A Clinical and Economic Comparison of Rasburicase and Allopurinol in the Treatment of Patients With Clinical or Laboratory Tumor Lysis Syndrome.

BACKGROUND: The aim of the study was to compare reductions in uric acid (UA), length of stay (LOS), and hospitalization costs in patients with tumor lysis syndrome (TLS) treated with rasburicase or allopurinol. PATIENTS AND METHODS: This retrospective study of administrative data included hospitalized pediatric and adult patients who had clinical or laboratory TLS and received rasburicase or allopurinol. Each rasburicase-treated patient was propensity score-matched with 4 allopurinol-treated patients. Mean changes in UA within ≤ 2 days of treatment initiation were determined. Economic outcomes included mean number of days in the intensive care unit (ICU), total LOS, costs/hospitalization, and costs/percentage change in UA. RESULTS: Twenty-six rasburicase-treated patients were matched with 104 allopurinol-treated patients. Reduction in plasma UA was 5.3 mg/dL greater for patients treated with rasburicase than for patients treated with allopurinol (P < .0001). Length of ICU stay was 2.5 days less for patients treated with rasburicase than for patients treated with allopurinol (P < .0001), and total LOS was 5 days less for patients treated with rasburicase than for patients treated with allopurinol (P = .02). Total costs per patient were $20,038 lower for patients treated with rasburicase than for patients treated with allopurinol (P < .02). Cost per percentage UA reduction was also lower for patients treated with rasburicase versus patients treated with allopurinol ($3899 vs. $16,894; P < .001). CONCLUSION: In this analysis of TLS patients who received care in real-world settings, rasburicase versus allopurinol was significantly more effective in treating hyperuricemia and was associated with significantly shorter ICU and overall hospital stays and lower total inpatient costs.

Fixed, low-dose rasburicase for the treatment or prevention of hyperuricemia in adult oncology patients.

PURPOSE: Rasburicase is a recombinant urate oxidase enzyme administered to high risk patients or to those with preexisting hyperuricemia from tumor lysis syndrome (TLS). The objective of this retrospective review is to evaluate and characterize the use of fixed, low-dose rasburicase for the treatment of hyperuricemia in adult patients. PATIENTS/METHODS: A retrospective chart review from 1 October 2005 to 31 December 2011 was conducted in adult oncology patients who received fixed, low-dose rasburicase. Patients who met the inclusion criteria were evaluated for the uric acid level change from baseline and the achievement of uric acid level less than 8 mg/dL. RESULTS: Forty-five patients were included in the analysis in which 26 (58%) patients received 3 mg rasburicase. For the 39 patients with baseline uric acid levels 8 mg/dL or higher, 80% achieved a uric acid level lower than 8 mg/dL with a single rasburicase dose. Six patients (13%) required renal replacement therapy despite rasburicase. The median uric acid level reduction 24 h post rasburicase dose 1.5 mg, 3 mg, 4.5 mg, and 6 mg were 5.5, 5.8, 3.8, and 10.05 mg/dL, respectively. There was no clinical difference between obese and non-obese patients in terms of their median uric acid reduction, 5.5 vs. 7 mg/dL, respectively. CONCLUSION: Fixed, low dose rasburicase produced a consistent lowering of uric acid levels and may be utilized in the management of hyperuricemia in TLS. Further study is necessary to determine if a larger fixed dose would be required in those patients with a higher baseline uric acid level.

Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS. METHODS: Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS. RESULTS AND DISCUSSION: Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen. WHAT IS NEW AND CONCLUSION: Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study.

Economic implications of rasburicase treatment in adult patients with tumour lysis syndrome.

BACKGROUND: Rasburicase is a recombinant urate-oxidase enzyme used to reduce high levels of plasma uric acid (PUA) resulting from tumour lysis syndrome (TLS). Rasburicase reduces PUA levels within 4 hours of administration, thereby minimizing the risk of serious complications from TLS. Treatment pattern analyses indicate rasburicase is often used in combination with allopurinol; however, no studies have evaluated the clinical and economic consequences of this pattern of care. The purpose of this study was to compare hospitalization costs, overall length of stay (LOS), and critical-care LOS in patients receiving rasburicase with or without allopurinol. METHODS: Hospital claims data from the Premier Perspective Database™ were used to conduct this retrospective analysis. Patients in the Premier hospital database who were administered rasburicase or combination therapy (rasburicase + allopurinol) within 2 days of hospital admission were eligible for study inclusion. Patients were excluded if they were <18 years of age or received haemodialysis (or any other renal replacement therapy support) on admission. Rasburicase patients were propensity-score-matched to combination therapy patients based on gender, race, hospital type (urban/rural, teaching), provider type, payer type, admission source, use of electrolyte modification therapy, critical-care admission and presence of a cancer diagnosis. Differences in healthcare costs, overall LOS and critical-care LOS were assessed using γ-distributed generalized linear models with a log-link function. RESULTS: The study population comprised 66 patients receiving rasburicase monotherapy matched to 66 patients receiving combination therapy. Mean age was 62.9 years, and 29% were female. Patients initiated on combination therapy had a shorter mean duration of rasburicase administration than patients initiated on monotherapy (2.1 vs 2.7 days) [p = 0.0059]. Additionally, rasburicase monotherapy incurred an average total cost of $US35 843 per hospitalization, compared with $US46 672 for those receiving combination therapy (p = 0.0820). Rasburicase monotherapy patients also had a shorter mean overall LOS (10.0 days vs 15.4 days; p = 0.0067). The mean critical-care LOS was similar in both cohorts (2.4 days rasburicase vs 2.9 days combination therapy; p = 0.3389). CONCLUSION: Examination of claims data showed that combination therapy (rasburicase + allopurinol) trended toward higher total hospitalization costs than rasburicase monotherapy. In addition, combination therapy was associated with significantly longer overall LOS compared with upfront rasburicase monotherapy in patients at risk for developing TLS.

Evaluation of a low, weight-based dose of rasburicase in adult patients for the treatment or prophylaxis of tumor lysis syndrome.

PURPOSE: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS. PATIENTS/METHODS: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS. RESULTS: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer's dosing recommendation. CONCLUSIONS: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

Economic comparison of rasburicase and allopurinol for treatment of tumor lysis syndrome in pediatric patients.

PURPOSE: Economic outcomes of rasburicase and allopurinol for treatment of tumor lysis syndrome (TLS) in pediatric patients were compared. METHODS: Claims data from a large hospital database were used to conduct the analysis. Pediatric patients diagnosed with TLS and administered rasburicase or allopurinol within two days of hospital admission were eligible for inclusion. Patients were excluded if they were age ≥18 years or received hemodialysis on admission. Patients receiving rasburicase were propensity score matched to allopurinol-treated patients based on sex, race, hospital type, provider type, payer type, admission source, use of electrolyte modification therapy, and comorbid diagnoses. Differences in health care costs, length of stay (LOS), and duration of subsequent critical care were assessed using γ-distributed generalized linear models with a log-link function. Results A total of 63 allopurinol-treated and 63 rasburicase-treated patients were matched in the analysis. The mean age of patients was 7.4 years, and girls comprised 27% of the sample. Rasburicase-treated patients incurred a mean cost of $30,470 per hospitalization, compared with $35,165 for allopurinol-treated patients (p = 0.427). Duration of critical care was significantly shorter for rasburicase-treated patients (1.4 days versus 2.5 days for allopurinol-treated patients, p = 0.0001); however, mean LOS did not statistically differ between groups, averaging 13.8 days for patients treated with rasburicase and 14.9 days for the allopurinol-treated group. CONCLUSION: Examination of claims from a large hospital database showed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in critical care days but not with a significant difference in mean LOS or total cost.

Single-dose rasburicase for tumour lysis syndrome in adults: weight-based approach.

BACKGROUND: The optimal rasburicase dose for adult patients has not been determined. OBJECTIVE: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. METHOD: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome-associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. RESULT: Twenty-one patients received rasburicase with an average first dose of 0.15 +/- 0.03 mg/kg. The drug dosing was calculated based on the patients' ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89.7 +/- 9.0% from the baseline through the first 24 h after a single rasburicase dose (11.4 +/- 4.5 mg/dL vs. 1.4 +/- 1.4 mg/dL, respectively, P < 0.001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer's recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24-72 h after the single rasburicase dose were not significantly different from baseline (1.8 mg/dL vs. 2.3 mg/dL, respectively, P = 0.14). CONCLUSION: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia-associated nephrotoxicity. From our experience, a single dose of 0.15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h.

Pan-European multicentre economic evaluation of recombinant urate oxidase (rasburicase) in prevention and treatment of hyperuricaemia and tumour lysis syndrome in haematological cancer patients.

GOALS: Hyperuricaemia (HU) and tumour lysis syndrome (TLS) are complications of acute myeloid/lymphoid leukaemia (AML/ALL) and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective was to assess incremental cost-effectiveness ratios (ICER) of preventing/treating HU and TLS with recombinant urate oxidase, rasburicase (Fasturtec/Elitek). PATIENTS AND METHODS: Incidence and costs of HU and TLS were based on a multi-country chart review. Life expectancy at the time of diagnosis was based on published survival rates and age at diagnosis. Reductions of HU/TLS following treatment with rasburicase were based on clinical trial data. RESULTS: Prevention with rasburicase appears highly cost-effective in children (ICER between Eur 425 and Eur 3054 per life-year saved, LYS). In adults, prevention is more cost-effective in NHL and ALL (maximum ICER of Eur 41383 and Eur 32126 per LYS). Treatment of established HU/TLS with rasburicase is cost-saving in children and highly cost-effective in adults. The results are robust in children. In adults, the prevention strategy appears sensitive to the risk of HU/TLS. CONCLUSIONS: In conclusion, rasburicase, in addition to the demonstrated clinical benefit, is an economically attractive new option in the treatment of HU, both in adults and children. In prevention the drug has an attractive economic profile in children, and is cost-effective in adults with ALL and NHL.

Incidence, medical resource utilisation and costs of hyperuricemia and tumour lysis syndrome in patients with acute leukaemia and non-Hodgkin's lymphoma in four European countries.

Hyperuricemia (HU) and tumour lysis syndrome (TLS) are complications of acute leukaemia and non-Hodgkin lymphoma (NHL) leading to increased morbidity and mortality. The objective of this study was to define incidence and calculate health care cost associated with HU and TLS. 788 acute leukaemia and NHL patients from Belgium, The Netherlands, Spain and UK were screened retrospectively for HU and TLS. Resource use related to HU and TLS was recorded and costs were calculated applying local unit costs. Results showed that HU occurred in 18.9% of patients, and 27.8% of them fulfilled TLS criteria. The cost of HU without TLS was 672 euros (SE 181), the cost of TLS 7,342 euros (SE 1,412). TLS requiring dialysis incurred an average cost of 17,706 euros. In conclusion, it is noted that the observed incidence rates were lower than earlier reports. In addition, some risk factors for HU and TLS (e.g. paediatric patients versus adults) were not associated with increased rates of HU or TLS as a consequence of higher rates of prevention. TLS cases incurred 11 times higher costs than HU cases in which TLS was absent. The main cost drivers in TLS are interventions requiring intensive care.