ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

ASN / Education & Meetings / Kidney Week /

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: SA-PO505

Blood Pressure Changes with Intensive Urate Lowering in Uncontrolled Gout Patients with and Without CKD

Session Information

Category: Hypertension and CVD

  • 1602 Hypertension and CVD: Clinical

Authors

  • Marder, Brad Allan, Horizon Therapeutics plc, Deerfiled, Illinois, United States
  • Johnson, Richard J., University of Colorado, Aurora, Colorado, United States
  • Choi, Hyon, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Obermeyer, Katie L., Horizon Therapeutics plc, Deerfiled, Illinois, United States
  • LaMoreaux, Brian, Horizon Therapeutics plc, Deerfiled, Illinois, United States
  • Lipsky, Peter E., AMPEL BioSolutions LLC, Charlottesville, Virginia, United States
Background

Hypertension rate is high in uncontrolled gout (UCG) patients (pts) and associated with gout and hyperuricemia. In adults, allopurinol had little effect on BP, but intensive urate-lowering with pegloticase reduced systolic (SBP) and diastolic (DBP) BP. BP changes during pegloticase use (MIRROR RCT trial) were examined.

Methods

UCG pts (SU≥7mg/dL, oral ULT failure/intolerance, and ≥1 gout symptom) were randomized 2:1 to oral MTX (15mg/wk) or PBO as cotherapy to pegloticase (8mg biweekly, 52wks). After 2wk MTX tolerance period and 4wk MTX/PBO Run-in, pts began pegloticase+MTX/PBO (Day 1). Sitting BP was measured before MTX (baseline [BL, Wk -6]) and pegloticase (Wk -4, Day1) exposure and every 2wks thereafter. Preinfusion, on-treatment BP data were included. Mean(±SD) change from BL (CFB) was examined by treatment group and BL eGFR (<60, ≥60ml/min/1.73m2).

Results

152pts (89% men, 55±13yrs, 14±11yr gout history, 76% tophi, 11±14flares/yr) were randomized (100 MTX, 52 PBO). Groups were similar at BL, including SBP (MTX vs PBO: 133±13 vs 131±15mmHg) and DBP (82±9 vs 83±10mmHg). SBP initially decreased in both groups but more in MTX pts by Wk24 (CFB: -6±16 vs -1±18mmHg). CFB was sustained in MTX pts thru Wk52, but fluctuated after Wk24 in PBO pts (n≤19; Figure). In MTX pts, DBP was below BL thru Wk52 (CFB: -2±8mmHg). In PBO pts, DBP first declined, but returned to BL by Wk52 (CFB: +1±12mmHg). Pts with BL eGFR≥60 (SBP: 133±13mmHg, DBP: 83±9mmHg; N=98) and <60 (130±15mmHg, 80±7mmHg; N=46) had similar BP CFB early in treatment but by Wk24 was more pronounced in ≥60 group (trend persisted thru Wk52, Figure).

Conclusion

BP decreased during pegloticase therapy in CKD and nonCKD pts. After 6mo, pts cotreated with MTX and without CKD had more pronounced changes. These data support a possible role of urate, and potentially MTX, in regulating BP particularly in nonCKD pts with gout. Further study is needed.

Figure. Mean change from baseline (before MTX, Wk -6) in BP during biweekly pegloticase (8 mg) treatment.

Funding

  • Commercial Support – Horizon Therapeutics plc