A 59-year-old man is evaluated for a 6-month history of gout. He was doing well on colchicine and allopurinol but developed hypersensitivity to allopurinol, which resolved with cessation of the agent. He then began to have more frequent gout flares; two flares occurred in the past month and were treated with prednisone. History is also significant for hypertension, chronic kidney disease, and dyslipidemia. Current medications are colchicine, lisinopril, metoprolol, and simvastatin.
On physical examination, temperature is 37.2 °C (98.9 °F), blood pressure is 142/86 mm Hg, pulse rate is 64/min, and respiration rate is 12/min. BMI is 30. The remainder of the examination is normal.
Laboratory studies reveal a serum creatinine level of 2.3 mg/dL (203.3 µmol/L), a serum urate level of 9.2 mg/dL (0.54 mmol/L), and normal liver chemistry studies; estimated glomerular filtration rate is 48 mL/min/1.73 m2.
Which of the following is the most appropriate next step in management?
A: Discontinue colchicine
B: Start febuxostat
C: Start pegloticase
D: Start probenecid
MKSAP Answer and Critique
The correct answer is B: Start febuxostat.
Febuxostat is indicated for this patient with frequent gout attacks. He had been taking allopurinol, a first-line agent for serum urate reduction in patients with gout. Urate-lowering therapy is indicated for patients with gout who experience repeated attacks (≥2 per year), have one attack in the setting of chronic kidney disease (CKD) of stage 2 or worse, have tophaceous deposits found on examination or imaging, or have a history of urolithiasis. This patient developed an adverse reaction to allopurinol but still needs urate-lowing therapy. Febuxostat is a newer non-purine, non-competitive xanthine oxidase inhibitor, which is a viable alternative to allopurinol. It can be used in patients with mild to moderate CKD and is safe to try after an adverse reaction or failure of allopurinol.
Anti-inflammatory prophylaxis to prevent gout attacks is recommended when urate-lowering therapy is initiated because of the paradoxical increased risk of acute gout attacks when serum urate levels are rapidly decreased by medication. Prophylaxis should be continued in the presence of any active disease (tophi or flares). Colchicine is a first-line option for gout prophylaxis and should not be discontinued in this patient who requires flare prophylaxis during urate-lowering therapy.
Pegloticase is an intravenous synthetic uricase replacement approved for treatment-failure gout. Pegloticase is immunogenic, and the development of antibodies eventually occurs in most patients taking the drug, which leads to reduced effectiveness and increases the risk of hypersensitivity reactions.
The uricosuric drugs probenecid and sulfinpyrazone promote kidney clearance of uric acid by inhibiting urate-anion exchangers in the proximal tubule responsible for urate reabsorption. These agents are relatively contraindicated in patients with impaired kidney function or those at risk for kidney stones.
- In patients with gout who require urate-lowering therapy, febuxostat is a viable alternative for those who have an adverse reaction to allopurinol.
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