Gout Management

Treatment for Acute Gouty Arthritis

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Example drugs: Ibuprofen, Indomethacin, Ketoprofen, Naproxen, Piroxicam, Sulindac, Tenoxicam

Nonsteroidal anti-inflammatory drugs are considered as one of the first-line therapies for acute gouty arthritis. Fast-acting NSAIDs at maximum dose for short-term use are the oral drugs of choice for symptom relief in acute gouty arthritis, provided that there are no contraindications to their use. The goals are to relieve pain and to reduce inflammation. Proton pump inhibitors (eg Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole) or H₂ receptor blockers (eg Famotidine, Ranitidine) may help prevent the development of gastrointestinal ulcers in patients taking NSAIDs. Alternative drug therapy should be considered in patients with history of peptic ulcer disease, hypertension, renal impairment and cardiac failure. COX-2 inhibitors are an alternative treatment for those at risk of peptic ulcer disease or intolerant of non-selective NSAIDs. Similar cautions for non-selective NSAIDs should be exercised in those with renal impairment, cardiac failure, hypertension and active peptic ulcer disease.

Colchicine 







Colchicine is considered as one of the first-line therapies for acute gouty arthritis especially as attack prophylaxis and for chronic kidney disease (CKD) patients with proper dose adjustments. This is as effective as NSAIDs but slower in reducing the severity of an acute attack. This is an alternative drug for those with contraindications to NSAIDs, including COX-2 inhibitors. This is poorly tolerated by elderly due to gastrointestinal effects. High risk of toxicity with side effects (ie nausea, vomiting, abdominal pain, profuse diarrhea) more common in patients with impaired renal or hepatic function. The dose of 500 mcg 6-12 hourly has been recommended to prevent toxic side effects. A lower-dose regimen of Colchicine has comparable efficacy but fewer adverse events than a higher-dose regimen and is thus preferred.  Low doses of Colchicine for 3-6 months may be used as prophylaxis against acute attacks during the initiation of urate-lowering therapy.

Corticosteroids

Corticosteroids are considered as one of the first-line therapies for acute gouty arthritis. A short course can be considered in elderly people and those with renal insufficiency, hepatic dysfunction, cardiac failure, peptic ulcer disease and hypersensitivity/refractory to NSAIDs or Colchicine and other treatments. This may be given locally through intra-articular injection or systemically through oral or parenteral administration. Intra-articular injection may be used in patients with severe attacks affecting ≥1 joints, particularly large weight-bearing joints. Systemic corticosteroids may be used in patients with acute, severe and/or polyarticular attacks. Parenteral glucocorticoids are preferred over interleukin-1 (IL-1) inhibitors or adrenocorticotropic hormone (ACTH) when oral dosing is not possible. In those with monoarthritis, an intra-articular aspiration and intra-articular injection of long-acting corticosteroid are highly effective in terminating the attack. This is safe and well-tolerated; side effects are rare due to short courses. This should not be given to patients with gouty arthritis who have concomitant septic arthritis.

Biologic Interleukin-1 (IL-1) Inhibitors

Example drugs: Anakinra, Canakinumab

Biologic interleukin-1 (IL-1) inhibitors are treatment options for patients with severe attacks of acute gouty arthritis refractory, intolerant or who have contraindications to standard treatment agents (eg NSAIDs, Colchicine, and/or corticosteroids). This may be considered as a second-line treatment option for prophylaxis of gout in whom Colchicine or NSAIDs are contraindicated. Anakinra provides relief of symptoms and is preferred for acute attacks because of its short half-life; may be an option for patients with CKD. Canakinumab is a long-acting monoclonal antibody that can be considered in patients with history of multiple attacks refractory to other agents. This should be avoided in patients with active infection.

Long-term Treatment for Gouty Arthritis

Xanthine Oxidase Inhibitors 







Example drugs: Allopurinol, Febuxostat

Xanthine oxidase inhibitors inhibit production of urate from hypoxanthine and xanthine. Allopurinol is recommended as the first-line urate-lowering treatment for gout, including patients with CKD stage ≥3 or CVD. Febuxostat, a second-line option, may be substituted for Allopurinol if there is treatment failure after a maximally titrated Allopurinol dose and/or drug intolerance or contraindication to Allopurinol. Treatment should be initiated with low doses of Allopurinol and Febuxostat followed by subsequent titration. For patients taking Allopurinol, dose adjustment (start at lower dose) should be made for all patients especially those with renal impairment. Prior to the initiation of Allopurinol therapy, it is recommended that HLA-B*5801 screening be done especially in patients at high risk for severe Allopurinol hypersensitivity (AHS) reaction (eg Korean, Han Chinese, Thai). Allopurinol desensitization may be performed in patients with a prior Allopurinol allergic response who cannot be given other oral urate-lowering therapy and have a negative HLA-B*5801 test. Changing to an alternative oral urate-lowering therapy agent may be done in gout patients receiving Febuxostat with a history of CVD or a new CV event. Allopurinol or Febuxostat is preferred over Probenecid in patients with CKD stage ≥3. Changing to a second xanthine oxidase inhibitor over adding a uricosuric agent may be done in gout patients taking their first xanthine oxidase inhibitor at the indicated and maximally tolerated dose who are not at the serum urate target and/or have frequent gout flares (≥2 flares/year) or non-resolving subcutaneous tophi. Consider the addition of a uricosuric agent in patients with severe renal impairment.

Uricosuric Agents

Example drugs: Benzbromarone, Dotinurad, Probenecid, Sulphinpyrazone

Uricosuric agents enhance renal excretion of uric acid. Benzbromarone may be used in patients with mild to moderate renal insufficiency. A small risk of hepatotoxicity should be considered. Dotinurad is a selective uric acid reabsorption inhibitor indicated for the treatment of hyperuricemia with or without gout. Probenecid is an alternative urate-lowering treatment in cases where Allopurinol and/or Febuxostat is contraindicated or not tolerated, except in patients with creatinine clearance of <50 mL/min. Initiate treatment with low doses then subsequently titrate. This may be given in combination with Allopurinol in patients unable to achieve target serum uric acid level and with high CVD risk. Probenecid and Sulphinpyrazone may be used as alternatives to Allopurinol in patients with normal renal function but not in patients with concomitant urolithiasis.

Uricolytic Agent

Example drug: Pegloticase

A uricolytic agent is a polyethylene glycol conjugate that lowers uric acid levels by catalyzing the conversion of uric acid to the more water-soluble compound Allantoin. Pegloticase is recommended for adult patients with: Severe debilitating chronic tophaceous gout refractory and/or intolerant to conventional urate-lowering treatments; serum uric acid level not on target despite treatment with xanthine oxidase inhibitors, uricosuric agents and other interventions, and who have non-resolving subcutaneous tophi or frequent flares of gout (≥2 flares/year); and severe chronic tophaceous gout with erosive joint involvement. 

Patient Education

Patient education, appropriate lifestyle advice and shared decision-making are core aspects of management. This often improves the patient’s understanding and compliance when done at the start of therapy. Educate the patient regarding the disease, its treatment options, duration and side effects, and associated comorbidities. Give advice on possible changes in life habits that can lead to an improvement in the overall metabolic profile of the patient. Patients should be made to understand that genetics contribute to risk factors more than indulgent food and drinks, therefore the need for urate-lowering therapy may be long-term.

Lifestyle Modification

The goal of lifestyle modification is to help prevent both gouty attacks and complications, together with its comorbidities. It is a part of the long-term management of gout.

Body Mass Index (BMI)

The aim is to have ideal body weight through gradual weight loss (0.5-1 kg/week), with gradual caloric restriction and regular exercise. Avoid “crash dieting” and high-protein/low-carbohydrate diets since these may cause ketosis and result in hyperuricemia. Daily or at least 45-minute, 4-times-a-week, low-impact (eg walking, biking, swimming) or aerobic exercise is recommended.

Dietary Management

Dietary restriction can decrease the occurrence of gouty attacks but has little role in lowering serum urate levels in patients with gout. Reduce the intake of meat (eg beef, lamb, pork). High intake of high-fiber fruits, vegetables, nuts, legumes, vegetable protein reduces the risk of gout (lower serum uric acid). Consumption of low-fat dairy products or skim milk up to two servings daily. Limit sugar-sweetened softdrinks and beverages containing fructose. Evidence is insufficient to recommend for or against limiting intake of purine-rich food (eg brain, liver, kidney, anchovies, sardines, mackerel, seafood, shellfish) in preventing gout flares or reducing serum uric acid levels. 

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Alcohol Intake

Restrict alcohol consumption to <21 units/week for men and 14 units/week for women. Have at least three alcohol-free days/week. Avoid alcohol intake when suffering from frequent gout attacks or when gout symptoms are poorly controlled.

Smoking

Complete cessation of smoking is recommended.

Adequate Fluid Intake 

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The recommended fluid intake is 2-3 L/day. Restrict fluid intake in some patients (eg with heart failure or severe renal insufficiency).

Physical Treatments

Rest and elevate the affected joint. Hold bedclothes away from the affected joint. Apply an ice pack to the affected joint and expose it to a cool environment.