From the Guidelines
When allopurinol is not effective for gout treatment, febuxostat is typically the next medication to try, usually starting at 40mg daily and potentially increasing to 80mg daily if needed, as recommended by the 2017 updated EULAR evidence-based recommendations for the management of gout 1.
Treatment Options
- Febuxostat is a more potent xanthine oxidase inhibitor than allopurinol, and has been shown to be effective in lowering serum uric acid levels in patients with gout 1.
- Other options include probenecid, which works by increasing uric acid excretion through the kidneys, or lesinurad (Zurampic), which is used in combination with a xanthine oxidase inhibitor.
- For patients with severe tophaceous gout who don't respond to conventional therapy, pegloticase (Krystexxa), given as an intravenous infusion every two weeks, can rapidly reduce uric acid levels.
Preventing Gout Flares
- During any medication transition, colchicine (0.6mg once or twice daily), NSAIDs, or corticosteroids should be used to prevent gout flares, as recommended by the American College of Physicians 1.
- It's also essential to address underlying factors by limiting purine-rich foods, reducing alcohol intake (especially beer), maintaining adequate hydration, and managing comorbidities like obesity, diabetes, and hypertension.
Lifestyle Modifications
- The 2017 updated EULAR evidence-based recommendations for the management of gout also emphasize the importance of lifestyle modifications, including weight loss, avoidance of alcohol and sugar-sweetened drinks, and regular exercise 1.
- A diet rich in low-fat dairy products, fruits, and vegetables, and low in purine-rich foods, can help reduce serum uric acid levels and prevent gout flares.
From the Research
Treatment Options for Gout When Allopurinol is Not Effective
- Febuxostat is a potential alternative to allopurinol for patients with hyperuricemia and gout, as it has been shown to be more effective in lowering serum urate concentrations 2, 3, 4.
- In patients who cannot tolerate allopurinol, other treatment options include dietary changes, discontinuation of diuretic agents, and use of losartan or fenofibrate to treat concomitant hypertension or dyslipidemia 5.
- Uricosuric agents, such as probenecid, may be helpful in patients with normal or diminished urate excretion 5.
- Rasburicase, an Aspergillus urate oxidase, may be used to prevent acute hyperuricemia induced by chemotherapy for hematological malignancies, but its use is limited by the need for parenteral administration and lack of validated treatment schedules 5.
- Febuxostat has been shown to be effective in patients with allopurinol-resistant tophaceous gout, with rapid and sustained reduction in uric acid levels to target range 6.
Efficacy of Febuxostat Compared to Allopurinol
- Febuxostat has been shown to be more effective than allopurinol in lowering serum urate concentrations, with 53-62% of patients achieving a serum urate concentration of less than 6.0 mg per deciliter compared to 21% of patients receiving allopurinol 2.
- A systematic review and meta-analysis found that 70.7% of patients reached the target of serum urate with febuxostat therapy, compared to 44.4% with allopurinol 3.
- Febuxostat has also been shown to be effective in patients with renal dysfunction, with an advantage over allopurinol in terms of efficacy and safety 3, 4.
Safety and Tolerability of Febuxostat
- Febuxostat has been shown to be generally well tolerated, with adverse events mostly limited to liver enzyme elevations, nausea, arthralgias, and rash 4.
- Febuxostat does not require dosage adjustment in patients with mild to moderate renal impairment, making it a suitable option for patients with renal dysfunction 4.
- The safety profile of febuxostat has been shown to be favorable compared to allopurinol, with a lower risk of adverse events 3.