From the Guidelines
Febuxostat should not be used to manage asymptomatic or secondary hyperuricemia due to the lack of clinical benefit and potential risks associated with its use. The most recent and highest quality study, the 2020 American College of Rheumatology guideline for the management of gout 1, recommends against initiating pharmacologic urate-lowering therapy (ULT) in patients with asymptomatic hyperuricemia. This recommendation is based on high certainty of evidence, which suggests that treating asymptomatic hyperuricemia with ULT, including febuxostat, does not provide clinical benefit and may expose patients to unnecessary risks.
The risks associated with febuxostat therapy, including cardiovascular events, liver function abnormalities, and serious skin reactions, outweigh any potential benefits in asymptomatic patients. Additionally, febuxostat carries a boxed warning regarding increased risk of cardiovascular death compared to allopurinol in patients with established cardiovascular disease. Current clinical guidelines, such as those from the 2020 American College of Rheumatology 1 and the 2014 multinational evidence-based recommendations for the diagnosis and management of gout 1, recommend addressing the underlying causes of secondary hyperuricemia rather than treating the elevated uric acid level itself when patients are asymptomatic.
Some key points to consider when managing hyperuricemia include:
- The 2020 American College of Rheumatology guideline recommends against initiating ULT in patients with asymptomatic hyperuricemia, with a high certainty of evidence 1.
- The 2014 multinational evidence-based recommendations for the diagnosis and management of gout also recommend against pharmacological treatment of asymptomatic hyperuricaemia, with a moderate level of evidence and a grade of recommendation of D 1.
- A systematic review in support of an American College of Physicians clinical practice guideline found that use of urate-lowering therapy with allopurinol or febuxostat decreases serum urate levels, but the evidence for its use in asymptomatic patients is limited 1.
In summary, febuxostat should not be used to manage asymptomatic or secondary hyperuricemia, and treatment should be reserved for patients with clinical manifestations of gout or specific conditions where uric acid reduction has demonstrated benefit, as recommended by the most recent and highest quality studies 1.
From the Research
Reasons to Avoid Febuxostat for Asymptomatic or Secondary Hyperuricemia
- Febuxostat is not typically recommended for asymptomatic or secondary hyperuricemia due to the potential risks associated with its use, as seen in studies such as 2 and 3.
- The use of febuxostat in patients with asymptomatic hyperuricemia without gout may not be justified, as the benefits of treatment may not outweigh the risks, as suggested by 4.
- Allopurinol is often considered the first-line treatment for hyperuricemia and gout, and febuxostat may be reserved for patients who are intolerant to allopurinol or have contraindications to its use, as mentioned in 5.
- The cardiovascular safety of febuxostat compared to allopurinol is still a topic of debate, with some studies suggesting that febuxostat may be associated with a higher risk of cardiovascular events, as seen in 3.
- The treatment of asymptomatic or secondary hyperuricemia with febuxostat may not be cost-effective, especially considering the potential risks and the availability of alternative treatments, as discussed in 5 and 6.
Key Considerations
- The decision to use febuxostat for asymptomatic or secondary hyperuricemia should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history, as suggested by 2 and 4.
- Patients with a history of cardiovascular disease may be at higher risk for adverse events when treated with febuxostat, as seen in 4 and 3.
- The monitoring of serum uric acid levels and cardiovascular risk factors is crucial when using febuxostat to treat hyperuricemia, as mentioned in 5 and 6.