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Caveat on urate levels

• Serum uric acid level may be normal at the time of an acute attack.

• Normal level does not rule out gout.

• May be better to recheck the level after 2 weeks

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Resolve the acute flare rapidly

• NSAIDs• Corticosteroids• Colchicine

Remember that above may all be limited by comorbidities !!

Antiinflammatories do not treat the underlying disease.

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Long term approach

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Allopurinol

• Purine “backbone” xanthine oxidase inhibitor• FDA approved in 1966, most widely used urate-

lowering drug for the last four decades.• Basis for the 1988 Nobel Prize in Physiology and

Medicine.• Starting dose of 50-100mg daily and slowly titrate;

consider prophylaxis against flare.• Some studies suggested that only 21% of patients on

300mg achieved urate level < 6.0.

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New and Emerging Gout Meds

• febuxostat– oral nonpurine xanthine oxidase inhibitor FDA approved in 2009 for gout and hyperuricemia

• pegloticase – PEGylated uricase; not yet FDA approved-- for advanced tophaceous gout, administered intravenously.

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Febuxostat

• FDA approved doses are 40mg and 80mg.

• Published RCT looked at higher doses as well.

• Compared to allopurinol, was as good or superior in achieving goal of sUA <6.0.

• Significant reduction in gout flares and tophi when sUA goal is maintained.

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Febuxostat

A

Allopurinol has a purine backbone.

Febuxostat is a non-purine xanthine oxidase inhibitor.

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Febuxostat

• Primarily excreted by the liver, only 3% by the kidney; no dosage reduction required for renal impairment.

• Mild transaminase elevations observed, similar to that of allopurinol.

• Contraindicated with use of 6-MP, azathioprine, theophylline

• In RCT a higher rate of CV and thromboembolic events noted (0.14 / 100 pt-years > allopurinol), but a causal relationship not identified

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Febuxostat

• Primarily excreted by the liver, only 3% by the kidney; no dosage reduction required for renal impairment.

• Mild transaminase elevations observed, similar to that of allopurinol.

• Contraindicated with use of 6-MP, azathioprine, theophylline

• In RCT a higher rate of CV and thromboembolic events noted (0.14 / 100 pt-years > allopurinol), but a causal relationship not identified

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Febuxostat

• In general 40mg (starting dose) not inferior to 300mg allopurinol. 80 mg dose produced higher rate of achieving target sUA level of <6.0 and reduction of flares

• 5-year findings (FOCUS) showed sustained effect with maintenance of sUA < 6.0 and nearly complete suppression of flares

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References (febuxostat)

• Becker, M.A., et al. NEJM.353:2450, December 8, 2005 {“FACT trial”}

• Schumacher, H.R., et al. Rheum. 48; (2),188- 194. {“FOCUS” 5-year findings}

• Becker, M.A, et al. Arthr & Rheum, 52; (3), 916-923.• Schumacher, H.R., et al. A&R (Arthr Care &

Research). 59; (11), 1540-1548.

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Thank you !!