Anti-gout preparations
| Type | Recommendation |
|---|---|
| When to deprescribe | |
| CBR |
We suggest deprescribing be offered to older people taking long-term urate-lowering therapy who have been in clinical remission for at least a year, with a normal serum uric acid concentration (< 0.36 mmol/L for non-tophaceous gout, or < 6 mg/dL), no tophi, no flares, when the risks of adverse drug events, drug-drug interactions, and treatment burden outweigh the benefits of preventing gout reoccurrence. |
| CBR |
We suggest deprescribing be offered to older people taking long-term colchicine for prophylaxis of gout flares, except when initiating urate-lowering treatment for a short period of time (typically six months or more until no further attacks and the target serum uric acid concentration has been achieved). |
| Ongoing treatment | |
| CBR | We suggest continuing long-term urate-lowering therapy with tophi. |
| CBR | We suggest continuing long-term anti-gout preparations for evidence-based indications other than gout (e.g. colchicine used for pericarditis) for the appropriate duration of use, as the benefits of continued use likely outweigh the risks, under specialist care. |
| How to deprescribe | |
| CBR |
In general, we suggest halving the daily dose every two weeks, ensuring individuals remain symptom-free before initiating each tapering. Once half the lowest standard dose formulation is reached, we suggest ceasing completely. |
| Monitoring | |
| CBR |
We suggest closely monitoring for serum uric acid concentrations, renal function, and gout flares every two weeks for at least a month following deprescribing if practical. After this initial period, we suggest monthly monitoring for at least three months, followed by monitoring every six months thereafter. However, this should be tailored based on individual factors such as their preferences, responses and tolerance to deprescribing. If in-person visits are impractical, we suggest advising people to report symptom recurrence as needed. We suggest providing education on how to manage an acute gout attack. |
| CBR |
We suggest the periodic assessment of cardiovascular risks and the appropriate management of comorbidities in people with gout and/or hyperuricaemia, including offering lifestyle modification advice where appropriate to modify cardiovascular risk factors. |
CBR, consensus-based recommendation
Gout
Gout is the most prevalent form of inflammatory arthritis, caused by the accumulation of monosodium urate crystals in the joints, triggering an intensely painful immune response [494]. It is typically an acute, self-limiting condition that primarily affects the lower limb joints [495]. While hyperuricaemia is the strongest risk factor for gout, other factors such as age and sex also play a role, with gout being more common in men and increasing in prevalence with age [496]. Dietary intake of purine-rich foods, including meat, seafood, alcohol, and fructose-sweetened beverages, can contribute to hyperuricaemia [495]. However, a recent cohort study of adults without kidney disease or gout who were not taking urate-lowering or diuretic medications found that dietary factors had a minimal impact on serum uric acid concentrations compared to genetic factors [497]. Similarly, a previous Mendelian randomisation study found no causal relationship between increased alcohol consumption and the development of hyperuricaemia or gout [498]. Despite this, gout is frequently associated with comorbidities such as hypertension, diabetes, dyslipidaemia, chronic kidney disease, and obesity, which may benefit from lifestyle modifications. However, implementing these changes can be challenging for older people due to factors such as reduced appetite, altered food preferences, declining physical function, difficulty preparing meals, and financial constraints [499].
Serum uric acid
Elevated serum uric acid concentrations have been linked to chronic kidney disease and cardiovascular conditions, including hypertension, atrial fibrillation, heart failure, coronary artery disease, and cardiovascular mortality [500]. A recent cohort study found that men with gout who were not regularly dispensed allopurinol with serum uric acid concentration above the treatment target of 0.36 mmol/L had a significantly increased risk of cardiovascular disease [501]. However, the causal relationship between serum uric acid concentration and cardiovascular disease remains uncertain [500], and there is no clear evidence that lowering serum uric acid reduces major adverse cardiovascular events, all-cause mortality, or kidney failure [502].
Utilisation of urate-lowering therapy and colchicine
Long-term urate-lowering therapy (ULT) is recommended for all individuals with a confirmed diagnosis of gout, alongside the management of comorbidities [494]. Allopurinol is considered the first-line ULT, but febuxostat (a xanthine oxidase inhibitor) or probenecid may be prescribed if allopurinol is contraindicated or poorly tolerated [494]. Colchicine is commonly used to treat acute gout attacks and as prophylaxis to prevent flares when initiating or adjusting ULT [494]. When used prophylactically, colchicine should be continued until gout flares cease and target serum uric acid concentrations are achieved, which may take six months or longer [494].
We were unable to identify any direct evidence related to the deprescribing of anti-gout preparations in older people from the systematic review and meta-analysis. Recommendations are provided in this section following a Delphi consensus process.
The 2020 American College of Rheumatology (ACR) guideline conditionally recommends continuing ULT indefinitely if it is well-tolerated and not burdensome, based on very low-certainty evidence that most individuals in long-term clinical remission with controlled serum uric acid concentration experienced gout flares within five years of ULT discontinuation [503]. In many cases, the benefits of lifelong ULT in maintaining target serum uric acid concentration generally outweigh the risks of recurrent gout, which can impair quality of life and physical function as well as lead to long-term joint damage. Evidence specifically addressing ULT discontinuation in older people is lacking. A systematic review of younger adults (aged 42-60 years) found that gout recurrence following ULT discontinuation was high, ranging from 36% to 81%, with a recurrence timeframe of approximately one to 4.5 years.
Deprescribing decisions should be guided by a thorough assessment of factors such as changes in risk factors and concurrent medications that influence serum uric acid concentration (e.g. diuretics) [504]. In certain situations, ULT dose reduction or discontinuation may be appropriate, particularly for individuals at low risk of gout recurrence. If deprescribing is considered appropriate, evidence suggests that lower serum uric acid concentrations before and after deprescribing are associated with a reduced risk of recurrence [503, 505]. Maintaining a normal serum uric acid concentration (below 0.36 mmol/L in non-tophaceous gout or < 6 mg/dL) and remaining free of tophi or flares likely contributes to a lower risk of gout recurrence. For those who have achieved clinical remission for at least a year, or who have improved modifiable risk factors for hyperuricaemia (e.g. diet, change in concurrent medicines) and maintained a normal serum uric acid concentration, deprescribing may be considered when the potential harms of continued therapy, such as adverse drug events, drug-drug interactions, or treatment burden, outweigh the benefits of ongoing prevention of gout recurrence.
For people using anti-gout preparations for other long-term indications, continuation or discontinuation considerations may include an assessment of indications, duration of use, benefit-risk profile, goals of care as well as individual values and preferences.
The tapering approach and monitoring are based on pharmacological rationale and clinical experience, considering the possible gout recurrence associated with sudden changes in extracellular uric acid concentration [506]. Additionally, gout is associated with an increased risk of cardiovascular mortality [507]. Therefore, periodic assessment of cardiovascular risks is important, along with the appropriate management of comorbidities in people with gout and/or hyperuricaemia. Lifestyle modification advice should be offered to individuals where appropriate to modify cardiovascular risk factors.