Treatment of chronic gout

Around 60% of the patients with an acute gout attack will experience another attack within 12 months. Therefore where possible, correct any exacerbating factors should begin after the first gout attack (1):

• consider stopping, reducing or substituting diuretic treatment
• reconsider aspirin therapy
• reduce alcohol intake
• reduce intake of purine-rich foods

The main aim of treatment of chronic gout is to maintain the plasma urate levels below, < 6 mg/dl (< 360 micromol/l) in order to prevent acute flares, prevent development of tophi, help dissolve tophi, prevent the development of chronic gouty arthropathy (2)

• aim for a target serum urate level below 360 micromol/litre (6 mg/dl)
• consider a lower target serum urate level below 300 micromol/litre (5 mg/dl) for people with gout who:
  • have tophi or chronic gouty arthritis
  • continue to have ongoing frequent flares despite having a serum urate level below 360 micromol/litre (6 mg/dl)

There are two classes of drugs which reduces urate levels (3):

• the xanthine oxidase inhibitor - allopurinol and febuxostat
  • reduces the synthesis of uric acid
  • initial long-term treatment of recurrent uncomplicated gout normally should be with allopurinol
• uricosuric agents - probenecid, sulfinpyrazone, benzbromarone
  • increase urinary excretion of uric acid
  • used as second-line drugs in patients who are under-excretors of uric acid and in those resistant to or intolerant of allopurinol
  • relatively contraindicated in patients with nephrolithiasis and ineffective in the presence of renal insufficiency.
  • can be use together with allopurinol or febuxostat (3)

For patients who have refractory gout and/or resistant tophaceous disease, pegloticase is another treatment option (3).

Optimal use of urate-lowering therapies (ULTs) (4)

• allopurinol is the recommended first-line ULT to consider. It should be started at a low dose (50-100 mg daily) and the dose then increased in 100 mg increments approximately every 4 weeks until the sUA (serum uric acid) target has been achieved (maximum dose 900 mg)
  • in patients with renal impairment, smaller increments (50 mg) should be used and the maximum dose will be lower, but target urate levels should be the same
• febuxostat can be used as an alternative second-line xanthine oxidase inhibitor for patients in whom allopurinol is not tolerated or whose renal impairment prevents allopurinol dose escalation sufficient to achieve the therapeutic target
  • start with a dose of 80 mg daily and, if necessary, increase after 4 weeks to 120 mg daily, to achieve therapeutic target
• colchicine 0.5mg bd or od should be considered as prophylaxis against acute attacks resulting from initiation or up-titration of any ULT and continued for up to 6 months
  • in patients who cannot tolerate colchicine, a low-dose NSAID or coxib, with gastroprotection, can be used as an alternative providing there are no contraindications

Notes:

• febuxostat
  • NICE have stated that febuxostat is an option for the management of chronic hyperuricaemia in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated (6)
  • undergoes hepatic metabolism and does not require dose reduction in patients with renal impairment

Reference:

• (1) Eggebeen AT. Gout: an update. Am Fam Physician. 2007;76(6):801-8.
• (2) NICE (June 2022). Gout: diagnosis and management
• (3) Hamburger M. 2011 Recommendations for the diagnosis and management of gout and hyperuricemia. Postgrad Med. 2011;123(6 Suppl 1):3-36
• (4) Hui M et al. for the British Society for Rheumatology Standards, Audit and Guidelines Working Group, The British Society for Rheumatology Guideline for the Management of Gout, Rheumatology (2017), 56 (7): 1056-1059, https://doi.org/10.1093/rheumatology/kex150
• (5) Baker JF, Schumacher HR. Update on gout and hyperuricemia. Int J Clin Pract. 2010;64(3):371-7.
• (6) NICE (December 2008). Febuxostat for the management of hyperuricaemia in people with gout.