Background: Recombinant uricase such as pegloticase are indicated for chronic gouty arthritis who have failed to achieve serum urate level <300μmol/L even though receiving conventional urate-lowering drugs. Rasburicase which is currently approved at a dosage of 0.2 mg/(kg.d) for 5 days for the prevention of tumor lysis syndrome in pediatric patients with hematological tumors, is the only available uricase in China at present.

Objectives: To evaluate the efficacy and safety of low-dose rasburicase in refractory chronic gouty arthritis.

Methods: We retrospectively collected data of 17 patients with refractory chronic gouty arthritis who were treated with rasburicase from January 2021 to September 2021 at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The refractory chronic gouty arthritis was defined as serum urate level was still more than 300μmol/L and dual-energy CT showed the volume of urate more than 10 cm ³ , even though the allopurinol, febuxostat, and/or benzbromarone of the maximum tolerable amount were received for more than 3 months. Rasburicase was added every four weeks (week 0, week 4, and week 8) with a dosage of 1.5 mg/d for three consecutive days, on the basis of daily oral urate-lowering drugs of the maximum tolerable amount. The serum urate level was monitored. The primary outcome was the change in urate volume at week 12 compared to week 0 by dual-energy CT.

Results: ① Seventeen patients were recruited with 16 males (94%) and mean age 47±15 years old. The median gout course was 11 (6.5, 15) years with gout flares number 20 (11, 36) times in the previous year. At week 0 before the rasburicase add-on treatment, the mean serum urate was 652±94μmol/L and the median urate volume was 44 (21, 215) cm ³ (Table 1). ② Urate level after the rasburicase add-on treatment was significantly decreased than that before the treatment either at week 0, week 4, or week 8 ( Figure 1A , all p < 0.001). The median reduction of serum urate were 565 (446, 621) at week 4, 214 (57, 373) at week 8, and 118 (21, 185) at week 12 (all p <0.017). Five cases (29%) showed serum urate lower than 300μmol/L at week 12. ③ The urate volume decreased at week 12 compared to week 0 in all patients ( Figure 1B~D ). The median volume of urate reduction was 24 (12, 60) cm ³ ( p <0.001) and the median percentage of urate reduction 42% (25%, 66%). Urate reduction volume was positively correlated with baseline urate volume ( r =0.890, p <0.001), while the percentage of urate reduction volume negatively correlated with baseline urate volume ( r =-0.689, p =0.002). ④ Rasburicase was generally well tolerated. No gout attack occurred on the basis of intravenous methylprednisone 20mg before each rasburicase add-on treatment and oral colchicine 0.5mg/d to 1mg/d. No hypersensitive reaction occurred during the treatment. Phlebitis occurred in a patient (6%), while dizziness and nausea occurred in two patients (13%). One patient (6%) who was suffering chronic kidney disease of stage 3 developed acute kidney injury after rasburicase injection at week 0 and week 8, but the serum creatinine spontaneously returned to the baseline level during follow-up.

Figure 1.

The serum urate and urate volume before and after rasburicase add-on treatment. A: Paired comparison of serum urate level before and after each time of rasburicase administration; B. Reduction value and percentage of urate volume at week 12 for each patient. C&D: Dual-energy CT (DECT) showed a dramatical reduction in urate volume from week 0 (C, urate volume: 72.15 cm3) to week 12 (D, urate volume: 7.66 cm3). ***: p< 0.001; #: Received rasburicase at week 0 only; ##&###: Received rasburicase 7.5mg at week 0.

Conclusion: This pilot study shows rasburicase is well tolerated in patients with refractory chronic gouty arthritis and may be a reasonable option to effectively lower the urate burden of these patients, although this is an off-label use. Further prospective randomized controlled studies to verify the efficacy and safety are needed.

Funding: This study was funded by Yat-sen Clinical Research Project.

Disclosure of Interests: None declared