No Benefit to More Intensive Urate Lowering in Gout Save

While treat-to-target (T2T) is commonly advocated in gout management, it is unknown if T2T (or more intensive T2T) may result in less bony erosions in gout. Dalbeth et al has studied this is a prospective trial noted that more intensive serum urate lowering is difficult to achieve (orally), carries a high medication burden and does not improve bone erosion scores those with erosive gout.

A 2-year, double-blind randomized controlled trial of 104 erosive gout patients on oral urate–lowering therapy (ULT) orally and who had serum urate levels of ≥0.30 mmoles/liter (>5 mg/dl) at baseline. (editors note: uric acid 6 mg/dl = 0.357 mmol/L)

Participants were randomized to either an intensive serum urate target of <0.20 mmoles/liter (<3.4 mg/dl) or a standard target of <0.30 mmoles/liter. Oral ULT with either allopurinol, probenecid, febuxostat, and benzbromarone, was used and escalated to maximal doses per protocol. The primary end point was the total computed tomography (CT) bone erosion score. 

Despite the intensive group having significantly lower uric acid levels (P = 0.002), the intensive treatment group was less likely to achieve target uric acid level by year 2 (62% versus 83%; P < 0.05) compared to the standard T2G group.

The intensive target patients were more likely to receive higher doses of allopurinol (746 ± 210 mg/day versus 497 ± 186 mg/day; P < 0.001) and more combination therapy (P = 0.0004), compared to the standard target group.

CT bone erosion scores increased marginally in both treatment groups over 2 years, with no between-group difference (P = 0.20).

Moreover, there were no between group differences in  OMERACT core outcome clinical domains (gout flares, tophi, pain, patient's global assessment of disease activity, health-related quality of life, and activity limitation) over 2 years and adverse event rates were similar.

These findings suggest that the common, current standard serum urate target of <0.30 mmoles/liter is appropriate and that more intensive lowering of urate does not lead to better clinical, X-ray or safety outcomes in erosive gout patients.