What are the indications for chronic treatment of symptomatic gout and how should this be managed?
Lifelong ULT is indicated for gout patients characterized by:
- • Frequent flares, often defined as more than two to three flares over a 1-year period.
- • Renal stones (urate or calcium).
- • Tophaceous gout (detected on examination or radiographically).
- • Moderate-to-severe CKD.
Indications for xanthine oxidase inhibition versus uricosuric therapy, along with dosing information and side-effect profiles, (Hypouricemic Agents and Colchicine). Xanthine oxidase inhibition with allopurinol is considered to be first-line ULT. The starting dose of allopurinol is 100 mg/day (with even lower initial doses with marked renal impairment) followed by gradual upward titration (often >300 mg/day) to achieve a serum urate goal of <6 mg/dL, or <5 mg/dL in patients with tophi. This “start low and go slow” strategy can be used effectively in the vast majority of patients and even in patients with renal impairment, provided regular monitoring is in place. HLA-B∗5801 screening prior to the initiation of allopurinol should be considered for patients at increased risk for severe hypersensitivity (e.g., Koreans and possibly African Americans with stage 3 or worse CKD; patients of Han Chinese or Thai descent), which carries a mortality risk approaching 20%. Febuxostat (typically second line therapy for those failing allopurinol) is typically initiated at a daily dose of 40 mg (approximately equivalent to allopurinol 300 mg) and titrated upwards after 2 to 3 weeks to 80 mg/day if the serum urate goal has not been achieved. Febuxostat appears to be well tolerated in patients with moderate CKD. Probenecid is contraindicated in patients who overproduce uric acid (see Question 6) or have a history of nephrolithiasis, and lacks efficacy in those with impaired renal function (glomerular filtration rate [GFR] <50 mL/minute). Pegloticase (a recombinant pegylated uricase dosed intravenously at 2-week intervals) is approved for advanced gout that has proven refractory to other therapies (see Chapter 86 : Hypouricemic Agents and Colchicine). Drug-related antigenicity has limited the long-term use of this agent.
