AB1057 EFFICACY AND SAFETY OF LOW-DOSE RASBURICASE IN COMBINATION WITH CONVENTIONAL URATE-LOWERING THERAPY FOR REFRACTORY CHRONIC GOUTY ARTHRITIS: A PILOT STUDY IN

Abstract

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 defned as serum urate level was still more than 300μmol/L and dual-energy CT showed the volume of urate more than 10 cm3, 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: 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 fares 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) cm3 (Table 1). Urate level after the rasburicase add-on treatment was signifcantly 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. 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) cm3 (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). 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 creati-nine spontaneously returned to the baseline level during follow-up. 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.