Pegloticase Treatment Significantly Decreases Blood Pressure
in Patients With Chronic Gout/培戈洛酶显著降低慢性痛风患者的血压
Introduction
Gout results from chronically elevated serum urate. → Epidemiological studies have demonstrated relationships between hyperuricemia, gout, and hypertension. → The randomized control trial data available at present are insufficient to know whether UA-lowering therapy also lowers BP. → Key questions are whether more profound lowering of serum urate might have an effect on BP and whether lowering of serum urate without inhibition of xanthine oxidase might also have BP-lowering effects. → Pegloticase profoundly degrades urate and does not inhibit xanthine oxidase. → From the RCTs for pegloticase, we assess the impact of persistent, very low serum urate levels on BP in subjects with chronic refractory gout.
They were ≥18 years of age with chronic refractory gout, defined as baseline serum urate ≥0.476 mmol/L (8.0 mg/dL) and ≥1 of the following: (1) ≥3 self-reported gout flares during the previous 18 months; (2) ≥1 tophi; or (3) gouty arthropathy.
Patients on dialysis were excluded, but patients with chronic kidney disease stages G1 to G4 could be enrolled in the trial.
Allocation
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.
Measurment
serum urate, sitting BP and estimated glomerular filtration rate(eGFR)
Data Analysis
All comparisons were made using a nonparametric 2 sample Kruskal Wallis statistic ./所有比较均使用非参数二样本K-W秩和检验进行分析。
When multiple comparisons were performed, the Bonferroni adjustment was used in the context of a General Linear Model. /当进行多重比较时，Bonferroni校正用于一般线性回归模型进行分析。
Changes over time were also analyzed by linear regression./线性回归模型用于分析评估随时间的变化结果。
Adjusted propensity score analysis was used to assess the impact of baseline paraments on the likelihood of decreasing mean arterial pressure./调整倾向评分分析用于评估基线参数对降低平均动脉压的影响。
Results
BP Respnses
Mean MAP was decreased by 5.0 mmHg from baseline to 6 months in the q2w responders, while MAP values for q4w responders, patients who did not have persistent urate lowering (nonresponders) to q2w and q4w pegloticase and those who received placebo did not change significantly between baseline and the end of 6 months of treatment.
Lack of Change in eGFR
In this short-term (6 months) study, there was no change in eGFR in any of the groups.
Additional Assessments
There was no association between MAP decrease and other baseline patient characteristics.
Discussion
The impact of q2w pegloticase on urate levels is significantly greater in q2 responders than others, arguing that persistent and consistent lowering of serum urate may be necessary to manifest an effect on BP.
No changes in eGFR were observed, suggesting the BP effects were independent of eGFR and UA may have a direct effect on BP.
Mechanisms other than improvement in renal function may underlie the reduction in BP observed in gout patients treated with pegloticase, and there is evidence that urate reduction has potential BP-lowering effects that may not involve the kidney.
Limitations
It was a post hoc analysis, and we did not control for changes in BP medications during the trial.Prospective, double-blind placebo-controlled trials on the effect of pegloticase on BP and cardiovascular outcomes are needed.
