Pegloticase Treatment Significantly Decreases Blood Pressure in Patients With Chronic Gout

Serum urate is correlated with blood pressure (BP), and lowering urate may decrease BP, but a consistent effect has not been observed. Here, we evaluated whether pegloticase, a recombinant uricase conjugated to polyethylene glycol, which can lead to persistently low serum urate levels (<1 mg/dL), can modulate BP in subjects with chronic refractory gout. This post hoc analysis used results from two 6-month randomized clinical trials in which subjects were treated with 8 mg pegloticase every 2 or 4 weeks (q2w or q4w) or placebo. Responders in this study were defined as those individuals in whom a persistently low urate level (<6 mg/dL and usually <1 mg/dL) was maintained. Serial sitting BP was measured in 173 subjects, and estimated glomerular filtration rate was determined at baseline and after 3 and 6 months. Significant reductions in mean arterial pressure (MAP) from baseline to 6 months were noted in q2w responders ( P =0.0028), whereas reductions in MAP in other groups were not significant. Significant decreases in both systolic and diastolic BP paralleled the change in MAP. Of the 62% of q2w responders exhibiting persistent decreases in MAP, there were no significant differences in baseline age, sex, race, weight, body mass index, history of hypertension, hyperlipidemia, history of coronary artery disease, gout duration, MAP, serum urate, estimated glomerular filtration rate or urinary uric acid/creatinine ratio compared with those who did not lower MAP. No significant changes in estimated glomerular filtration rate occurred in any of the groups during the study. Responders to biweekly pegloticase who maintained a persistently lower serum urate level throughout the trial experienced significant reductions in both systolic and diastolic BP that were independent of changes in renal function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00325195.