Broadwell Aaron, Albert John A, Padnick-Silver Lissa, LaMoreaux Brian
Rheumatology and Osteoporosis Specialists, Shreveport, LA, USA.
Rheumatic Disease Center, Milwaukee, WI, USA.
Rheumatol Ther. 2022 Dec;9(6):1549-1558. doi: 10.1007/s40744-022-00492-3. Epub 2022 Sep 22.
Patients with uncontrolled/refractory gout have heavy disease burden, but few treatment options. Pegloticase lowers serum urate (SU), but anti-drug antibodies can limit treatment efficacy. Evidence supports immunomodulator-pegloticase co-administration to increase sustained urate-lowering rates, but published cases are limited. This study investigated experience with pegloticase-immunomodulation co-therapy at two community rheumatology practices.
Patients initiating pegloticase with immunomodulation in 2017 or later were included. Patient/treatment characteristics and proportion of responders (≥ 12 pegloticase infusions, SU < 6 mg/dl at infusion-12) were examined. Patients on therapy at data collection with < 12 infusions were excluded from response analyses. eGFR before and after therapy was examined.
Thirty-four patients (79% male, 62.4 ± 16.3 years) with uncontrolled gout (SU = 9.1 ± 2.0 mg/dl, 91% tophaceous) were included. Most-reported comorbidities were hypertension (76%), obesity (71%), osteoarthritis (68%), and CKD (47%). Pre-therapy eGFR was 65.4 ± 25.2 ml/min/1.73 m (41% eGFR < 60 ml/min/1.73 m). All patients initiated immunomodulation before (5.3 ± 3.0 weeks, n = 32) or at (n = 2) first pegloticase infusion. Subcutaneous methotrexate (15.4 ± 4.9 mg/week, n = 20), oral methotrexate (15.3 ± 3.6 mg/week, n = 9), mycophenolate mofetil (1000 mg/day, n = 3), and azathioprine (100 mg/day, n = 2) were administered. Patients received 14.6 ± 7.1 infusions over 28.5 ± 14.9 weeks. Overall response rate was 89%, ranging among immunomodulators (subcutaneous methotrexate: 93%, oral methotrexate: 89%, mycophenolate mofetil: 100%, azathioprine: 50%). On average, eGFR increased during therapy (+ 10.3 ± 16.9 ml/min/1.73 m), with CKD stability/improvement in 85%. Nineteen patients (56%) experienced gout flares. No infusion reactions or infections were noted. No new safety concerns were identified.
These real-world findings provide further support for increased pegloticase response rates when co-treatment with immunomodulating therapy is used.
痛风控制不佳/难治性痛风患者疾病负担沉重，但治疗选择有限。聚乙二醇化尿酸酶可降低血清尿酸（SU）水平，但抗药物抗体可能会限制治疗效果。有证据支持联合使用免疫调节剂和聚乙二醇化尿酸酶以提高尿酸持续降低率，但已发表的病例有限。本研究调查了两家社区风湿病诊所使用聚乙二醇化尿酸酶 - 免疫调节联合疗法的经验。
纳入2017年或之后开始接受聚乙二醇化尿酸酶免疫调节治疗的患者。检查患者/治疗特征及缓解者比例（≥12次聚乙二醇化尿酸酶输注，输注12次后SU＜6mg/dl）。数据收集时接受治疗但输注次数＜12次的患者被排除在缓解分析之外。检查治疗前后的估算肾小球滤过率（eGFR）。
纳入34例痛风控制不佳的患者（79%为男性，年龄62.4±16.3岁）（SU = 9.1±2.0mg/dl，91%有痛风石）。最常报告的合并症为高血压（76%）、肥胖（71%）、骨关节炎（68%）和慢性肾脏病（47%）。治疗前eGFR为65.4±25.2ml/min/1.73m²（41%的患者eGFR＜60ml/min/1.73m²）。所有患者在首次聚乙二醇化尿酸酶输注前（5.3±3.0周，n = 32）或输注时（n = 2）开始免疫调节治疗。给予皮下甲氨蝶呤（15.4±4.9mg/周，n = 20）、口服甲氨蝶呤（15.3±3.6mg/周，n = 9）、霉酚酸酯（1000mg/天，n = 3）和硫唑嘌呤（100mg/天，n = 2）。患者在28.5±14.9周内接受了14.6±7.1次输注。总体缓解率为89%，不同免疫调节剂的缓解率有所不同（皮下甲氨蝶呤：93%，口服甲氨蝶呤：89%，霉酚酸酯：100%，硫唑嘌呤：50%）。治疗期间eGFR平均升高（+10.3±16.9ml/min/1.73m²），85%的慢性肾脏病患者病情稳定/改善。19例患者（56%）出现痛风发作。未观察到输注反应或感染。未发现新的安全问题。
这些真实世界的研究结果为联合免疫调节治疗提高聚乙二醇化尿酸酶反应率提供了进一步支持。
