Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial
RCT (n=200) found placebo was not non-inferior to colchicine in prevention of gout flares during the first 6 months of ‘start-low go-slow’ allopurinol treatment (0.61 vs 0.35 flares/month, respectively; mean difference 0.25 [0.07 to 0.44], non-inferiority p=0.92).
Source:
Annals of Rheumatic Diseases
SPS commentary:
It is recommended that people with gout receive anti-inflammatory prophylaxis for 3–6 months when commencing urate lowering therapy, to prevent gout flares. Colchicine is widely used and is specifically recommended as the first-line agent for prophylaxis by the British Society for Rheumatology.
The researchers note that until recently, full doses of allopurinol (300mg daily) were immediately started in clinical trials. However, it is now recommended that allopurinol is commenced at low doses (50–100 mg daily) and gradually up-titrated to achieve target serum urate levels (‘start-low go-slow’ strategy), primarily due to the risk of the rare but potentially fatal allopurinol hypersensitivity syndrome. The use of this more gradual dose escalation strategy may be associated with lower risk of flares.
This study failed to show the non-inferiority of placebo to colchicine during the initial 6 months of allopurinol treatment. However, when the colchicine/placebo was discontinued at the end of month 6, there was a rise in the number of gout flares in those previously receiving colchicine which was not observed in those previously receiving placebo. This meant that over the entire 12 month period, there was no difference between the groups in the mean number of gout flares per month. Based on this finding, the authors suggest that continuation of anti-inflammatory prophylaxis beyond 6 months may be of benefit for some individuals.