Changes in Blood Pressure With Urate-Lowering in Uncontrolled Gout

Among patients with uncontrolled gout, the rate of hypertension is high and associated with hyperuricemia and gout. Allopurinol had little effect on blood pressure in adults; however, there were reductions in systolic and diastolic blood pressure with intensive urate-lowering with pegloticase.

Brad A. Marder and colleagues conducted an analysis of changes in blood pressure during pegloticase use in the randomized, controlled MIRROR trial. Results were reported during a poster session at the American Society of Nephrology Kidney Week 2023 in a poster titled Blood Pressure Changes With Intensive Urate Lowering in Uncontrolled Gout Patients With and Without CKD.

Uncontrolled gout was defined as serum urate 7 mg/dL, failure of or intolerance to oral urate-lowering therapy, and one or more gout symptoms. In the MIRROR trial, patients with uncontrolled gout were randomized 2:1 to oral methotrexate (MTX; 15 mg/week) or placebo as cotherapy to pegloticase (8 mg biweekly for 52 weeks).

Following a 2-week MTX tolerance period and a 4-week MTX/placebo run-in period, patients were initiated on pegloticase plus MTX or pegloticase plus placebo (day 1). Sitting blood pressure was measured prior to MTX (baseline, week 6) and pegloticase exposure (week 4, day 1) and every 2 weeks thereafter. Data on preinfusion and on-treatment blood pressure were included. The mean change in blood pressure from baseline was examined by treatment group and baseline estimated glomerular filtrate rate (eGFR; <60 mL/min/1.73 m² vs ≥60 mL/min/1.73 m²).

The analysis included 152 patients; 80% were men, mean age was 55 years, mean history of gout was 14 years, mean gout tophi was 76%, and mean number of gout flares per year was 11. At baseline, the groups were similar in clinical characteristics, including systolic blood pressure (MTX, 133 mm Hg vs placebo, 131 mm Hg) and diastolic blood pressure (82 mm Hg vs 83 mm Hg, respectively).

In both groups, blood pressure decreased initially but decreased more in the MTX group by week 24 (change from baseline, –6 mm Hg vs –1 mm Hg). Change from baseline was sustained in patients in the MTX group through week 52 but fluctuated after week 24 in the placebo group. In the MTX group, diastolic blood pressure was below baseline through week 52. In the placebo group, diastolic blood pressure initially declined but returned to baseline by week 52.

Early in treatment, patients with baseline eGFR <60 mL/min/1.73 m² and ≥60 mL/min/1.73 m² had similar change from baseline. However, by week 24, the change from baseline was more pronounced in the group with eGFR ≥60 mL/min/1.73 m², a trend that persisted through week 52.

In summary, the authors said, “Blood pressure decreased during pegloticase therapy in chronic kidney disease (CKD) and non-CKD patients. After 6 months, patients cotreated with MTX and without CKD had more pronounced changes. These data support a possible role of urate, and potentially MTX, in regulating blood pressure, particularly in non-CKD patients with gout. Further study is needed.”

Source: Marder BA, Johnson RJ, Choi H, Obermeyer KL, LaMoreaux B, Lipsky PE. Blood pressure changes with intensive urate lowering in uncontrolled gout patients with and without CKD. SA-PO505. Abstract of a poster presented at the American Society of Nephrology Kidney Week 2023; November 4, 2023; Philadelphia, Pennsylvania. Funding for this analysis was provided by Horizon Therapeutics plc.