Colchicine prophylaxis with allopurinol – is six months enough?

4 minute read

Gout patients who stopped colchicine began to have as many flares as those who hadn’t had the drug at all.

A New Zealand randomised controlled trial has found that in the first six months of a ‘start-low go-slow’ allopurinol strategy, placebo cannot match colchicine in preventing gout flares. 

But unexpectedly, in the following six months, patients who stopped colchicine caught up to have as many flares as those who’d not had colchicine at all. 

In one of the first trials to look at anti-inflammatory prophylaxis when starting urate lowering therapy, the researchers reported potential benefits to using colchicine prophylaxis in the first six months. 

“People who take colchicine for six months while on allopurinol have fewer flares than those receiving placebo,” co-author Professor Lisa Stamp of the University of Otago told The Medical Republic. 

“Therefore, prescribing colchicine in this setting can be beneficial,” said Professor Stamp, adding that it could be potentially longer if patients are still flaring at the end of the six months. 

The aim of the trial, which was published in the Annals of the Rheumatic Diseases, was to determine whether placebo was non-inferior to low-dose colchicine in reducing gout flares over the first six months of starting allopurinol, with a further six-month follow-up. 

While colchicine prophylaxis is recommended by the British Society of Rheumatology and the European Alliance of Associations for Rheumatology (EULAR), it was done so in context of an older allopurinol protocol, where full doses of allopurinol were used from the get-go when commencing urate lowering therapy. 

More recently, patients commencing allopurinol start on a low dose with a gradual dose escalation to achieve target serum urate – the so-called ‘start-low go-slow’ strategy.  

Data suggest gout flares are less of a risk when using this strategy, although previous clinical trials to investigate anti-inflammatory prophylaxis to prevent flares were of short duration and had no follow-up after stopping prophylaxis. 

The current study recruited 200 patients who’d had a gout flare in the previous six months, met recommendations for starting urate lowering therapy and had a serum urate of at least 0.36mmol/L. 

They were randomised 1:1 to receive either 0.5mg colchicine or placebo daily for six months in addition to a start-low go-slow allopurinol regimen: patients were started on either 50mg or 100mg allopurinol daily, depending on existing kidney function, and this was increased monthly until they achieved target serum urate.  

At the end of six months, there were more flares in the placebo group than the colchicine group, with an average 0.61 vs 0.35 flares respectively, which did not meet the prespecified non-inferiority margin. 

After the six months, and peaking at nine months, there was an increase in flares among the colchicine group that was not seen in the placebo group. 

“This is a very interesting finding for which we are unsure of the cause,” Professor Stamp said.  

“It is likely that these people will have monosodium urate crystals present so are at risk of flares, but this should also be the case for the placebo group.” 

This increase in flares for the colchicine group meant that there was no net difference in flares between the two groups over the entire 12-month period. 

The number of patients experiencing adverse events and the type of event were similar between groups. While small in number, there were more patients in the colchicine group experiencing serious adverse events (seven, versus two for placebo), including two deaths, though none were considered unrelated to the colchicine. 

“Despite the recommendations that anti-inflammatory prophylaxis should be used when commencing [urate lowering therapy], there are few trials specifically examining the risks and benefits of this approach,” wrote the authors. 

“These results will inform discussions between healthcare professionals and people with gout about the risks and benefits of colchicine prophylaxis when starting allopurinol.” 

It has been suggested that colchicine prophylaxis might make allopurinol escalation more tolerable for patients, but the data from this study were unable to support this.  

“The urate levels were the same in both groups over the 12 months suggesting that adherence to the allopurinol was equivalent,” Professor Stamp told The Medical Republic

“However, there are many factors that are important in adherence, and we can’t be sure that colchicine does not have an effect, particularly outside a clinical trial setting or longer term.” 

Annals of the Rheumatic Diseases 2023, online 31 August 

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