medwireNews: Serum urate concentration is a valid surrogate endpoint for the reduction or absence of gout flares, suggest study findings presented at the ACR Convergence 2021 virtual meeting and published in The Lancet Rheumatology.
Lisa Stamp (University of Otago, Christchurch, New Zealand) and co-authors say that their analysis of patient-level data from two randomized controlled trials (RCTs) on urate-lowering therapies in people with gout “support[s] a treat-to-target serum urate approach in the management of gout.”
Using the UK- and New Zealand-based studies, Stamp and team identified 343 serum urate responders and 245 nonresponders, when response was defined as a mean serum urate level below 6.0 mg/dL during the first 12 months of gout treatment, typically with allopurinol.
They found that risk for a gout flare between months 12 and 24 was a significant 71% lower among the serum urate responders than among the nonresponders, after adjustment for flare history, baseline serum urate, baseline tophi, and randomization group (nurse- vs general practitioner-led care) in the UK study. The flare rates were 26.5% and 63.7% for serum urate responders and nonresponders, respectively.
The fact that the association was independent of the original randomized treatment allocation suggests “that the reduction in serum urate is primarily responsible for the absence of flares,” Stamp et al remark.
The mean number of monthly flares per participant between 12 and 24 months was also significantly lower in serum urate responders than in nonresponders, at 0.69 vs 2.09, with an adjusted mean difference of 0.41 between the two groups.
Exploratory analyses with response cutoffs reduced to 5.0 mg/dL or increased to 7.0 mg/dL yielded similar outcomes, suggesting that “[f]urther research is required to identify the optimal target serum urate threshold (ie, with explicit use of diagnostic accuracy tests),” say the investigators.
They also note that serum urate response was associated with tophus regression. Specifically, 71.7% of 53 responders with tophus at baseline lost the sentinel tophus during follow-up compared with 38.1% of 21 nonresponders with a baseline tophus, a significant difference.
There were no significant differences between the two groups, however, in tender and swollen joint counts, health-related quality of life, and radiologic outcomes.
Stamp and colleagues say that the “[u]se of serum urate as a treatment target and outcome measure has become controversial in view of the 2017 American College of Physicians [ACP] guidelines, which advocated a treat-to-symptom rather than a treat-to-target serum urate approach to gout management."
Nonetheless, they conclude: “We have shown in this study that serum urate is a valid surrogate for gout flares and tophi and we hope that the highest level of evidence based on RCTs, such as that presented here, will enable recommendations to be aligned between rheumatology organisations and the ACP.”
In an accompanying comment, Thomas Bardin and Pascal Richette, both from The University of Paris in France, say that the study “brings reassurance on the validity” of using serum urate concentration as a surrogate endpoint in gout trials and provides “an important piece of evidence in favour of the treat-to-target approach.”
They add: “It remains to be seen if this evidence, which is limited by the fact that it relies on a post-hoc analysis, will be enough to convince the ACP.”
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ACR Convergence 2021; 3–9 November
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00319-2
Lancet Rheumatol 2021; doi:10.1016/S2665-9913(21)00358-1