Quality of life improvements and clinical assessments in kidney transplant recipients undergoing pegloticase treatment for uncontrolled gout: findings of the phase 4 PROTECT clinical trial

接受培洛替酶治疗的肾移植受者在控制性痛风方面的生活质量改善和临床评估:4期PROTECT临床试验的结果

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Abstract

INTRODUCTION: Gout is 12-times more prevalent in kidney transplant (KT) recipients than in non-transplanted population. We report quality-of-life (QOL) and clinical assessment findings from the PROTECT trial examining pegloticase efficacy and safety in KT recipients with uncontrolled gout. METHODS: Patients with serum urate (SU) ≥7 mg/dL, oral urate-lowering therapy refractory/intolerant, and with one of the following were enrolled: ≥2 flares/year, unresolving tophi, or chronic gouty arthritis. Patients were ≥1 year post-transplant, with a graft eGFR ≥15 ml/min/1.73m(2) and received stable immunosuppression. Pegloticase was administered for 24 weeks. QOL endpoints included the Health Assessment Questionnaire (HAQ; Disability Index [DI], Health, Pain) and Physician Global Assessment (PhGA) of Gout. Key clinical assessments included proportion of patients with resolution of ≥1 tophus and change from baseline in blood pressure (BP) at Week 24. RESULTS: Twenty KT recipients (85.0% male, age: 53.9±10.9 years, BMI: 30.6±7.2 kg/m(2), eGFR: 45.8±11.9 ml/min/1.73 m(2), time since kidney transplant: 14.6±6.9 years) were included. The primary endpoint was achieved with 89% of patients reaching and maintaining a SU of <6 mg/dL during Month 6. Meaningful improvements occurred over 24 weeks of treatment in all QOL measures (mean [95% CI] change from baseline: HAQ-DI: -0.3 [-0.6, 0.1], HAQ-Pain: -35.5 [-54.5, -16.5], HAQ-Health: -22.4 [-39.5, -5.2], PhGA: -2.4 [-3.7, -1.1]) and clinical assessments (≥1 tophus resolved: 3 of 7 with tophi at baseline [42.9%]; change from baseline in mean arterial BP: -6.8 [-12.5, -1.0] mmHg). CONCLUSIONS: Given the high prevalence of uncontrolled gout in KT recipients, proper SU management is of particular importance. Additionally, intensive urate-lowering with pegloticase may have clinical and QOL benefits.

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