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Kidney Week

Abstract: FR-PO232

Pharmacokinetics and Immunogenicity of Pegloticase in Patients With Kidney Transplants Receiving Pegloticase for Uncontrolled Gout

Session Information

  • Pharmacology
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

  • 1900 Pharmacology (PharmacoKinetics‚ -Dynamics‚ -Genomics)

Authors

  • Abdellatif, Abdul A., Baylor College of Medicine, Nephrology and CLS Health, Houston, Texas, United States
  • Xin, Yan, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Chamberlain, Jason, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Zhao, Lin, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Cherny, Katya, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Marder, Brad Allan, Horizon Therapeutics plc, Deerfield, Illinois, United States
  • Scandling, John D., Stanford Medicine, Division of Nephrology, Stanford, California, United States
  • Saag, Kenneth G., The University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, United States
Background

Immunomodulator co-therapy with pegloticase markedly improves the efficacy of pegloticase by reducing its immunogenicity.1-4 PROTECT (NCT04087720), an open-label, single-arm study in uncontrolled gout patients with a history of kidney transplant (KT) on stable immunosuppressants demonstrated that pegloticase was effective in reducing serum urate (SU) levels, with a high (89%) responder rate, defined as SU < 6 mg/dL for ≥80% of the time during month 6, while preserving key graft function indicators.5 The objective of this study was to evaluate the pharmacokinetics (PK) and immunogenicity of pegloticase in uncontrolled gout patients with a history of KT on immunosuppression.

Methods

Pegloticase (8 mg infusion [IV]) was administered every two weeks (q2w) for 24 weeks. Serum samples for PK and immunogenicity analysis were collected pre- and post-dose at multiple visits.

Results

20 patients received at least 1 dose of pegloticase and were included in the analysis. Measurable pegloticase concentrations were maintained in SU responders through Month 6. Following treatment initiation, the median pre- and post-dose pegloticase concentration ranged from 0.97 to 1.59 µg/mL and 1.57 to 3.60 µg/mL respectively across visits. In contrast, the 2 non-responders both had pre-dose pegloticase concentrations below the limit of quantification (BLQ), and one had a BLQ value post-pegloticase infusion, which was consistent with the immunogenicity results. Pegloticase exposures were higher than those observed with pegloticase monotherapy, which was consistent with the improved PK results observed with methotrexate co-therapy. No infusion reactions or anaphylaxis occurred during the trial.

Conclusion

Pegloticase 8 mg IV q2w with standard of care immunosuppressants in transplant patients resulted in a high SU responder rate and improved pegloticase exposure.

References:
1. Keenan RT, et al. Seminars in Arthritis and Rheumatism 2021; 51:347-352
2. Botson J, et al. J Rheumatol 2021;48:767-74
3. Song Y, et al. Arthritis Rheum 2020;72(suppl 10)
4. Xin Y, et al. EULAR 2022; POS1163
5. Abdellatif A., et al. Amer Soc Neph; 2021, Abstract PO1127.