小剂量拉布立海治疗难治性慢性痛风性关节炎的疗效及安全性

Efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis

目的评估拉布立海小剂量方案对难治性慢性痛风性关节炎的临床疗效与安全性。方法随访研究。回顾性分析2021年1月至2022年7月在中山大学孙逸仙纪念医院接受拉布立海治疗的难治性慢性痛风性关节炎患者的临床资料。所有患者均使用可耐受的最大剂量口服降尿酸药物3个月以上但血尿酸(sUA)仍>360μmol/L、双能CT尿酸盐体积>10 cm^(3)。小剂量拉布立海的使用方法为每次4.5~7.5 mg,间隔4周使用1次,最多使用3次。收集疗效(每次拉布立海用药前后sUA、第1次用药前和用药后12周痛风石及尿酸盐体积变化)和安全性数据。结果共纳入22例患者,其中男21例(95.4%),年龄(44±15)岁,病程11(6,15)年,治疗前sUA为(667±112)μmol/L。每次拉布立海治疗后,患者sUA均低于治疗前(均P<0.001),3次治疗的sUA降低值[M(Q_(1),Q_(3))]分别为568(471,635)、187(66,335)和123(49,207)μmol/L。治疗12周时,9例患者(40.9%)的sUA<360μmol/L,1例患者痛风石消失;所有患者尿酸盐体积较第1次治疗前降低明显[17(7,134)cm^(3)比40(16,172)cm^(3),P<0.001],降低百分比为41.6%(22.9%,58.5%)。总体安全性良好,无严重不良反应发生。结论小剂量拉布立海对难治性慢性痛风性关节炎安全有效,值得进一步随机对照研究。

Objective To explore the efficacy and safety of low-dose rasburicase for refractory chronic gouty arthritis.Methods A cohort study.The clinical data of patients with refractory chronic gouty arthritis who were treated with rasburicase at Sun Yat-sen Memorial Hospital,Sun Yat-sen University between January 2021 and July 2022 were retrospectively analyzed.Refractory chronic gouty arthritis was defined as serum uric acid(sUA)>360μmol/L and urate volume>10 cm^(3)under dual-energy computed tomography after tolerable maximal oral urate-lowering therapy for at least 3 months.The administration of low-dose rasburicase was applied intravenously with total dosage ranging from 4.5 to 7.5 mg each dose,at 4-week intervals for a maximum of three doses.Efficacy was evaluated by the changes of sUA level,tophus and urate volume.Results A total of 22 patients were included for analysis,with 95.4%(21/22)male,the mean age was(44±15)years,and the median duration of gout was 11(6-15)years.The mean sUA at baseline was(667±112)μmol/L.The levels of sUA significantly decreased after each dose of rasburicase(P<0.001),and the median reduction of sUA after each dose of rasburicase was 568(471-635),187(66-335)and 123(49-207)μmol/L,respectively.At week 12,nine patients(40.9%)exhibited sUA<360μmol/L and tophus disappeared in one patient.The urate volume significantly decreased at week 12 when compared with that before the first dose of rasburicase in all the patients[40(16-172)cm^(3)vs 17(7-134)cm^(3),P<0.001],with a median reduction rate of 41.6%(22.9%-58.5%).The everall safety of rasburicase was good,and no serious adverse reactions occurred.Conclusions Low-dose rasburicase is well-tolerated and effective for decreasing the urate burden in patients with refractory chronic gouty arthritis.Further prospective randomized controlled trials are needed to validate these findings.