Gout Treatment
Principles of Therapy
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
Pharmacotherapy
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
Non-Pharmacological Therapy
Physical Treatments
- Rest and elevate the affected joint
- Hold bedclothes away from affected joint
- Apply ice pack and expose in a cool environment