of gout, and the second part is the acute gouty arthritis The second part is the treatment of acute gouty arthritis and prophylactic anti-inflammatory therapy. This treatment guideline summarizes and updates past treatment guidelines from various countries, and combines the latest evidence from the literature and expert consensus to develop treatment protocols with different levels of evidence.
Non-pharmacological treatment of gout
The guidelines first emphasize the importance of patient education, and that diet and lifestyle interventions alone can go some way to lowering uric acid and/or preventing acute gouty arthritis attacks.
Regarding dietary control, the guidelines recommend.
① Limit the intake of large amounts of purine-rich foods in a short period of time, limit the intake of purine-rich meat, seafood and fructose drinks, and recommend low-fat or nonfat dairy products and vegetables;
② Reduce alcohol intake (especially beer, liquor and spirits), avoid alcohol abuse, and abstain from alcohol in patients with active disease, especially in patients with chronic gouty arthritis whose disease progression cannot be effectively controlled by medication.
Uric acid-lowering therapy (ULT)
Non-pharmacologic treatment is indicated for all patients. Those with blood uric acid (SUA) >7 mg/dl despite non-pharmacologic treatment should be given drugs. The ULT goal for patients with gout is SUA <6 mg/dl; for patients with prolonged unremitting gouty arthritis symptoms or gout stones, SUA should be <5 mg/dl.
Xanthine oxidase inhibitors (XOI), which inhibit uric acid production, are recommended as the drug of choice, and allopurinol or febuxostat monotherapy is recommended. Those who are contraindicated or intolerant to XOI may switch to a pro-uric acid excretory agent, but it is not recommended for those with creatinine clearance (CCr) <50 ml/min. Note that the CCr is monitored here and not the blood creatinine concentration (SCr).
In contrast to conventional wisdom, the guidelines state that ULT may be initiated after appropriate anti-inflammatory therapy during an acute gouty arthritis flare-up. this view has yet to be confirmed by extensive clinical data in China.
Allopurinol regimen Recommended initial dose ≤100 mg/d (50 mg/d in chronic kidney disease stage 4 and above); taper every 2-5 weeks; maintain maximum therapeutic dose (>300 mg/d) to bring SUA below target value; renal insufficiency can be treated at this dose as long as they are adequately educated and regularly monitored for drug toxicity reactions; screening for human leukocyte antigen (HLA)-B* is recommended prior to dosing. 5801 genotype.
Studies have confirmed that the frequency of HLA-B*5801 gene is higher in Han Chinese population and that positivity for this gene is one of the risk factors for allopurinol allergy, so screening for it may be an effective means to prevent allopurinol allergy in China. The maximum doses of allopurinol and febuxostat recommended by the U.S. Food and Drug Administration (FDA) are 800 mg/d and 80 mg/d, respectively. Considering the global application of the guidelines, the maximum dose of febuxostat is hereby adjusted to 120 mg/d.
The first choice for monotherapy is propofol, others include fenofibrate and cloxacin; a history of urinary calculi is a contraindication to these drugs; propofol should not be used as a first-line drug if the CCr is <50 ml/min; urinary acid concentration should be monitored before and during administration; prevention of urinary calculi formation by increasing fluid intake, alkalinizing the urine and monitoring urinary pH.
If SUA is not achieved after monotherapy, the guidelines also recommend a combination oral ULT program, such as an XOI drug in combination with a uric acid excretory drug. For patients with severe gout, refractory gout or gout that cannot tolerate oral uric acid-lowering drugs, pegloticase can be used. pegloticase has been shown to not only dissolve gout stones, but also improve the signs and symptoms of chronic gouty arthritis, but it is not recommended as a first-line drug.
Long-term maintenance therapy after achieving the blood uric acid standard
Long-term maintenance treatment regimens after SUA compliance include
① Prophylactic anti-inflammatory therapy (see Part II for details);
② Regular monitoring of SUA and adverse drug reactions;
③ After the disappearance of gout symptoms and signs, all treatments (including diet, lifestyle interventions and medication) should be continued to ensure that the SUA is maintained below the target value in the long term.
Treatment of acute gouty arthritis with prophylactic anti-inflammatory therapy
Basic principles of treatment for acute gouty arthritis flare-ups
Acute gouty arthritis attacks must be treated with medication, preferably starting within the first 24 hours of onset. If an acute gouty arthritis attack occurs during the course of ULT, uric acid-lowering medication must not be suspended. The principles of medication selection are shown in Table 1.
The guidelines emphasize the importance of patient education to let patients know what triggers an acute attack of gouty arthritis and that once an attack occurs, patients should know the basic principles of management; in addition, patients should be made aware that gout is the result of excessive accumulation of uric acid in the body and that only with effective ULT can the desired outcome be achieved.
Acute gouty arthritis drug treatment
NSAID use The NSAID should be taken in the full dose approved by FDA or European Medicines Agency (EMA). Cyclooxygenase 2 (COX-2) inhibitors, such as celecoxib, may be used when conventional NSAIDs are not tolerated or are contraindicated, but some experts have pointed out that the risk-benefit ratio of COX-2 inhibitors for acute gouty arthritis is not clear and should be applied with caution.
Patients must remain on NSAIDs until the acute arthritic episode is completely resolved. Patients with other concurrent diseases or hepatic or renal impairment should reduce the dosage as appropriate.
Colchicine use Guidelines recommend that colchicine be administered within 36 hours of an attack. In view of its significant adverse effects, low-dose therapy is currently preferred, i.e., a starting dose of 1.2 mg, followed by 0.6 mg 1 hour later, and 12 hours later by prophylactic anti-inflammatory therapy (0.6 mg qd or 0.6 mg bid) until complete resolution of symptoms. The dose must be reduced in patients with moderate or severe renal insufficiency.
Glucocorticosteroids are recommended for the control of acute gouty arthritis symptoms. Intra-articular injections may be given for one or two large joints, oral prednisone may be given for multiple joints or for joints not suitable for intra-articular injections, and intravenous or intramuscular methylprednisolone may be given for those who cannot take oral prednisone.
The guidelines for acute gouty arthritis where initial treatment is ineffective define suboptimal outcome as <20% improvement in VAS within 24 hours or <50% improvement in VAS after 24 hours. At this point, the correct diagnosis of acute gouty arthritis should be considered; if the diagnosis is correct, a switch to another class of monotherapy or the addition of a drug combination may be attempted. Trials of biologic agents have been initiated for the treatment of refractory gouty arthritis, but the efficacy of interleukin 1 inhibitors has not been unanimously confirmed by experts.
Adverse drug events The guidelines emphasize the need to be aware of increased drug toxicity due to co-morbidities or drug-drug interactions. For example, in patients with gout with moderate or severe renal insufficiency or liver disease, attention should be paid to the toxicity of NSAIDs, COX-2 inhibitors or colchicine; in patients with peptic ulcer, infection or diabetes, attention should be paid to the adverse effects of glucocorticoids; when anticoagulation or anti-platelet aggregation therapy is given, and then NSAIDs should be used with attention to drug-drug interactions.
Prevention of acute gout attacks
The guidelines emphasize that if ULT is initiated, appropriate anti-inflammatory therapy must be administered to prevent a reoccurrence of gouty arthritis during the decline in SUA. Oral colchicine (0.5 mg or 0.6 mg bid or qd, reduced as appropriate for renal impairment) or oral low-dose NSAIDs are preferred for attack prevention, and low-dose prednisone or prednisolone (≤10 mg/d) may be considered when contraindicated or intolerant to these drugs.
Regarding the timing of dosing, the guidelines state that prophylactic anti-inflammatory therapy should be administered whenever there are signs of disease activity. Patients should be medicated if they have gout stones, have had a recent acute gout attack, have chronic gouty arthritis, or are unable to achieve target SUA concentrations; there is no consensus on the specific dosing time frame.
Summary
The 2012 ACR guidelines are crucial to standardize gout treatment. They emphasize the importance of achieving SUA targets to prevent acute attacks of gouty arthritis, and propose the combination of NSAID and colchicine or colchicine and glucocorticoids for refractory gouty arthritis, and newer drugs such as febuxostat can be tried for hyperuricemia in which conventional uric acid-lowering drugs are ineffective.