Abstract: FR-PO582

Pegloticase, a Mammalian Uricase, Significantly Decreases Mean Arterial Blood Pressure in Patients with Chronic Gout

Session Information

Category: Hypertension

  • 1106 Hypertension: Clinical and Translational - Secondary Causes

Authors

  • Lipsky, Peter E, AMPEL BioSolutions, Charlottesville, Virginia, United States
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
  • Choi, Hyon, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Yeo, Anthony, AMPEL BioSolutions, Charlottesville, Virginia, United States
Background

Hypertension is a recognized co-morbidity of hyperuricemia and gout,1 and there are significant correlations between serum uric acid (sUA) and blood pressure (BP) in individuals with and without gout.1 While some studies suggest lowering sUA may decrease BP,2 a meta-analysis indicated no consistent effect of oral urate lowering therapy.3 Pegloticase persistently decreases sUA to <1 mg/dL in responders.4 Results from the pegloticase randomized clinical trials (RCTs) permitted determination of the impact of persistent, very low sUA levels on BP in subjects with chronic refractory gout.

Methods

This analysis used results from two 6-month RCTs in which subjects received 8 mg pegloticase every 2 weeks or placebo.4 sUA responders maintained sUA <6 mg/dL and usually <1mg/dL.4 Sitting BP was measured at each visit and estimated glomerular filtration rate (eGFR) was determined at baseline and after 3 and 6 months.

Results

29 sUA responders were assessed and their mean arterial pressure (MAP) at baseline was 94.9 ± 9.6 mm Hg. At baseline, 36%, 18%, 18%, 25%, and 4% of patients were in CKD eGFR categories G1, G2, G3a, G3b, and G4, respectively. There were significant reductions in MAP in responders throughout the 6-month trial (P=0.0029), with significant changes noted within 2 weeks of the first pegloticase dose. No consistent pattern of MAP decrease was noted in non-responders or subjects receiving placebo. Of the 29 sUA responders, 18 (62.1%) had persistent decreases in MAP. There were no significant differences in baseline age, gender, race, BMI, documented history of hypertension, duration of gout, MAP, sUA, cholesterol, eGFR or urinary uric acid /creatinine ratio in those who decreased MAP vs those who did not. There were no significant changes in eGFR in sUA responders to pegloticase and no significant correlation between changes from baseline MAP and eGFR in these subjects (r= -0.16, P=0.43).

Conclusion

sUA responders to pegloticase experienced significant reductions in MAP that were independent of changes in renal function.



1. Essex MN, J Clin Rheumatol. 2017;23:160.
2. Agarwal V, et al. J Clin Hypertens. 2013;15:435.
3. Franca GPH, deMoraes SER. Cochrane Database of Systematic Reviews 2017, 4:CD008652.
4. Sundy JS, et al. JAMA. 2011;306:711.

Funding

  • Commercial Support