Clinical transplantation · 2023
Pegloticase efficacy and safety in kidney transplant recipients; results of the phase IV, open-label PROTECT clinical trial.
Клиническое исследование IV фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Abdellatif Abdul, Zhao Lin, Chamberlain Jason, Cherny Katya, Xin Yan, Marder Brad A, Scandling John D, Saag Kenneth
Аннотация
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 ≥7 mg/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] ≥15 mL/min/1.73 m2 ) on stable immunosuppression therapy.
RESULTS: The primary endpoint was sUA response during month 6 (sUA < 6 mg/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 ± 1.5 mg/dL, gout duration: 8.4 ± 11.6 years; all on ≥2 stable doses of immunosuppression agents. Pegloticase (8 mg intravenous every 2 weeks) 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.
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 ≥7 mg/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] ≥15 mL/min/1.73 m2 ) on stable immunosuppression therapy.
RESULTS: The primary endpoint was sUA response during month 6 (sUA < 6 mg/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 ± 1.5 mg/dL, gout duration: 8.4 ± 11.6 years; all on ≥2 stable doses of immunosuppression agents. Pegloticase (8 mg intravenous every 2 weeks) 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.