CONTROLLING HYPERURICEMIA IN GOUT: MODERN PRINCIPLES OF URATE-LOWERING THERAPY
Keywords:
Gout, hyperuricemia, urate-lowering therapy, allopurinol, febuxostat, treat-to-target, tophi, monosodium urate.Abstract
Background: Gout is the most common inflammatory arthritis, caused by monosodium urate (MSU) crystal deposition that develops once serum urate persistently exceeds its physiological solubility threshold (approximately 6.8 mg/dL, or 404 µmol/L). Left inadequately treated, recurrent flares progress to chronic tophaceous gout with structural joint damage and disability.
Methods: This narrative review synthesizes current evidence on hyperuricemia control and urate-lowering therapy (ULT) in gout, drawing on the 2020 American College of Rheumatology (ACR) gout guideline, the 2016 EULAR evidence-based recommendations, and the pivotal CARES cardiovascular safety trial.
Results: A treat-to-target strategy — lowering and sustaining serum urate below an explicit threshold (<6 mg/dL generally; <5 mg/dL in patients with tophi or frequent flares) — allows gradual dissolution of existing crystal deposits and prevents new flares, with the rate of tophus resolution directly related to how far below the supersaturation threshold serum urate is maintained. Allopurinol, titrated gradually from a low starting dose to the target urate level, remains first-line therapy for essentially all patients; febuxostat is an effective alternative but carries a cardiovascular mortality signal versus allopurinol; uricosurics and pegloticase serve as add-on or last-line options. Anti-inflammatory flare prophylaxis for at least 3–6 months is essential during ULT initiation, since urate lowering itself can transiently mobilize crystals and precipitate flares.
Conclusion: Sustained, treat-to-target urate-lowering therapy combined with adequate flare prophylaxis is central to preventing structural joint damage and improving quality of life in gout, including in resource-constrained healthcare settings such as Uzbekistan, where low-cost allopurinol-based therapy and routine serum urate monitoring offer a feasible, high-yield strategy.
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