Abstract

INTRODUCTION: Kidney transplant (KT) recipients have a high prevalence and severity of gout. Pegloticase (pegylated recombinant uricase) rapidly metabolizes serum uric acid (sUA), and its efficacy is not impacted by kidney function.METHODS: This open-label, Phase 4 trial (PROTECT NCT04087720) examined safety and efficacy of pegloticase in 20 participants with KT>1 year prior to enrollment and with uncontrolled gout (sUA =7mg/dL, intolerance/inefficacy to urate lowering therapy, and =1 of the following: tophi, chronic gouty arthritis, =2 flares in past year) and functioning KT (estimated glomerular filtration rate [eGFR] =15mL/min/1.73 m2 ) on stable immunosuppression therapy.RESULTS: The primary endpoint was sUA response during month 6 (sUA<6mg/dL for =80% of time). The study enrolled 20 participants (mean±SD); age: 53.9±10.9 years, time since KT: 14.7±6.9 years, sUA: 9.4±1.5mg/dL, gout duration: 8.4±11.6 years; all on =2 stable doses of immunosuppression agents. Pegloticase (8mg intravenous every 2weeks) in KT recipients with uncontrolled gout showed a high response rate of 89% (16/18 responders). Two participants discontinued treatment solely due to COVID-19 concerns prior to month 6 were not included in the primary analysis. Pegloticase exposures were higher than those historically observed with pegloticase monotherapy, and no anaphylaxis or infusion reaction events occurred during the study.CONCLUSIONS: This improved response rate to pegloticase in the KT population reflects observations from other trials and reports on immunomodulation with pegloticase. As the KT population has a high prevalence of gout and limitations with oral urate lowering medication options, these findings suggest a potential option for uncontrolled gout therapy in KT participants.

View details for DOI 10.1111/ctr.14993

View details for PubMedID 37138473