A Comparison of Single Dose Rasburicase 3 Mg Versus 6 Mg for the Management of Tumor Lysis Syndrome

Abstract

Introduction: Rasburicase, a recombinant form of urate oxidase, is a highly effective treatment for tumor lysis syndrome (TLS). Although the FDA-approved dose for rasburicase is 0.2 mg/kg/day for up to five days, many centers have adopted alternative dosing strategies to decrease cost, the most common being a single 6 mg dose. We hypothesized that further reducing the dose to 3 mg would result in similar efficacy and yield significant cost savings compared to the 6 mg dose strategy. Methods: We conducted a retrospective cohort study to examine the comparative effectiveness of a single 3 mg dose of rasburicase versus a single 6 mg dose in 108 adults with hematological malignancies presenting with a baseline uric acid (UA) ≤ 12 mg/dL between June 2009 and February 2015. Prior to January 2012, our institutional policy recommended a single 6 mg dose for all patients who met criteria for rasburicase for TLS. In January 2012, the policy was amended to recommend a single 3 mg dose for patients with a baseline UA ≤ 12 mg/dL. Thus, the study included 56 patients with UA ≤ 12 who received a single 6 mg dose prior to the policy modification and 52 patients with UA ≤ 12 given the 3 mg dose after the amendment. The primary endpoint was the percentage of patients who achieved a UA ≤ 8 mg/dL (the upper limit of normal at our institution) 24 hours after a single dose of rasburicase. Fisher's exact test was used to analyze categorical variables and t-tests were used to analyze continuous variables. The a priori level of significance was set at α < 0.05. Results: The mean baseline UA was 9.3 mg/dL and 9.8 mg/dL in the 3 mg arm and 6 mg arm, respectively (P = .19). At 24 hours there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL (92% vs. 98%; P = 0.36). In addition, there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL at 48 hours (98% vs. 100%; P = 0.48). Six (11.5%) patients in the 3 mg arm and one (1.8%) patient in the 6 mg arm required a second dose of rasburicase to achieve a UA <8 mg/dL (P = 0.1). Of note, the 6 mg group had a greater percent reduction in UA from baseline compared to the 3 mg group at both 24 hours (-68.1% vs. -48.6%; P < .01) and 48 hours (-69.3% vs. -51.3%; P = 0.02) after rasburicase administration. There was no difference in the percent change of serum creatinine between the two dosing strategies at 24 hours (-6.5% vs. 0.1%; P = 0.11) or 48 hours (-4.5% vs. -2.5%; P = 0.22). In addition, no difference was observed with respect to the percent of patients who required renal replacement therapy within 7 days of rasburicase administration (8.9% vs. 9.6% P = 1.0). Based on the average wholesale price of $815 for one 1.5 mg vial of rasburicase, the single 3 mg dose was associated with approximately $1,500 cost savings per encounter compared to the 6 mg dose. Conclusion: A single 3 mg dose of rasburicase was as effective as 6 mg in normalizing UA within 24 hours. Our findings demonstrate that administering a single 3 mg dose of rasburicase is a cost-effective alternative for TLS management in patients with hematological malignancies presenting with a UA ≤ 12 mg/dL. Disclosures Svoboda: Immunomedics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding. Ganetsky:Onyx: Speakers Bureau.

The efficacy and cost-impact of rasburicase 3 mg versus 6 mg for the management of tumor lysis syndrome: A multicenter analysis

“…Despite this, there was no difference in SCr and corresponding percent change in SCr at 24-h between the two arms, confirming the results of Kraus et al n an African American population. 5…”

“…5,6 A previous study conducted by Kraus et al found that, at 24 h, a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid levels were ≤ 12 mg/dL. 5…”

“…4 While the Food and Drug Administration (FDA)-approved dose is 0.05 to 0.2 mg/kg once daily for up to 7 days, several studies have shown that a single, fixed dose of rasburicase effectively decreases uric acid levels to 8 mg/dL or below, and is now the most common dosing strategy. 1,[4][5][6] Single, fixed-doses of rasburicase 3 mg, 6 mg, and 7.5 mg have been evaluated and have been shown to be efficacious in reducing uric acid levels. 5,6 A previous study conducted by Kraus et al found that, at 24 h, a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid levels were ≤ 12 mg/dL.…”

“…1,[4][5][6] Single, fixed-doses of rasburicase 3 mg, 6 mg, and 7.5 mg have been evaluated and have been shown to be efficacious in reducing uric acid levels. 5,6 A previous study conducted by Kraus et al found that, at 24 h, a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid levels were ≤ 12 mg/dL. 5 Based on a wholesale acquisition cost of $2774 per 1.5 mg vial, there is a financial interest to use the lowest effective dose.…”

“…5,6 A previous study conducted by Kraus et al found that, at 24 h, a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid levels were ≤ 12 mg/dL. 5 Based on a wholesale acquisition cost of $2774 per 1.5 mg vial, there is a financial interest to use the lowest effective dose. 7 Here, we present a multi-center analysis of level-based rasburicase utilization and its effect on healthcare costs.…”