Recent flares, starting dose predict gout flare risk in first 6 months of allopurinol
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Key takeaways:
- In the first 6 months of allopurinol therapy, gout flare risk was significantly linked to flare in the month prior and a 100 mg starting dose.
- Some patients may require longer prophylaxis duration.
When initiating allopurinol for gout under a “start low, go slow” dosing strategy, flares in the first 6 months are most common in patients starting with 100 mg daily, or who flared in the month before beginning therapy, according to data.
“While sustained reduction of serum urate below 0.36 mmol/L over some months is associated with a reduction and cessation of gout flares, there is a paradoxical increase in gout flares during the early stages after commencing urate-lowering therapy,” Lisa K. Stamp, FRACP, PhD, of the University of Otago, in New Zealand, and colleagues wrote in Arthritis Care & Research.
“The ability to predict which people with gout are at increased risk of gout flares when commencing urate-lowering therapy and/or those who might flare when the anti-inflammatory prophylaxis is discontinued, and therefore would benefit most from anti-inflammatory prophylaxis, is of clinical significance,” they added.
To examine potential predictors of gout flare when initiating allopurinol, Stamp and colleagues conducted a post-hoc analysis of a previous study, in which they tested colchicine vs. placebo for flare prevention in the first 6 months of a “start low, go slow” allopurinol regimen. The researchers used multivariate logistic regression models to identify factors that independently predicted gout flares in the first and last 6 months of the trial.
The “start low, go slow” strategy consisted of an initial daily dose of either 50 mg or 100 mg allopurinol, depending on estimated glomerular filtration rate, which then increased monthly by 50 mg or 100 mg until serum urate was below 0.36 mmol/L at three consecutive visits.
For the first 6 months after starting allopurinol, the analysis revealed significant associations between gout flare risk and the presence of a flare in the month prior (OR = 2.65; 95% CI, 1.36-5.17), as well as a starting dose of 100 mg (OR = 3.21; 95% CI, 1.41-7.27), according to the researchers. In the last 6 months of the trial, after colchicine or placebo had been stopped, the predictors for gout flare were:
- having received colchicine (OR = 2.95; 95% CI, 1.48-5.86);
- at least one flare in the month prior to stopping colchicine or placebo (OR = 5.39; 95% CI, 2.21-13.15); and
- serum urate of 0.36 mmol/L or greater at month 6 (OR = 2.85; 95% CI, 1.14-7.12).
“These data suggest that for people with ongoing gout flares during the first six months of starting allopurinol who have not yet achieved serum urate target, a longer period of prophylaxis may be required,” Stamp and colleagues wrote.
“Although anti-inflammatory prophylaxis when starting urate lowering therapy is recommended in order to prevent gout flares by most [of] the major gout guidelines, there are limited data on the effect on gout flares, particularly in the period after stopping anti-inflammatory prophylaxis, on which to base the guidelines,” they added. “Furthermore, many people with gout have comorbidities and other concomitant medications and do not wish to add additional medications.”
Perspective
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Carlos M. Alonso, MD, FACR, RhMSUS
Managing gout appears straightforward in theory but proves complex in real-life scenarios. Factors such as treatment adherence, alcohol intake, dietary habits, and concurrent health conditions contribute to this challenge.
One of the most prevalent misconceptions among patients and primary care providers is the use of uric acid-lowering drugs during acute attacks and discontinuing them afterward. Additionally, there is a significant challenge in preventing gout attacks while aiming to lower serum uric acid levels. This analysis looked for factors that predict gout flares during the first 6 months of starting allopurinol therapy and the subsequent 6 months.
Insights from the presented data highlight several important treatment considerations. Initiating allopurinol at a low dose and gradually increasing it, known as the “start low, go slow” approach, is advisable. For patients who recently experienced a flare or have not yet achieved their target uric acid levels, extending prophylactic treatment beyond 6 months should be considered.
There remain several unanswered questions regarding the best way to avoid gout flares after initiating uric lowering therapy, including the exploration of alternative prophylactic options, such as low-dose NSAIDs, low dose glucocorticoids, or interleukin-1 therapy. Nonetheless, this study provides valuable insights. As always, treatment must be individualized to the patient's specific circumstances.
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