Urate-Lowering Therapy in Patients with Gout

Ritch te Kempe, PhD, Maastricht University, Maastricht, the Netherlands, and colleagues recently conducted a systematic review with meta-regression analysis to synthesize evidence of the effect of contextual factors on the efficacy of urate-lowering therapy on serum urate as an outcome in patients with gout. Results were reported in Seminars in Arthritis and Rheumatism [doi.org/10.1016/j.semarthrit.2022.152049].

The review included randomized controlled trials (RCTs) from updated Cochrane reviews. Eligible RCTs explored the role of any contextual factor on the efficacy of urate-lowering therapy on serum urate in gout patients. For contextual factors with sufficient data (defined as ≥3 trials), the researchers performed a mixed-effects meta-regression analysis with trial and comparison as random effects; specific contextual factors were modeled as fixed factors

The review included eight RCTs. The effect modification by contextual factors was examined for age, sex, race, renal function, cardiovascular comorbidity, tophi, thiazide-diuretic use, and previous use of urate-lowering therapy. Four trials included crude data stratified by renal function (36 randomized comparison) and were suitable for meta-analysis.

Pooled estimates indicated that gout patients with normal, mildly impaired, or moderately impaired renal function were consistently more likely to achieve target serum urate with urate-lowering therapy compared with controls.

Among RCTs that compared urate-lowering therapy with placebo (30 comparisons), there were no statistically significant differences in the effects of urate-lowering therapy on achieving target serum urate between those with normal renal function (odds ratio [OR], 66.87; 95% confidence interval [CI], 11.39-392.75), compared with mildly (OR, 28.54; 95% CI, 5.11-159.46) and moderately (OR, 21.45; 95% CI, 3.20-143.64) impaired renal function. The effects of urate-lowering therapy seemed lower among those with severely impaired renal function (OR, 9.13; 95% CI, 0.96-86.97).

Data on other contextual factors were insufficient to draw conclusion on effect modification.

In summary, the authors said, “Few RCTs report stratified analyses exploring the role of contextual factors. Urate-lowering therapy seemed effective in reaching the serum urate target in all levels of renal function, though severely impaired renal function appeared to render a slight disadvantage.”