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

BackgroundRecombinant 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.ObjectivesTo evaluate the efficacy and safety of low-dose rasburicase in refractory chronic gouty arthritis.MethodsWe 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 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.Results① 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) cm3 (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) 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). 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.ConclusionThis 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.FundingThis study was funded by Yat-sen Clinical Research Project.Disclosure of InterestsNone declared