Combining Model-Based Clinical Trial Simulation, Pharmacoeconomics, and Value of Information to Optimize Trial Design.

The Bayesian decision-analytic approach to trial design uses prior distributions for treatment effects, updated with likelihoods for proposed trial data. Prior distributions for treatment effects based on previous trial results risks sample selection bias and difficulties when a proposed trial differs in terms of patient characteristics, medication adherence, or treatment doses and regimens. The aim of this study was to demonstrate the utility of using pharmacometric-based clinical trial simulation (CTS) to generate prior distributions for use in Bayesian decision-theoretic trial design. The methods consisted of four principal stages: a CTS to predict the distribution of treatment response for a range of trial designs; Bayesian updating for a proposed sample size; a pharmacoeconomic model to represent the perspective of a reimbursement authority in which price is contingent on trial outcome; and a model of the pharmaceutical company return on investment linking drug prices to sales revenue. We used a case study of febuxostat versus allopurinol for the treatment of hyperuricemia in patients with gout. Trial design scenarios studied included alternative treatment doses, inclusion criteria, input uncertainty, and sample size. Optimal trial sample sizes varied depending on the uncertainty of model inputs, trial inclusion criteria, and treatment doses. This interdisciplinary framework for trial design and sample size calculation may have value in supporting decisions during later phases of drug development and in identifying costly sources of uncertainty, and thus inform future research and development strategies.

Second-line treatment with lesinurad and allopurinol versus febuxostat for management of hyperuricemia: a cost-effectiveness analysis for Spanish patients.

INTRODUCTION/OBJECTIVES: Lesinurad, in combination with allopurinol, has been approved for treatment of patients with gout which do not reach therapeutic serum urate target with xanthine oxidase inhibitors monotherapy. The study aimed to assess the incremental cost-effectiveness ratio of adding lesinurad to allopurinol as second-line therapy, compared to febuxostat for patients with gout in Spain. METHOD: A Markov model representing disease evolution was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-year (QALY). Patients could either continue with second-line treatment with lesinurad (200 mg/daily) plus allopurinol (400 mg/daily) or febuxostat (80 mg/daily) switch to allopurinol monotherapy (271 mg/daily) in case of intolerance or discontinue treatment. The treatment's efficacy captured in the transition probabilities between health states were derived from CLEAR and EXCEL trials. Quality of life related to gout severity and flare frequency was considered by means of utilities. The total cost estimation (€, 2019) included drug acquisition cost, disease monitoring, and flare management cost. Unitary local costs derived from databases and literature. A 3% annual discount rate was applied for cost and outcomes. RESULTS: Lesinurad plus allopurinol provided higher QALYs (14.79) than febuxostat (14.69). Total accrued cost/patient was lower with lesinurad and allopurinol (€50,631.51) versus febuxostat (€56,698.64). Lesinurad plus allopurinol resulted more effective and less costly (dominant option) versus febuxostat. CONCLUSIONS: Lesinurad plus allopurinol therapy compared with febuxostat seems an effective option for the management of hyperuricemia in patients who did not reach serum urate target to previous allopurinol monotherapy, associated to cost-savings for the Spanish Health System.Key Points• Lesinurad, in combination with allopurinol, has been recently authorized as second-line treatment of hyperuricemia in gout patients.• Lesinurad plus allopurinol provided higher effectiveness in terms of quality-adjusted-life-years (14.79) than febuxostat (14.69).• Lesinurad plus allopurinol resulted less costly (total cost/per patient) compared with febuxostat.• Lesinurad plus allopurinol resulted a dominant option compared with febuxostat.

Cost-Effectiveness Analysis of Lesinurad/Allopurinol Versus Febuxostat for the Management of Gout/Hyperuricemia in Italy.

BACKGROUND: Until very recently the only therapeutic alternative for the management of patients affected by gout/hyperuricemia that did not respond to a first-line treatment based on allopurinol alone or who cannot tolerate allopurinol was febuxostat, a xanthine oxidase non-purine-selective inhibitor. Lately, however, a new therapeutic alternative has become available for the management of this pathology: lesinurad, a urate transporter inhibitor. OBJECTIVE: To objective of this study was to evaluate the cost effectiveness of lesinurad/allopurinol in comparison with febuxostat as a second-line therapeutic strategy for the management of patients affected by gout and hyperuricemia that did not respond to a first-line therapy based on allopurinol alone. METHODS: A Markov model was built based on the natural history of the pathology; patients entered the model according to their level of serum uric acid concentration and flowed across it according to their response to the therapy. The analysis was carried out considering the perspective of the Italian National Health Service on a lifetime horizon and 6-month cycles. Costs and quality-adjusted life-years (QALYs) were discounted at a 3.5% yearly rate. The results of the model were expressed in terms of incremental cost-effectiveness ratio (ICER). Both a one-way and a multi-way Monte-Carlo analysis were carried out in order to check the robustness of the results achieved. RESULTS: The ICER derived from the comparison was equal to €77.53/QALY on the lifetime horizon, as there was a higher level of costs associated with the combination as compared with febuxostat (€10,658.27 vs. €10,645.87, for a differential of €12.40) and a higher level of QALYs achieved (7.77 vs. 7.61, for a differential of 0.16). CONCLUSIONS: The lesinurad/allopurinol combination is recommended for the treatment of patients affected by gout/hyperuricemia in the Italian Health System as it appears to be cost effective and thus sustainable for the Italian healthcare sector.

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.

Hyperuricemia is associated with increased hospitalization risk and healthcare costs: Evidence from an administrative database in Italy.

BACKGROUND AND AIM: Chronic hyperuricemia is responsible for a relevant burden of articular diseases and cardio-nephrometabolic disorders. We evaluated the effect of high serum uric acid (SUA) levels on hospitalization risk and mortality and on healthcare costs in a real-life setting. METHODS AND RESULTS: We conducted a retrospective analysis using a large administrative database and a clinical registry among 112,170 subjects from three Italian local health units. Individuals were divided into four groups according to their SUA levels: <6 mg/dL (66.5%), >6 mg/dL and ≤7 mg/dL (19.3%), >7 mg/dL and ≤8 mg/dL (8.7%), and >8 mg/dL (5.5%). Compared to those with SUA level of <6 mg/dL, the risk of hospitalization related to gout and/or nephrolithiasis was higher in the three groups of patients with higher SUA levels (1.51, P = 0.100; 2.21, P = 0.005; and 1.17, P = 0.703, respectively). A similar trend was also observed for hospitalization due to chronic kidney disease (CKD) (1.31, P < 0.001; 1.40, P < 0.001; and 2.18, P < 0.001, respectively) and cardiovascular disease (CVD) (1.08, P < 0.001; 1.23, P < 0.001; and 1.67, P < 0.001, respectively) and for all-cause mortality (0.97, P = 0.309; 1.21, P < 0.001; and 2.15, P < 0.001). The mean annual healthcare costs were higher in patients with higher SUA level (€2752, €2957, €3386, and €4607, respectively) mainly because of a progressive increase in hospitalization costs per patient (from € 1515 for SUA <6 mg/dL to € 3096 for SUA >8 mg/dL). CONCLUSIONS: Increased SUA levels are associated with an increased risk of hospitalizations related to hyperuricemia, CKD, and CVDs and total mortality, and consequently with higher total healthcare costs and hospitalization costs per patient.

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.

A new perspective on the pharmacoeconomics of colchicine.

BACKGROUND: Gout is a common inflammatory arthritis that affects ∼4% of the US population. Most patients with gout are >50 years of age and have multiple comorbidities. Gout is caused by the deposition of monosodium urate crystals in joints secondary to hyperuricemia. Gout typically presents as an acute painful inflammation (flare) involving one or more joint. Left untreated it can progress into a more chronic polyarthritis. Acute gout flare treatment options include colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), and corticosteroids. The safety and efficacy of colchicine, especially in the presence of comorbidity and potential contraindications, has only recently been systematically investigated. METHODS: Through the use of a systematic computer-based literature analysis, this pharmacoeconomic review evaluated costs, risks, and benefits of Colcrys (colchicine) compared with other treatments for gout in the US. RESULTS: Both colchicine and NSAIDs are historically associated with gastrointestinal (GI) adverse events (AEs). Colchicine has very low risk for AEs, even in patients with GI disorders; whereas, NSAIDS are contraindicated in patients with GI disorders, renal insufficiency, and heart failure. The monthly cost of treating 100 patients with Colcrys was $33,100 compared with $3000 for NSAIDs. However, hospitalization for GI complications (1.8%) and heart failure (1.9%) is common with NSAIDs and can increase the monthly cost of treating 100 patients with NSAIDs to $161,000, considering $15,000-20,000 per day of hospitalization. CONCLUSIONS: Considering high costs associated with treating patients with gout, it seems prudent to choose the treatment with greatest benefit, lowest cost, and least risk. Despite higher cost per dose, colchicine appears to be more cost effective for management of gout flares than NSAIDs.

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.

Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of febuxostat for the management of hyperuricaemia in patients with gout based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two randomised controlled trials comparing the efficacy and safety of febuxostat with allopurinol. The trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. A pooled clinical efficacy analysis showed that a daily dose of 80 mg or 120 mg of febuxostat was significantly more effective than fixed-dose allopurinol (300/100 mg/day) at lowering serum uric acid (sUA) levels to therapeutic targets (< 6 mg/dl); however, a large percentage of febuxostat patients did not achieve the primary end point and the fixed-dose allopurinol regimen may have introduced bias. There were no differences between treatments in more clinically important outcomes such as gout flares and tophi resolution after 52 weeks of treatment. No subgroup analyses were conducted for patients with renal impairment, non-responders to allopurinol or patients with severe disease. Supplementary data from a 2-year open-label extension study were also provided, but were difficult to interpret and poorly reported. The incidence of adverse events was similar between treatments, although more febuxostat recipients discontinued treatment prematurely. A decision tree model was developed to determine the cost-effectiveness of febuxostat. The scope was limited to the comparison of continual febuxostat treatment with continual allopurinol treatment. Switching between treatments or withdrawing treatment in patients whose sUA levels had not decreased was not permitted. The model predicted a cost-effectiveness of 16,324 pounds [95% confidence interval (CI) 6281 pounds to 239,928 pounds] per quality-adjusted life-year (QALY) gained for febuxostat compared with allopurinol after 2 years of treatment. The incremental cost per QALY was below 20,000 pounds in 63% of the simulations undertaken. Changes in the time horizon did not materially affect the results. The ERG believes that the modelling structure employed was not appropriate to estimate the cost-effectiveness of febuxostat within a treatment algorithm. In addition, there were concerns about the methodology used for collecting data on key model inputs. Given these reservations the cost-effectiveness of febuxostat could not be determined. The guidance issued by NICE in August 2008 as a result of the STA states that febuxostat is recommended as an option for the management of chronic hyperuricaemia in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated.

Frequency, risk, and cost of gout-related episodes among the elderly: does serum uric acid level matter?

OBJECTIVE: We examined the association between serum uric acid (SUA) level and the frequency, risk, and cost of gout flares among the elderly. METHODS: Data were extracted from the Integrated Healthcare Information Services claims database (1999-2005). Patients were included if they had gout, were aged 65 years and older and had both medical and pharmacy benefits, and electronic laboratory data. Patients with gout and gouty episodes were identified using algorithms based on ICD-9-CM codes and medications. Logistic regression and negative binomial regressions were used to study the relationship between SUA concentration and the annual frequency and one-year risk of gout episodes. Generalized linear models were used to examine the direct healthcare costs associated with gout episodes in the 30 days following each episode. RESULTS: Elderly patients with gout (n = 2237) with high (6-8.99 mg/dl) and very high (> 9 mg/dl) SUA concentrations were more likely to develop a flare within 12 months compared to patients with normal (< 6 mg/dl) SUA levels (OR 2.1, 95% CI 1.7-2.6; OR 3.4, 95% CI 2.6-4.4, respectively). In multivariate regressions, the average annual number of flares increased by 11.9% (p < 0.001) with each unit-increase in SUA level above 6 mg/dl (p < 0.001). Among patients with very high SUA levels, average adjusted total healthcare and gout-related costs per episode were $2,555 and $356 higher, respectively, than those of patients with normal SUA levels (both p < 0.001). CONCLUSION: Higher SUA levels are associated with increased frequency and risk of gout episode, and with higher total and gout-related direct healthcare costs per episode.

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.

A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout.

Allopurinol, the first-line drug for serum urate-lowering therapy in gout, is approved by the US Food and Drug Administration for a dose up to 800 mg/d and is available as a low-cost generic drug. However, the vast majority of allopurinol prescriptions are for doses < or = 300 mg/d, which often fails to adequately treat hyperuricemia in gout. This situation has been promoted by longstanding, non-evidence-based guidelines for allopurinol use calibrated to renal function (and oxypurinol levels) and designed, without proof of efficacy, to avoid allopurinol hypersensitivity syndrome. Severe allopurinol hypersensitivity reactions are not necessarily dose-dependent and do not always correlate with serum oxypurinol levels. Limiting allopurinol dosing to < or = 300 mg/d suboptimally controls hyperuricemia and fails to adequately prevent hypersensitivity reactions. However, the long-term safety of elevating allopurinol dosages in chronic kidney disease requires further study. The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.

The effect of serum urate on gout flares and their associated costs: an administrative claims analysis.

BACKGROUND: Increased serum urate (sUA) levels (> or =6.0 mg/dL) are associated with increased likelihood of acute gout attacks, or "flares." OBJECTIVES: Identify gout flares with administrative claims data; examine the relationship between sUA and flares; examine the association between sUA and flare-related costs. METHODS: This retrospective administrative claims analysis examined subjects with gout (> or =2 medical claims with ICD-9-CM diagnosis code 274.xx or > or =1 claim with a gout diagnosis and > or =1 pharmacy claim for allopurinol, probenecid, colchicine, or sulfinpyrazone) between January 1, 2002 and March 31, 2004. Each subject was observed during 1-year baseline and 1-year follow-up periods. Gout flares were identified with an algorithm using claims for services associated with flares. Outcomes were sUA (mg/dL) and flare-related health care costs. Logistic regression examined the likelihood of flare; generalized linear modeling regression measured the impact of baseline sUA on flare costs, controlling for demographic and health status variables. RESULTS: The study sample comprised 18,243 subjects with mean age of 53.9 years. sUA was available for 4277 (23%) subjects. Sixty-two percent (11,253) of subjects had > or =1 flare. The number of mean, unadjusted flares increased with sUA. Logistic results showed subjects with baseline sUA > or =6.0 relative to sUA <6.0 had 1.3 times the odds of gout flare (P <0.05). Generalized linear modeling results showed that baseline sUA > or =6.0 was associated with 2.1 to 2.2 times higher flare costs than was baseline sUA <6.0 (P <0.05). CONCLUSIONS: sUA was a significant predictor both of gout flare and related costs. This highlights the importance of gout management strategies aimed at controlling sUA.

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.

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.