#262 Who let the Gout Out? Targeting Uric Acid Levels in Treating Gout
CLINICAL QUESTION
To prevent gout recurrence, should we dose urate lowering therapies (like allopurinol) to target uric acid levels?
BOTTOM LINE
Best evidence finds that increasing doses of allopurinol to achieve a specific serum urate target (example <360 μmol/L) does not reduce gout flares, pain, or function, compared to standard allopurinol dosing. Febuxostat increases cardiovascular and overall mortality and should not be used in most patients with gout.
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EVIDENCE
One randomized, controlled trial (RCT) evaluated 183 patients on allopurinol (mean dose ~270 mg/day) for gout with persistently elevated serum urate levels (mean 430 μmol/L) and more than 3 flares in the past year.1 Randomized to escalating allopurinol dose to achieve a target serum urate of <360 μmol/L or continue their current allopurinol dose. After 12 months:
- Mean daily allopurinol dose: 390 mg intervention, 290 mg control.
- ≥ 1 gout flare: 54% intervention, 59% control: not statically different.
- Intervention group achieved serum urate <360 μmol/L more often: 69% versus 32%.
- Tophi resolution, functional status, pain: no difference.
- No difference in serious adverse events, rash, or gastrointestinal complaints.
- 10 RCTs (6100 patients) of urate lowering therapies reported no relationship between patients achieving serum urate <360 μmol/L and gout flare risk.2
- Cohort studies of urate lowering therapies found an association between fewer gout flares and:
- An increased length of time a patient is on urate lowering therapies.
- Serum urate levels <360 μmol/L.
- Most guidelines3 recommend a “treat to target” strategy for serum urate levels, while a recent guideline4 concludes insufficient evidence to recommend “treat to target.”
- Compared to allopurinol, febuxostat increases:
- The proportion of gout flares (at up to one year):5 44% febuxostat versus 38% allopurinol; number needed to harm (NNH)=19.
- Cardiovascular death:6 4.3% versus 3.2% allopurinol, NNH=91.
- All-cause mortality:6 7.8% versus 6.4% allopurinol, NNH=72.
- Health Canada warns against febuxostat use in patients with cardiovascular disease.7
- Starting allopurinol and colchicine concurrently during a gout flare does not prolong or worsen flare.8
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lowering uric acid to target not necessary