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Urate-Lowering Therapy — ABIM Board MCQ

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HardUrate-Lowering TherapyABIM Board

A 57-year-old Korean American man is evaluated for an acutely painful, swollen right ankle that began yesterday. Synovial fluid contains needle-shaped, negatively birefringent crystals; Gram stain is negative. This is his third gout flare during the past 12 months. He has stage 3b chronic kidney disease, with an estimated glomerular filtration rate of 42 mL/min/1.73 m². Serum urate is 9.6 mg/dL. Testing obtained previously because of his ancestry shows that he carries HLA-B*58:01. He has no history of cardiovascular disease or nephrolithiasis. Liver aminotransferase levels are normal. Prednisone is started for the current flare. He has previously tolerated low-dose colchicine and takes no interacting medications. Which of the following is the most appropriate urate-lowering strategy?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: A — Initiate febuxostat 40 mg daily now with colchicine prophylaxis and titrate to a serum urate below 6 mg/dL

Explanation lettering: B = shown as A · D = shown as B · E = shown as C · A = shown as D · C = shown as E

Frequent gout flares (at least 2 annually) are a strong indication for urate-lowering therapy. Although allopurinol is ordinarily preferred, HLA-B*58:01 markedly increases the risk of allopurinol hypersensitivity syndrome and severe cutaneous adverse reactions; treatment with allopurinol is therefore not advisable in this carrier. Febuxostat is an appropriate alternative xanthine oxidase inhibitor, particularly because stage 3b chronic kidney disease makes a xanthine oxidase inhibitor preferable to probenecid. His absence of established cardiovascular disease removes an important concern associated with febuxostat use. Febuxostat should be started at no more than 40 mg daily and titrated using serial serum urate measurements to a target below 6 mg/dL. Urate-lowering therapy may be initiated during an actively treated flare rather than delayed, and anti-inflammatory prophylaxis should accompany initiation for at least 3–6 months. A is unsafe because low dosing does not eliminate HLA-associated allopurinol hypersensitivity risk. C uses an appropriate agent but unnecessarily delays indicated therapy. D is less appropriate because uricosuric therapy is less effective in moderate-to-severe chronic kidney disease, for which a xanthine oxidase inhibitor is preferred. E ignores his strong indication for therapy based on flare frequency; tophi or radiographic damage are not required.

Reference: 2020 American College of Rheumatology Guideline for the Management of Gout (2020) — https://pmc.ncbi.nlm.nih.gov/articles/PMC10563586/ Allopurinol Tablets Prescribing Information (April 2024) — https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/018832s056s058s061%2C018877s063s065s068lbl.pdf ULORIC (febuxostat) Prescribing Information (April 2023) — https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021856s015lbl.pdf