Kidney Week

Abstract: PO2117

Pegloticase for Uncontrolled Gout in Kidney Transplant Recipients: Provisional Data Report of a Multicenter, Open-Label, Efficacy and Safety Study

Session Information

• Transplantation: Clinical - Underrecognized Risk Factors, Traditional Considerations, and Outcomes
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1902 Transplantation: Clinical

Authors

• Abdellatif, Abdul A., Baylor College of Medicine, Houston, Texas, United States

Abdul A. Abdellatif, MD, FASN

• Zhao, Lin, Horizon Therapeutics plc, Deerfield, Illinois, United States

Lin Zhao,

• Peloso, Paul M., Horizon Therapeutics plc, Deerfield, Illinois, United States

Paul M. Peloso,

• Cherny, Katya, Horizon Therapeutics plc, Deerfield, Illinois, United States

Katya Cherny,

• Marder, Brad, Horizon Therapeutics plc, Deerfield, Illinois, United States

Brad Marder,

• Scandling, John D., Stanford University School of Medicine, Stanford, California, United States

John D. Scandling,

• Saag, Kenneth G., University of Alabama at Birmingham, Birmingham, Alabama, United States

Kenneth G. Saag,

Background

Kidney transplant (KT) recipients have a high prevalence and severity of gout. Pegloticase (pegylated recombinant uricase) rapidly metabolizes urate and efficacy is not impacted by CKD stage. Immunomodulator co-therapy with pegloticase has improved treatment response rates over phase 3 monotherapy trials by attenuating anti-drug antibodies (ADAs). This ongoing Phase 4 trial (PROTECT NCT04087720) examines safety and efficacy of pegloticase in KT patients with uncontrolled gout (UCG).

Methods

KT recipients with UCG (serum urate [SU]≥7 mg/dL, intolerance/inefficacy to urate lowering therapy, and ≥1 of the following: tophi, chronic gouty arthritis, ≥2 flares in past yr) and functioning KT graft (eGFR≥15 ml/min/1.73m²) on stable immunosuppressive (IMS) therapy are included (KT>1 y earlier). Pegloticase (8mg q2w for 24wks) safety and efficacy are examined. Primary endpoint was SU responders during Month 6 (SU <6 mg/dL for ≥80% of time). Health Assessment Questionnaire (HAQ) pain (most severe: 100) and Disability Index (HAQ-DI) scores (max: 3) were evaluated.

Results

20 patients enrolled (mean±SD; age: 53.9±10.9 y, time since KT: 14.7±6.9 y, SU: 9.4±1.5 mg/dL, gout duration: 8.4±11.6 y; all on ≥2 IMS). At the time of analysis, 10 patients completed treatment, 3 discontinued study, 2 met SU monitoring rules (pre-dose SU>6 mg/dL at 2 consecutive visits) and discontinued pegloticase, and 5 were ongoing. All patients experienced initial substantial reductions in SU, which was maintained in the majority; 2 patients met monitoring rules. At week 24, no notable eGFR changes were observed. In patients that completed treatment, HAQ-pain and HAQ-DI scores improved by 26.7±30.3 (baseline: 35.9±30.2) and 0.2±0.5 (baseline: 1.0±1.0), respectively, at Week 24 (n=10). 7 SAEs (2 cellulitis, duodenal ulcer, sepsis, a-fib, diverticulitis, and localized infection) deemed unrelated to pegloticase, were reported in 5 patients. No anaphylaxis or IR events have occurred.

Conclusion

Preliminary results from the PROTECT trial, with Fall 2021 completion, demonstrate substantial and sustained SU decrease in the majority of KT recipients with uncontrolled gout. These findings are consistent with other reports on the effect of immunomodulation use with pegloticase.

Funding

• Commercial Support – Horizon Therapeutics plc