Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.

OBJECTIVES: To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective. METHODS: A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed. RESULTS: The ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen. CONCLUSION: Allopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.

Cost-Effectiveness of Colchicine Prophylaxis for Gout Flares When Commencing Allopurinol.

OBJECTIVE: Colchicine prophylaxis to prevent gout flares when commencing urate-lowering therapy is recommended by international rheumatology society guidelines. Whether this is a cost-effective intervention is currently unknown. Our objective was to perform a cost-effectiveness analysis using both a US cost input model and an Australian cost input model. METHODS: This cost-effectiveness analysis was completed from the point of view of the third-party payer. We used a 2-arm decision tree with 1 arm commencing allopurinol with no colchicine prophylaxis and the other with colchicine prophylaxis. Model inputs were drawn from published literature where available. We completed a univariate and probabilistic sensitivity analysis to confirm the robust nature of the modeling. The time frame for the model was 6 months. RESULTS: The colchicine prophylaxis arm resulted in a cost of $1,276 and 0.49 quality-adjusted life-years (QALYs), while in the placebo arm the cost was $516 and 0.47 QALYs, with an incremental cost-effectiveness ratio of $34,004 per QALY gained. In Australia, where cost of colchicine was much lower, the colchicine arm dominated the placebo ($208 [Australian] in the colchicine arm versus $415 [Australian] in the placebo). Univariate and probability sensitivity analysis demonstrated that results were robust to changes in input parameters. In the probabilistic sensitivity analysis, the probability of colchicine prophylaxis being the most cost-effective option was 93% in the US and 100% in the Australian setting. CONCLUSION: Colchicine prophylaxis to prevent gout flares while commencing allopurinol in gout is very cost-effective.

Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore.

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.Results: Sequential treatment of allopurinol 300 mg/day-allopurinol 600 mg/day-probenecid ("standard of care") was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.

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 rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China.

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.

Integration of Pharmacometrics and Pharmacoeconomics to Quantify the Value of Improved Forgiveness to Nonadherence: A Case Study of Novel Xanthine Oxidase Inhibitors for Gout.

Linked pharmacometric and pharmacoeconomic models provide a structured approach for assessing the value of candidate drugs in development. The aim of this study was to assess the utility of such an approach for identifying the properties of xanthine oxidase inhibitors (XOi) providing improved forgiveness to nonadherence and estimate the maximum reimbursement price. The pharmacometric and pharmacoeconomic models were used to simulate the time course of serum uric acid concentrations and estimate quality-adjusted life years and costs for the XOi febuxostat and a range of hypothetical analogues. Compounds with reduced clearance or increased potency were more forgiving to missed doses, however, even following relatively large changes in these properties the predicted maximum reimbursement prices represented an increase of only 19% above febuxostat 80 mg. Linked pharmacometric and pharmacoeconomic modeling methods have the potential to inform early drug development by providing an indication of pricing options that may permit reimbursement.

Cost-Effectiveness of Panel Tests for Multiple Pharmacogenes Associated With Adverse Drug Reactions: An Evaluation Framework.

The cost-effectiveness of testing for multiple genes implicated in adverse drug reactions requires the simultaneous assessment of all actionable information, including future prescribing decisions based on incidental findings. We developed methodology for determining the value of pharmacogenetic panel tests, illustrated with a multigene panel, including HLA-A*31:01, HLA-B*15:02, HLA-B*57:01, HLA-B*58:01, HLA-B (158T), and HLA-DQB1 (126Q). If the findings for all alleles are acted upon, regardless of their individual cost-effectiveness, the HLA panel resulted in cost savings of £378 (US $491), and a quality-adjusted life year gain of 0.0069. Based on a stratified analysis and compared with no testing, initial use of the panel was cost-effective in patients eligible for abacavir (HLA-B*57:01), carbamazepine (HLA-A*31:01), and clozapine (HLA-B (158T) and HLA-DQB1 (126Q)), but not for carbamazepine (HLA-B*15:02) or allopurinol (HLA-B*58:01). The methods presented allow for the assessment of the cost-effectiveness of multiple-gene panels.

Cost-effectiveness of an adherence-enhancing intervention for gout based on real-world data.

AIM: Medication non-adherence influences outcomes of therapies for chronic diseases. Allopurinol is a cornerstone therapy for patients with gout; however, non-adherence to allopurinol is prevalent in Singapore and limits its effectiveness. Between 2008-2010, an adherence-enhancing program was implemented at the rheumatology division of a public tertiary hospital. The cost-effectiveness of this program has not been fully evaluated. With healthcare resources being finite, the value of investing in adherence-enhancing interventions should be ascertained. This study aims to evaluate the cost-effectiveness of this adherence-enhancing program to inform optimal resource allocation toward better gout management. METHOD: Adopting a real-world data approach, we utilized patient clinical and financial records generated in their course of routine care. Intervention and control groups were identified in a standing database and matched on nine risk factors through propensity score matching. Cost and effect data were followed through 1-2 years. A decision tree was developed in TreeAge using a societal perspective. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty. RESULTS: At an assumed willingness-to-pay threshold of $50 000 USD ($70 000 SGD) per quality-adjusted life year (QALY), the intervention had an 85% probability of being cost-effective compared to routine care. The incremental cost-effectiveness ratio was $12 866 USD per QALY for the base case and ranged from $4 139 to $21 593 USD per QALY in sensitivity analyses. CONCLUSION: The intervention is cost-effective in the short-term, although its long-term cost-effectiveness remains to be evaluated.

Impact of Non-Adherence and Flare Resolution on the Cost-Effectiveness of Treatments for Gout: Application of a Linked Pharmacometric/Pharmacoeconomic Model.

BACKGROUND: Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses. OBJECTIVES: To estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY). METHODS: Treatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model. RESULTS: The base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence. CONCLUSIONS: The estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

Comparison of fixed versus traditional weight-based dosing of rasburicase in a pediatric population.

BACKGROUND: The American Society of Clinical Oncology guidelines recommend rasburicase for the treatment of pediatric patients with hyperuricemia at risk of tumor lysis syndrome (TLS) using a weight-based dose of 0.1-0.2 mg/kg once daily for 1-7 days. However, there has been a trend in practice due to recent data showing benefit using a fixed-dose approach. The purpose of this study was to evaluate the efficacy and safety between fixed and weight-based dosing of rasburicase in a pediatric population. PROCEDURE: This was a retrospective chart review of 48 patients from January 1, 2007 to August 31, 2016 at Children's National Health System. Patients less than 18 years old with a documented diagnosis of a malignancy and baseline uric acid level were included; patients less than 30 kg at the time of rasburicase administration were excluded. RESULTS: The primary endpoint of this study was the treatment success of normalization of uric acid level (<5 mg/dl) within 24 hr of rasburicase administration. Eighty-three percent of patients had success with normalization of uric acid post rasburicase dose. Eighty-five percent of patients had success in the weight-based group compared to eighty-one percent in the fixed-dose group (P = 0.715). Mean percent reduction of uric acid at 24 hr was relatively similar between both groups (94% vs. 89%). CONCLUSION: Our results suggest that a fixed-dose strategy of rasburicase is both safe and effective in reducing uric acid levels in the pediatric patient population. A fixed dose of rasburicase 6 mg is a cost-effective treatment option for TLS.

Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective.

Aim: To estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years.

A retrospective investigation of HLA-B*5801 in hyperuricemia patients in a Han population of China.

BACKGROUND: Hyperuricemia and gout have become increasingly prevalent in China. Allopurinol is an effective urate-lowering therapy, but it has severe side effects. HLA-B*5801 is highly associated with the allopurinol-induced toxic epidermal necrolysis and Stevens-Johnson syndrome. PATIENTS AND METHODS: In this retrospective report, we had genotyped HLA-B*5801 in 253 cases of hyperuricemia and gout patients in a Han population in Shenzhen and analyzed the clinical management of medications. RESULTS: We found 30 carriers of the HLA-B*5801 allele in 253 cases of hyperuricemia or gout patients in the population (11.9%). Allopurinol was prescribed in both HLA-B*5801-positive and HLA-B*5801-negative groups. The evaluation of four models with or without genetic screening and management of allopurinol or febuxostat indicated that the HLA-B*5801 screening had significant cost benefit for clinical management. CONCLUSION: For appropriate management and cost-effectiveness, the HLA-B*5801 allele should be screened in all patients with hyperuricemia and gout in the Chinese population.

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.

Cost Comparison of Urate-Lowering Therapies in Patients with Gout and Moderate-to-Severe Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) are at increased risk for developing gout and having refractory disease. Gout flare prevention relies heavily on urate-lowering therapies such as allopurinol and febuxostat, but clinical decision making in patients with moderate-to-severe CKD is complicated by significant comorbidity and the scarcity of real-world cost-effectiveness studies. OBJECTIVE: To compare total and disease-specific health care expenditures by line of therapy in allopurinol and febuxostat initiators after diagnosis with gout and moderate-to-severe CKD. METHODS: A retrospective observational cohort study was conducted to compare mean monthly health care cost (in 2012 U.S. dollars) among gout patients with CKD (stage 3 or 4) who initiated allopurinol or febuxostat. The primary outcome was total mean monthly health care expenditures, and the secondary outcome was disease-specific (gout, diabetes, renal, and cardiovascular disease [CVD]) expenditures. Gout patients (ICD-9-CM 274.xx) aged ≥ 18 years with concurrent CKD (stage 3 or 4) were selected from the MarketScan databases (January 2009-June 2012) upon allopurinol or febuxostat initiation. Patients were followed until disenrollment, discontinuation of the qualifying study agent, or use of the alternate study agent. Patients initiating allopurinol were subsequently propensity score-matched (1:1) to patients initiating febuxostat. Five generalized linear models (GLMs) were developed, each controlling for propensity score, to identify the incremental costs (vs. allopurinol) associated with febuxostat initiation in first-line (without prior allopurinol exposure) and second-line (with prior allopurinol exposure) settings. RESULTS: Propensity score matching yielded 2 cohorts, each with 1,486 patients (64.6% male, mean [SD] age 67.4 [12.8] years). Post-match, 74.6% of patients had stage 3 CKD; 82.9% had CVD; and 42.1% had diabetes. The post-match sample was well balanced on numerous comorbidities and medication exposures with the following exception: 50.0% of febuxostat initiators were treated in the second-line setting; that is, they had baseline exposure to allopurinol, whereas only 4.2% of allopurinol initiators had baseline exposure to febuxostat. Unadjusted mean monthly cost was $1,490 allopurinol and $1,525 febuxostat (P = 0.809). GLM results suggest that first-line febuxostat users incurred significantly (P = 0.009) lower cost than allopurinol users ($1,299 vs. $1,487), whereas second-line febuxostat initiators incurred significantly (P = 0.001) higher cost ($1,751 vs. $1,487). Febuxostat initiators in both settings had significantly (P < 0.001) higher gout-specific cost, due to higher febuxostat acquisition cost. Increased gout-specific cost in the first-line febuxostat cohort was offset by significantly (P < 0.001) lower CVD ($288 vs. $459) and renal-related cost ($86 vs. $216). There were no significant differences in either renal or CVD costs (adjusted) between allopurinol initiators treated almost exclusively in the first-line setting and second-line febuxostat patients. CONCLUSIONS: Gout patients with concurrent CKD, initiating treatment with febuxostat in a first-line setting, incurred significantly less total cost than patients initiating allopurinol during the first exposure to each agent. Conversely, patients treated with second-line febuxostat following allopurinol incurred significantly higher total cost than patients initiating allopurinol. There was no significant difference in total cost between the agents across line of therapy. Although study findings suggest the potential for CVD and renal-related savings to offset febuxostat's higher acquisition cost in gout patients with moderate-to-severe CKD, this is the first such retrospective evaluation. Future research is warranted to both demonstrate the durability of study findings and to better elucidate the mechanism by which associated cost offsets occur. DISCLOSURES: No outside funding supported this study. Turpin is an employee of Takeda Pharmaceuticals U.S.A. Mitri and Wittbrodt were employees of Takeda Pharmaceuticals U.S.A. at the time of this study. Tidwell and Schulman are employees of Outcomes Research Solutions, consultants to Takeda Pharmaceuticals U.S.A. All authors contributed to the design of the study and to the writing and review of the manuscript. All authors read and approved the final manuscript. Tidwell and Schulman collected the data, and all authors participated in data interpretation.

Cost-effectiveness analysis of febuxostat in patients with gout in Spain.

UNLABELLED: Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout. Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80 mg and 120 mg sequentially, used as first line and second line therapy, was compared with allopurinol 300 mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6 mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied. PERSPECTIVE: National Health System. Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300 mg ranging from €5268-€9737. Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000€/QALY).

Febuxostat in the management of gout: a cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout. METHODS: A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40-80 mg and allopurinol 100-300 mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided. RESULTS: Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures. CONCLUSIONS: Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.

Cost-effectiveness analysis of genotyping for HLA-B*5801 and an enhanced safety program in gout patients starting allopurinol in Singapore.

AIMS: Allopurinol is an efficacious urate-lowering therapy (ULT), but is associated with rare serious adverse drug reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with higher risk among HLA-B*5801 carriers. We assessed the cost-effectiveness of HLA-B*5801 testing, an enhanced safety program or strategies with both components. METHODS: The analysis adopted a health systems perspective and considered Singaporean patients with chronic gout, over a lifetime horizon, using allopurinol or probenecid. The model incorporated SJS/TEN and gout treatment outcomes, allele frequencies, drug prices and other medical costs. RESULTS: Based on cost-effectiveness threshold of US$50,000 per quality-adjusted life year, HLA-B*5801-guided ULT selection or enhanced safety program was not cost effective. Avoidance of ULTs was the least preferred strategy as uncontrolled gout leads to lower quality-adjusted life years and higher costs. CONCLUSION: The analysis underscores the need for biomarkers with higher positive predictive value for SJS/TEN, less expensive genetic tests or safety programs, or more effective gout drugs. .

Reductions in Use of Colchicine after FDA Enforcement of Market Exclusivity in a Commercially Insured Population.

BACKGROUND: A brand-name version of colchicine (Colcrys) was introduced after its manufacturer conducted a clinical trial in acute gout patients, leading to higher prices for this drug. OBJECTIVE: We analyzed the impact of the new single-source colchicine product on prescribing and patient health spending as well as incidence rates of potentially dangerous concomitant use of clarithromycin and cyclosporine after formal FDA approval. DESIGN/PARTICIPANTS: We conducted a retrospective cohort study of UnitedHealth-affiliated enrollees newly diagnosed with gout or FMF. MAIN MEASURES: Among gout and FMF patients separately, we assessed linear trends in colchicine prescriptions, prescription drug costs, and total health care costs from 2009 to September 2010 (market exclusivity announced) compared to January 2011 (market exclusivity enforced) through 2012. Next, we estimated trends in co-prescription within 15 days of clarithromycin, azithromycin (indicated on the Colcrys label for use in place of clarithromycin), and cyclosporine. KEY RESULTS: Among gout patients, before Colcrys' market exclusivity, the odds of receiving colchicine within 30 days of gout diagnosis increased 1.4 %/month (OR: 1.014, 95 % CI: 1.011-1.018). Following FDA action, the odds decreased by 0.5 %/month (OR: 0.995, 95 % CI: 0.992-0.999) (p < 0.001). Similarly, among FMF patients, odds of initiating colchicine changed from an increase of 2.8 %/month to a decrease by 7.6 %/month (p = 0.01). Patients receiving colchicine experienced increases in average monthly prescription drug costs ($418 vs. $651, p < 0.001) and health care costs ($3,406 vs. $3,534, p < 0.001). Incidence rates of colchicine/clarithromycin co-prescription before and after FDA action did not change, while co-prescription of colchicine/cyclosporine increased after introduction of Colcrys [-0.75 monthly change in patients (95 % CI: -1.07, -0.43) vs. 0.13 (95 % CI: -0.16, 0.42), p < 0.001]. CONCLUSIONS: The FDA's actions were associated with a reduction in colchicine initiation and an increase in patient spending. By contrast, we did not observe any association with improvements in avoidance of potentially dangerous co-prescriptions.