The incidence of gouty arthritis is increasing year by year, and the standardized treatment regarding hyperuricemia and gouty arthritis is receiving increasing attention. 2012 the American College of Rheumatology (ACR) 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 a guideline for the systemic treatment of gout, and the second part is the acute gouty arthritis treatment and prophylactic anti-inflammatory therapy, both published in the journal Arthritis Care and Research [ArthritisCareRes2012, 64(10): 1431 and 1447]. This treatment guideline summarizes and updates past national treatment guidelines, incorporating the latest evidence from the literature and expert consensus to develop treatment protocols with different levels of evidence.
Principles of non-pharmacological and pharmacological treatment of gout
Non-pharmacologic treatment of gout
The guidelines first emphasize the importance of patient education, and that diet and lifestyle interventions alone can go some way toward 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 fat-free 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-pharmacological treatment is indicated for all patients. Those with blood uric acid (SUA) >7mg/dl despite non-pharmacological treatment should be given drugs. The ULT goal for gout patients is SUA <6mg/dl; for patients with prolonged unremitting gouty arthritis symptoms or gout stones, SUA should be <5mg/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 can be switched to pro-uric acid excretory agents, but they are not recommended for those with creatinine clearance (CCr) <50 ml/min. Note that CCr and not blood creatinine concentration (SCr) is monitored here.
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 is yet to be confirmed by extensive clinical data in China.
The recommended initial dose of allopurinol regimen is ≤100mg/d (50mg/d for those with chronic kidney disease stage 4 and above); gradually increase the dose every 2-5 weeks; maintain the maximum therapeutic dose (>300mg/d) to bring the SUA down below the target value; people with renal insufficiency can also be treated at this dose as long as they are adequately educated and regularly monitored for drug toxicity reactions; it is recommended to screen for human leukocyte antigen ( HLA)-B*5801 genotype before drug administration. Studies have confirmed that the frequency of HLA-B*5801 gene is higher in Han Chinese population and that positive 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.
Uric acid excretory drug regimen monotherapy is preferred to probenecid, others include fenofibrate and coxsartan; history of urinary stones is a contraindication to these drugs; probenecid should not be used as first-line drug when CCr<50ml/min; uric acid concentration in urine must be monitored before and during drug administration; prevention of urinary stone formation by increasing fluid intake, alkalinizing urine and monitoring urine pH.
If SUA is not achieved after monotherapy, the guidelines also recommend a combined 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);
Regular monitoring of SUA and adverse drug reactions;
③After the disappearance of gout symptoms and signs, all therapies (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 drug 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 caused by excessive accumulation of uric acid in the body, and that only effective ULT can achieve the desired outcome.
Acute gouty arthritis drug treatment
The use of NSAID should follow the FDA or European Medicines Agency (EMA) approved dosage in full. 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.
Guidelines for the use of colchicine 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 a prophylactic anti-inflammatory treatment dose (0.6 mg qd or 0.6 mg bid) 12 hours later until complete resolution of symptoms. The dose must be reduced in patients with moderate or severe renal insufficiency.
Guidelines for the use of glucocorticoids recommend that glucocorticoids can be used to control symptoms of acute gouty arthritis. Intra-articular injections can be given to those with one to two large joints involved, oral prednisone can be given to those with multiple joints involved or whose joints are not suitable for intra-articular injections, and intravenous or intramuscular methylprednisolone can be given to those who cannot take oral prednisone (Table 2).
Poor outcome is defined in the guidelines for acute gouty arthritis where initial treatment is ineffective 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 event 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 administered with NSAIDs, attention should be paid 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 (0.5mg or 0.6mgbid or qd, reduced as appropriate for renal impairment) or oral low-dose NSAID is preferred for attack prevention. low-dose prednisone or prednisolone (≤10mg/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 given medication 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.