Placebo not non-inferior to colchicine in preventing gout flares in the first 6 months of starting allopurinol using ’start-low go-slow’ strategy.
Introduction
Gout is a very common condition, affecting up to 4% of adults in developed countries. The symptoms tend to flare every so often, developing over a few hours and causing severe pain in the joints. It is caused by deposits of crystals of a substance called uric acid (urate) in the joints, which leads to inflammation.
Medical care aims to treat gout flares and reduce the immediate pain and inflammation caused
by the inflammatory response to the crystals. But there are also long-term treatments that can be used to bring down a person’s urate levels. One of these urate-lowering medicines is called allopurinol. Unfortunately, starting a urate-lowering therapy can itself cause a gout flare. To avoid this, an anti-inflammatory drug is recommended for 3–6 months when first starting allopurinol to help prevent flares. This is sometimes colchicine or a type of non-steroidal anti-inflammatory drug (NSAID). This sort of preventative treatment is called prophylaxis. But some doctors think that gradually increasing the allopurinol dose instead could avoid the need for an additional medicine to prevent possible flares. This allopurinol dose-escalation approach is called “start low go slow”.
What did the authors hope to find?
The authors wanted to find out whether anti-inflammatory treatment with colchicine is required when using the “start low go slow” allopurinol dosing strategy.
Who was studied?
The study included 200 people with gout. Everyone had experienced at least one gout flare in the past 6 months, and met the criteria for starting treatment with allopurinol.
How was the study conducted?
This was a non-inferiority, double-blind, randomised controlled trial. Everybody was started on allopurinol, with their dose increased every month until they had a reduction of their blood urate to a specific level. At the same time as starting allopurinol, everybody taking part was assigned by chance to one of two treatment groups to also receive either colchicine (the active medicine) or a placebo (a dummy that has no active medicine in it). Using chance in this way means that the groups will be similar and will allow the treatments to be compared objectively. During the treatment neither patients nor their doctors knew which group they were in.
The non-inferiority part means the researchers intended to show that the placebo was not worse than the colchicine. The study was not designed to see if the placebo was better than the colchicine.
The authors then looked to see how many gout flares people had per month in each group. The statistical plan meant that placebo would be declared non-inferior if it fell within a margin of 0.12 gout flares per month.
What were the main findings of the study?
The main finding was that placebo did not meet the specified margin. People taking placebo and allopurinol had significantly more gout flares per month than those receiving colchicine and allopurinol during the first 6 months of the study, mostly between the study start and Month 3. This means placebo was not non-inferior to low-dose colchicine in preventing gout flares during 6 months of anti-inflammatory prophylaxis when starting allopurinol.
Another important finding was that after stopping colchicine, gout flares rose – with no difference in the mean number of gout flares per month over the entire 12-month period.
Finally, there were numerically more serious adverse events with colchicine than placebo, although these side effects were not thought to be related to colchicine.
Are these findings new?
Yes, these are new findings.
What are the limitations of this study?
One limitation was that the study design did not allow quantification of flare severity. Another is that the study protocol said that people with stage 4 or 5 chronic kidney disease could not take part. This means the findings – particularly those around safety – may not apply to people with chronic kidney disease. This could be important, since people with chronic kidney disease are more likely to have gout than those without.
What do the authors plan on doing with this information?
These results will be translated into clinical care and will inform discussions between healthcare professionals and people with gout. They will help make decisions about the risks and benefits of colchicine prophylaxis when starting allopurinol. No further studies are planned.
What does this mean for me?
If you have gout, this information may help you to decide if you want to try colchicine.
If you have any concerns about your disease or its treatment, you should talk to your doctor or a healthcare professional involved in your care.
Date prepared: June 2024
Summary based on research article published on: August 2023
From: Stamp L, et al. Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial. Ann Rheum Dis 2023;82:1626–34. doi:10.1136/ard-2023-224731
Copyright © 2024 BMJ Publishing Group Ltd & European League Against Rheumatism. Medical professionals may print copies for their and their patients and students non commercial use. Other individuals may print a single copy for their personal, non commercial use. For other uses please contact our Rights and Licensing Team.
