Is it reasonable to discontinue allopurinol (xanthine oxidase inhibitor) in a patient with a history of gout who has remained asymptomatic for years?

From the Guidelines

Discontinuing allopurinol after years without gout flares is generally not recommended, even with long periods of stability, as it may lead to a significant increase in the risk of gout flares returning, often more severely than before. Allopurinol works by lowering uric acid levels to prevent crystal formation in joints, and stopping it typically leads to uric acid rising back to pre-treatment levels within 1-2 weeks 1. If discontinuation is being considered, it should only be done under a physician's supervision with regular uric acid monitoring. The physician might recommend a gradual taper rather than abrupt cessation. Certain patients with resolved risk factors (significant weight loss, improved kidney function, or elimination of medications that raise uric acid) might be candidates for a trial off allopurinol, but this represents a minority of cases.

Some key points to consider when deciding whether to discontinue allopurinol include:

• The risk of gout flares returning after stopping allopurinol, which can be more severe than before 2
• The importance of regular uric acid monitoring if discontinuation is being considered 3
• The potential benefits of lifelong uric acid-lowering therapy in preventing painful flares and joint damage 4
• The need for shared decision-making with the patient to review possible harms and benefits of urate-lowering therapy 5

It's also important to note that evidence is insufficient to determine the effectiveness of discontinuing urate-lowering therapy after 5 years 4, and that patients with higher serum urate levels are at greater risk of gout flares 2. Therefore, it is generally recommended to continue allopurinol therapy indefinitely to prevent gout flares and joint damage, unless there are compelling reasons to discontinue it, such as resolved risk factors or significant adverse effects.

From the FDA Drug Label

Allopurinol tablets are indicated in: 1. the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy). Treatment with allopurinol tablets should be discontinued when the potential for overproduction of uric acid is no longer present.

The decision to discontinue allopurinol in a patient who has been on it for years without a gout flareup should be made on an individual basis. Key factors to consider include:

• The patient's uric acid levels and whether they are still elevated
• The presence of tophi or other signs of chronic gout
• The patient's renal function and overall health Since the patient has not had a gout flareup, it may be reasonable to consider discontinuing the medication, but this should be done under the guidance of a healthcare provider and with close monitoring for signs of gout recurrence or other adverse effects 6.

From the Research

Discontinuing Allopurinol in Gout Patients

• There is no direct evidence to suggest that discontinuing allopurinol is reasonable for patients who have not experienced a gout flareup in years 7, 8, 9, 10, 11.
• Studies have focused on the efficacy and safety of allopurinol, as well as patient adherence and persistence with the medication 7, 8, 10, 11.
• One study found that long-term persistence of xanthine oxidase inhibitors, including allopurinol, was suboptimal, and that poor health literacy was a common reason for discontinuation 7.
• Another study suggested that increasing the dose of allopurinol above the recommended dose can be effective and safe in patients with chronic gout, including those with renal impairment 8.
• A retrospective cohort study compared the safety and efficacy of febuxostat, allopurinol, and benzbromarone in Chinese gout patients, but did not address the issue of discontinuing allopurinol 10.
• A study on patient nonadherence to allopurinol found that patients often stop taking the medication because they want to lead a normal life or test if they really need it 11.

Considerations for Discontinuing Allopurinol

• Patients who have been on allopurinol for years without a gout flareup may still require ongoing treatment to prevent future flares 7, 8.
• The decision to discontinue allopurinol should be made on a case-by-case basis, taking into account individual patient factors and medical history 9, 10, 11.
• There is no clear evidence to support the idea that patients who have not experienced a gout flareup in years can safely discontinue allopurinol without increasing their risk of future flares 7, 8, 9, 10, 11.