How to address allopurinol ‘failure’ in gout: opinion


By Selina Wellbelove

25 Mar 2024

Rheumatologists have proposed a framework for assessing allopurinol failure in patients with gout that offers practical advice on how clinicians should respond to various ‘failure’ scenarios to boost the chances of treatment success.

Allopurinol ‘failure’ is considered common in clinical practice, but only a very small number of people are unable to reach target serum urate when taking regular allopurinol at a sufficient dose.

As such, the New Zealand researchers Professor Lisa Stamp and Professor Nicola Dalbeth said that healthcare professionals should fully explore and address the potential reasons for persistently low urate levels or lack of clinical improvement in gout patients before deeming it to have failed.

“Understanding the causes of allopurinol ‘failure’ underpins the approach required to turn ‘failure’ into ‘success’ in gout management,” they stressed in their paper published in The Journal of Rheumatology [link here]. 

In the first instance, if target serum urate levels are not achieved while on allopurinol treatment, clinicians should ask where the drug is being sourced to rule out counterfeit products.

However, two of the most common drivers of treatment failure are “under-dosing and lack of regular prescribing by healthcare professionals,” the authors noted.

A key issue was that 300mg daily, which is widely considered a standard dose of allopurinol, is ineffective in achieving target serum urate in most patients.

This was demonstrated by the FACT trial, in which allopurinol was administered at a fixed dose of 300mg even with eGFR>50mls/min/1.73m2; results showed that only one-fifth (21%) attained a serum urate of <0.36mmol/L.

The authors stressed that allopurinol dose escalation beyond 300mg to the maximum approved dose to achieve target serum urate is safe and effective, even in gout patients with renal impairment.

“It is recommended that allopurinol is commenced at low dose (e.g. 50-100mg daily depending on renal function) to minimise the risk of the rare but potentially life-threatening allopurinol hypersensitivity syndrome (AHS),” but this should then be “gradually increased in 50-100mg increments to achieve target serum urate.

“Multiple studies have shown that target serum urate can be achieved in the vast majority of people with gout with this approach,” they stressed.

“It is important to recognise that there is a wide dose range for allopurinol (50-900mg daily), with no one fixed dose allowing target serum urate to be achieved in the majority”.

Elsewhere, lack of treatment adherence is also a key factor in hindering allopurinol outcomes, with analysis showing that in areas where the drug was the most prescribed urate-lowering therapy, only around one-quarter (26%) of patients received regular, uninterrupted treatment.

“Practitioners need systems to ensure regular prescribing of allopurinol for people with gout and build understanding about gout as a chronic disease of MSU crystal deposition that can be treated with long-term urate-lowering therapy,” the authors stressed.

They also noted that some gout patients might require higher doses of allopurinol due to genetic mutations or the use of concomitant medicines such as frusemide.

Clinicians should review gout diagnoses when allopurinol does not improve urate levels as expected. If the diagnosis is confirmed, then intensification of gout flare prophylaxis and treatment, without modifying allopurinol treatment, should be considered. Alternatively, they noted that serum urate may need to be further reduced for faster dissolution of MSU crystals.

“It is important to recognise that many of the common reasons that allopurinol ‘fails’ will also apply to alternative urate-lowering therapies. Before labelling allopurinol as having “failed”, healthcare providers must explore and address potential reasons and base subsequent treatment decisions on the reasons identified,” the authors concluded.

Already a member?

Login to keep reading.

Email me a login link