Rheumatic Disease Center, Milwaukee, WI.
Rheumatology and Osteoporosis Specialists, Shreveport, LA.
Medicine (Baltimore). 2024 Mar 8;103(10):e37424. doi: 10.1097/MD.0000000000037424.
Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use. This pooled case series examined pegloticase + MTX co-therapy in uncontrolled gout patients with and without CKD. Cases of pegloticase + MTX co-therapy in existing datasets were retrospectively examined. Baseline eGFR classified patients as CKD (eGFR < 60 mL/min/1.73 m2) or non-CKD (eGFR ≥ 60 mL/min/1.73 m2). Patient characteristics, treatment parameters, laboratory values, urate-lowering response rate (≥12 pegloticase infusions received and SU < 6 mg/dL just before infusion 12), and AEs were examined. Fifteen CKD (eGFR: 43.2 ± 11.3 mL/min/1.73 m2; SU: 8.6 ± 2.2 mg/dL), 27 non-CKD (eGFR: 82.9 ± 19.0 mL/min/1.73 m2; SU: 9.5 ± 1.7 mg/dL) patients were included. Comorbidity profiles were similar, but CKD patients were older (72.0 ± 9.9 vs 52.3 ± 14.3 years) and more often female (33.3% vs 7.4%). Treatment parameters were similar with 4-week MTX Run-in followed by mean of 14.7 ± 8.1 [CKD] vs 14.1 ± 7.1 [non-CKD] pegloticase infusions. However, CKD patients had lower MTX dose (14.8 ± 5.8 vs 19.3 ± 4.9 mg/week). Urate-lowering response was similar (92% vs 86%). eGFR increased during treatment in 60% of CKD (+11.5 ± 20.9 mL/min/1.73 m2, 87% stable/improved CKD-stage) and 44% of non-CKD (+4.2 ± 15.0 mL/min/1.73 m2) patients. AEs were similar (≥1 AE CKD: 53%, non-CKD: 67%; gout flare most-reported). One case each of pancytopenia and IR (mild) occurred in non-CKD patients. These real-world data show similar pegloticase + MTX efficacy in CKD and non-CKD patients. No new safety signals were identified, with most CKD patients showing renal function stability or improvement during therapy.
慢性肾病（CKD）和痛风常同时发生。聚乙二醇尿酸酶可降低未控制的痛风患者的血清尿酸（SU）水平，但抗药物抗体限制了尿酸降低的反应，并增加了输注反应（IR）的风险。甲氨蝶呤（MTX）联合治疗可提高聚乙二醇尿酸酶的反应率并降低 IR 风险，但 CKD 限制了 MTX 的使用。本病例系列研究了合并 CKD 和不合并 CKD 的未控制痛风患者中聚乙二醇尿酸酶+MTX 联合治疗的情况。回顾性分析了现有数据集中聚乙二醇尿酸酶+MTX 联合治疗的病例。根据基线 eGFR 将患者分为 CKD（eGFR＜60mL/min/1.73m2）或非 CKD（eGFR≥60mL/min/1.73m2）。检查患者特征、治疗参数、实验室值、尿酸降低反应率（接受≥12 次聚乙二醇尿酸酶输注，且在第 12 次输注前 SU＜6mg/dL）和不良反应（AE）。纳入 15 例 CKD（eGFR：43.2±11.3mL/min/1.73m2；SU：8.6±2.2mg/dL）和 27 例非 CKD（eGFR：82.9±19.0mL/min/1.73m2；SU：9.5±1.7mg/dL）患者。合并症谱相似，但 CKD 患者年龄较大（72.0±9.9 vs 52.3±14.3 岁），女性更多（33.3% vs 7.4%）。治疗参数相似，均采用 4 周 MTX 导入期，然后平均接受 14.7±8.1[CKD]vs 14.1±7.1[非 CKD]次聚乙二醇尿酸酶输注。然而，CKD 患者的 MTX 剂量较低（14.8±5.8 vs 19.3±4.9mg/周）。尿酸降低反应相似（92% vs 86%）。在治疗期间，60%的 CKD（+11.5±20.9mL/min/1.73m2，87%的 CKD 稳定/改善）和 44%的非 CKD（+4.2±15.0mL/min/1.73m2）患者的 eGFR 增加。AE 相似（≥1 例 AE CKD：53%，非 CKD：67%；痛风发作最常见）。非 CKD 患者各有 1 例出现全血细胞减少症和 IR（轻度）。这些真实世界的数据表明，聚乙二醇尿酸酶+MTX 在 CKD 和非 CKD 患者中的疗效相似。未发现新的安全性信号，大多数 CKD 患者在治疗过程中肾功能稳定或改善。
