Gout Treatment

Treatment for Acute Gouty Arthritis

• Therapeutic goal: Rapid alleviation of pain and inhibition of inflammation as quickly as possible after the onset of gout until after the attack is terminated (1-2 weeks)
• There is no single best agent for the treatment of a gout flare; NSAIDs Colchicine and corticosteroids are all effective 
• Specific anti-inflammatory treatment choices should be based upon patient factors (eg comorbidity, past experience, medication access) and contraindications

Long-term Treatment for Gouty Arthritis

Urate-Lowering Therapy

• Indications for initiation of therapy include the following:
  • Presence of tophaceous deposits, eg ≥1 subcutaneous tophi
  • Frequent and disabling attacks of gouty arthritis (≥2 attacks/year)
  • Clinical signs or radiographic damage attributable to gout
• May also be initiated in patients with history of >1 flare but have <2 flares per year and patients having their first flare and chronic kidney disease stage ≥3, serum urate level of >9 mg/dL or urolithiasis
• Therapeutic goal is to promote crystal dissolution and prevent crystal formation by maintaining the serum urate level at <6.0 mg/dL (<0.36 mmol/L)
• It is preferred to continue urate-lowering therapy indefinitely than to stop it if treatment is well tolerated
  • Urate-lowering therapy is a lifelong treatment and adjunctive lifestyle modification is important
• A treat-to-target strategy is recommended for patients on urate-lowering therapy wherein doses are adjusted based on serial serum urate levels in order to achieve a target level of <6.0 mg/dL (<0.36 mmol/L)
  • All patients on urate-lowering therapy should continue treatment to attain and maintain target level 
• On initiation of urate-lowering therapy, concomitant anti-inflammatory prophylaxis with NSAIDs, Colchicine or Prednisone/Prednisolone can be given and continued for at least 3-6 months, with ongoing evaluation and continuous prophylaxis for persistent flares

Treatment for Acute Gouty Arthritis

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Eg Indomethacin, Naproxen, Ibuprofen, Sulindac, Ketoprofen, Piroxicam, Tenoxicam
• Considered as one of the 1st-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
  • Relieve pain and reduce inflammation
• Proton pump inhibitors (eg Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole) or H₂ receptor blockers (eg Ranitidine, Famotidine) 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
  • Alternative treatment for those at risk of peptic ulcer disease or intolerant of non-selective NSAIDs
  • Similar cautions as for non-selective NSAIDs should be exercised in those with renal impairment, cardiac failure, hypertension and active peptic ulcer disease

Colchicine

• Considered as one of the 1st-line therapies for acute gouty arthritis especially as attack prophylaxis and for chronic kidney disease patients with proper dose adjustments
  • As effective as NSAIDs but slower in reducing severity of acute attack
• Alternative drug for those with contraindications to NSAIDs, including COX-2 inhibitors
• 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
  • Dose of 500 mcg 6-12 hourly has been recommended to prevent toxic side effects
• Lower dose regimen of Colchicine has comparable efficacy but fewer adverse events than higher dose regimen and is thus preferred
• Low doses may be used as prophylaxis against acute attacks during the initiation of urate-lowering therapy

Corticosteroids

• Considered as one of the 1st-line therapies for acute gouty arthritis
• 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
• May be given locally through intra-articular injection or systemically through oral or parenteral administration
  • 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
  • Safe and well-tolerated; side effects are are due to short courses
• Should not be given to patients with gouty arthritis who have concomitant septic arthritis

Biologic Interleukin-1 (IL-1) Inhibitors

• Eg Anakinra, Canakinumab
• Treatment option for patients with severe attacks of acute gouty arthritis refractory, intolerant or who have contraindications to other agents
• Anakinra provides relief of symptoms and is preferred for acute attacks because of its short half-life
• Canakinumab is a long-acting monoclonal antibody which can be considered in patients with history of multiple attacks refractory to other agents

Long-term Treatment for Gouty Arthritis 

Xanthine Oxidase Inhibitors

• Eg Allopurinol, Febuxostat
• Inhibit production of urate from hypoxanthine and xanthine
• Allopurinol is recommended as the 1st-line urate-lowering treatment for gout, including patients with chronic kidney disease stage ≥3 
  • Febuxostat, a 2nd-line option, may be substituted for Allopurinol if with treatment failure after upward dose titration with 1 xanthine oxidase inhibitor and/or drug intolerance 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 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
• Changing to an alternative oral urate-lowering therapy agent may be done in gout patients receiving Febuxostat with a history of cardiovascular (CV) disease or a new CV event 
• Allopurinol or Febuxostat is preferred over Probenecid in patients with chronic kidney disease 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 indicated and maximally tolerated dose who are not at serum urate target and/or have frequent gout flares (≥2 flares/year) or non-resolving subcutaneous tophi  

Uricosuric Agents

• Eg Probenecid, Sulphinpyrazone, Benzbromarone
• 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
  • May initiate treatment with low doses then subsequently titrate
• Probenecid and Sulphinpyrazone may be used as alternatives to Allopurinol in patients with normal renal function but not in patients with concomitant urolithiasis
• Benzbromarone may be used in patients with mild to moderate renal insufficiency
  • Small risk of hepatotoxicity should be considered

Uricolytic Agent

• Eg Pegloticase
• 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)
  • Severe chronic tophaceous gout with erosive joint involvement

Physical Treatments

• Rest and elevate the affected joint
• Hold bedclothes away from affected joint
• Apply ice pack and expose in a cool environment