Treatment failure gout: failure to treat?

Treatment options for gout are well established and reasonably effective. They include anti-inflammatory agents such as non-steroidal anti-inflammatory drugs (NSAIDS), glucocorticoids and colchicine and urate-lowering therapies such as allopurinol and probenecid. However, despite the availability of effective urate-lowering therapy, there remains a subset of patients with gout who, despite aggressive therapy, have intractable disease, manifest as recurrent gout flares, chronic arthritis and progressive tophaceous deposits. These patients are referred to as having “refractory gout” or “treatment failure gout” (TFG). The term “treatment failure gout” includes five ways by which patients may develop poorly controlled disease. These pertain mainly to the use of urate-lowering therapy and include delayed prescribing, inadequate dosage, intolerance, noncompliance and inadequate response in spite of generally acceptable dosages. (Table 1) The new xanthine oxidase inhibitor febuxostat (Uloric) has not been studied in TFG, but may ultimately prove useful for this indication. Febuxostat is discussed elsewhere in this journal. Regardless of the pathway, all patients with treatment failure gout are unable to reduce and maintain serum urate below the therapeutic target of 6 mg/dl. 2 An estimated 100,000 to 300,000 of the nearly 3 million cases of gout in the US are not adequately managed with current therapies.3 Additionally, many patients with gout have significant and multiple co-morbidities that preclude the use of those therapies. Allopurinol, the most common treatment used to lower serum urate levels, is generally regarded as safe and effective.3 It lowers serum urate by inhibiting the purine nucleotide pathway enzyme xanthine oxidase. However, about 20% of patients receiving allopurinol report side effects and about 5% discontinue the medication due to intolerance.4 Allopurinol may also be contraindicated because of potential adverse drug interaction with azathioprine.5 Moreover, the presence of kidney disease may preclude adequate dosing because allopurinol-related toxicity is increased in the presence of significant renal impairment. Even though severe toxicity is rare, inadequate dosing of allopurinol to achieve target serum urate level <6.0 mg/dl is common. Noncompliance is another common problem with allopurinol: in one study patients in a managed care cohort were non-compliant with allopurinol about 44% of the time.