Economic evaluation of betibeglogene autotemcel (Beti-cel) gene addition therapy in transfusion-dependent ß-thalassemia.

Background: Standard of care (SoC) for transfusion-dependent ß-thalassemia (TDT) requires lifelong, regular blood transfusions as well as chelation to reduce iron accumulation. Objective: This study investigates the cost-effectiveness of betibeglogene autotemcel ('beti-cel'; LentiGlobin for ß-thalassemia) one-time, gene addition therapy compared to lifelong SoC for TDT. Study design: Microsimulation model simulated the lifetime course of TDT based on a causal sequence in which transfusion requirements determine tissue iron levels, which in turn determine risk of iron overload complications that increase mortality. Clinical trial data informed beti-cel clinical parameters; effects of SoC on iron levels came from real-world studies; iron overload complication rates and mortality were based on published literature. Setting: USA; commercial payer perspective Participants: TDT patients age 2-50 Interventions: Beti-cel is compared to SoC. Main outcome measure: Incremental cost-effectiveness ratio (ICER) utilizing quality-adjusted life-years (QALYs) Results: The model predicts beti-cel adds 3.8 discounted life years (LYs) or 6.9 QALYs versus SoC. Discounted lifetime costs were $2.28 M for beti-cel ($572,107 if excluding beti-cel cost) and $2.04 M for SoC, with a resulting ICER of $34,833 per QALY gained. Conclusion: Beti-cel is cost-effective for TDT patients compared to SoC. This is due to longer survival and cost offset of lifelong SoC.

Cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or standard of care in patients with type 2 diabetes and established cardiovascular disease.

INTRODUCTION: Empagliflozin, a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, is approved in the USA to reduce risk of cardiovascular (CV) death in adults with type 2 diabetes mellitus (T2DM) and established CV disease, based on EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial results. Empagliflozin reduced major adverse CV event (MACE) by 14%, CV death by 38%, and hospitalization for heart failure (HHF) by 35% vs placebo, each on top of standard of care (SoC). SGLT-2 inhibitors canagliflozin and dapagliflozin have also been compared with placebo, all on top of SoC, in CV outcome trials. In the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program, canagliflozin reduced MACE by 14% and HHF by 33%. Dapagliflozin reduced HHF by 27% in the DECLARE-TIMI 58 trial (Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events). This analysis estimated the cost-effectiveness of empagliflozin versus canagliflozin, dapagliflozin, or SoC, in US adults with T2DM and established CV disease. RESEARCH DESIGN AND METHODS: Individual patient-level discrete-event simulation was conducted to predict time-to-event for CV and renal outcomes, and specific adverse events over patients' lifetimes. Occurrence of events in EMPA-REG OUTCOME was estimated based on event-free survival curves with time-dependent covariates. An HR for canagliflozin or dapagliflozin versus empagliflozin on each clinical event was estimated from published CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME data using indirect treatment comparison. Public sources provided US costs and utilities. RESULTS: The model predicted longer survival for empagliflozin versus canagliflozin, dapagliflozin, and SoC mainly due to direct reduction in CV death. Empagliflozin dominated canagliflozin, yielding more quality-adjusted life years (QALYs; 0.38) at a lower cost (-US$306). Compared with dapagliflozin and SoC, empagliflozin yielded 0.50 and 0.84 incremental QALYs at US$1517 and US$27 539 incremental costs, yielding incremental cost-effectiveness ratios of US$3054/QALY and US$32 848/QALY, respectively. CONCLUSIONS: Empagliflozin was projected to dominate canagliflozin and be highly cost-effective compared with dapagliflozin and SoC using US healthcare costs.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.

Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making. METHODS: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC. RESULTS: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents. CONCLUSION: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

Cost-effectiveness of entecavir versus adefovir for the treatment of chronic hepatitis B in patients with decompensated cirrhosis from a third-party US payer perspective.

BACKGROUND: Decompensated cirrhosis is a serious clinical complication of chronic hepatitis B (CHB) that places a large economic burden on the US health care system. Although entecavir has been shown to improve health outcomes in a cost-effective manner in mixed populations of CHB patients, the cost-effectiveness of entecavir has not been evaluated in CHB patients with decompensated cirrhosis. METHODS: This study assessed the cost-effectiveness of entecavir versus adefovir, from a US payer perspective, in CHB patients with decompensated cirrhosis, using a health-state transition Markov model with four health states: hepatocellular carcinoma (HCC), HCC-free survival, post-liver transplant, and death. The model considered a hypothetical patient population similar to that included in a randomized controlled trial in the target population (ETV-048): predominantly male (74%), Asian (54%), mean age 52 years, hepatic decompensation (Child-Pugh score ≥ seven), hepatitis B e antigen-positive or -negative, treatment-naïve or lamivudine-experienced, and no liver transplant history. Clinical inputs were based on cumulative safety results for ETV-048 and published literature. Costs were obtained from published literature. Costs and outcomes were discounted at 3% per annum. RESULTS: For 1000 patients over a 3-year time horizon, predicted overall survival and HCC-free survival were longer with entecavir than with adefovir (2.35 versus 2.30 years and 2.11 versus 2.03 years, respectively). Predicted total health care costs were $889 lower with entecavir than with adefovir ($91,878 versus $92,768). For incremental cost/life-year gained and incremental cost/HCC-free-year gained, entecavir was less costly and more effective than adefovir. Sensitivity analyses found the results to be robust to plausible variations in health-state costs and discount rate. CONCLUSION: This analysis suggests that entecavir improves survival outcomes in a cost-saving manner compared with adefovir in CHB patients with hepatic decompensation.

Effect of a patient support program on access to oral therapy for hematologic malignancies.

PURPOSE: The results of a study assessing the effectiveness of a manufacturer-sponsored assistance program for patients prescribed oral cancer therapies are presented. METHODS: Rates of dispensing success were evaluated in a random sample of patients (n = 1000) who enrolled in the Celgene Patient Support (CPS) program for assistance obtaining lenalidomide or thalidomide over a two-year period and a control group of patients (n = 1000) who registered to receive the drugs under restricted-distribution protocols but did not receive CPS assistance. The main study outcomes were (1) the proportion of patients who actually received medication and (2) the time from prescription approval to the initial dispensing of medication. RESULTS: Despite the complex access issues faced by program enrollees, the proportion of CPS participants who received medication (89%) was comparable to the proportion of patients who received medication in the control cohort (91%). The median time from the approval of prescriptions to the initial dispensing of medication was also comparable in the CPS and control groups (eight days versus five days). The study also evaluated the reasons why medication was not dispensed to CPS enrollees in some cases. CONCLUSION: The percentage of patients who were dispensed prescriptions for lenalidomide or thalidomide did not differ significantly between those who were enrolled in a patient assistance program and those who were not. The median time between prescription authorization and first dispensing was comparable among program and nonprogram patients.

Cost-effectiveness of a fourth-generation combination immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen for the detection of HIV infections in the United States.

PURPOSE: The US Food and Drug Administration recently approved the first 4th-generation HIV test. This study evaluated the cost-effectiveness of the 4th-generation assay versus a 3rd-generation test in screening for HIV infections in the United States. METHODS: An exploratory microsimulation model was developed that follows hypothetical individuals and simulates the course of HIV/AIDS, treatment with highly active antiretroviral therapy, and transmissions. RESULTS: With a 1% HIV prevalence, screening 1.5 million individuals with the 4th- versus 3rd-generation assay resulted in detection of 266 additional HIV cases at an incremental cost per additional HIV case detected of $63,763, an additional 489 life years and 395 quality-adjusted life years (QALYs), and 26 HIV transmissions prevented. Although lifetime costs were increased by $33.6 million, the incremental cost/QALY gained was $85,206. The 4th-generation test was more cost-effective in high incidence settings. The number needed to screen to detect one additional HIV case was 5,635. CONCLUSIONS: Screening using the 4th-generation assay may be cost-effective for HIV detection in appropriate settings, resulting in increased case identification, fewer transmissions, extended life, and increased quality of life. With early and accurate detection, this 4th-generation test may provide a suitable alternative to current 3rd-generation tests.

Comparison of the metabolic and economic consequences of long-term treatment of schizophrenia using ziprasidone, olanzapine, quetiapine and risperidone in Canada: a cost-effectiveness analysis.

RATIONALE, AIMS AND OBJECTIVES: Second-generation antipsychotic agents have varying propensities to cause weight gain, elevated lipid levels and associated long-term complications. This study evaluates the cost-effectiveness of four second-generation antipsychotic agents used in Canada for the treatment of schizophrenia (ziprasidone, olanzapine, quetiapine, risperidone) with a focus on their long-term metabolic consequences. METHOD: Using data from the Clinical Antipsychotic Trials of Intervention Effectiveness Study, a semi-Markov model was developed to predict the incidence and associated costs of type 2 diabetes, cardiovascular complications (e.g. angina, myocardial infarction, stroke, cardiovascular disease death), and acute psychiatric hospitalizations in patients with chronic schizophrenia treated over 5 years. Incremental costs per quality-adjusted life year (QALY) gained were calculated from the perspective of the Canadian provincial ministries of health. Scenario and probabilistic sensitivity analyses were performed. RESULTS: The total average cost of treatment with ziprasidone was $25,301 versus $28,563 with olanzapine, $26,233 with quetiapine and $21,831 with risperidone. Ziprasidone had the lowest predicted number of type 2 diabetes cases and cardiovascular disease events, and the highest QALY gains. Patients receiving quetiapine had the highest predicted number of hospitalizations. Ziprasidone was less costly and resulted in more QALYs compared with olanzapine and quetiapine. Compared with risperidone, ziprasidone was more costly and had higher QALYs, with an incremental cost per QALY gained of $218,060. CONCLUSION: Compared with olanzapine and quetiapine, ziprasidone produced savings to the health care system. Although ziprasidone generated incremental expenditures versus risperidone, it resulted in more QALYs. Based on this analysis, ziprasidone treatment possesses cost and therapeutic advantages compared with olanzapine and quetiapine.

Economic evaluation of voriconazole for the treatment of candidemia in Canadian adults.

BACKGROUND: Candidemia is a common cause of nosocomial bloodstream infection. When selecting therapeutic treatments for candidemia, cost-effectiveness is an important consideration. The present study assessed the cost-effectiveness of voriconazole for the treatment of candidemia. METHODS: A decision-analytical model was used for evaluating the cost-effectiveness of voriconazole compared with a regimen of conventional amphotericin B (CAB) followed by fluconazole (FLU) in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting, based on the Global Candidemia Study. The time frame of the model was 98 days (14 weeks). Model parameters were based primarily on clinical outcome, and resource use data collected from the clinical trial were used. Supplemental data were obtained from an independent panel of 12 Canadian experts for parameters not available from the clinical trial. Unit costs were collected from Canadian sources. The outcome variables selected in the study were the number of patients cured within 98 days, the number of patients surviving at 98 days and the number of patients avoiding toxicity. Incremental costs per outcome were calculated to compare the cost-effectiveness analyses (both probabilistic and one-way sensitivity analyses were performed). RESULTS: The cost-effectiveness analysis demonstrated a difference of $1,121 in the total average cost of treatment with voriconazole ($70,489) versus CAB/FLU ($69,368). While the costs of voriconazole exceeded the costs of CAB/FLU, these costs were almost completely offset by lower hospitalization costs. While patients in both treatment arms experienced cure rates of 41%, both the percentage of patients surviving at day 98 (64.5% versus 58.2%) and the percentage of patients avoiding toxicity (64.5% versus 52.5%) were higher in the voriconazole arm. Accounting for differences in total costs and clinical outcomes, this analysis estimated an incremental cost per patient surviving at day 98 of $17,739, and an incremental cost per patient avoiding toxicity of $9,298. In the case of cost per patient cured, voriconazole had a higher cost ($1,121) than CAB/FLU. The results of the deterministic and probabilistic sensitivity analyses indicated that the model was robust. CONCLUSIONS: Results of the decision-analytical model provided evidence to support the cost-effectiveness of voriconazole relative to a regimen of CAB/FLU in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting.

Estimating costs of care for patients with newly diagnosed metastatic colorectal cancer.

BACKGROUND: This study examines the resource use patterns and costs of care for patients with incident metastatic colorectal cancer (mCRC) based on analyses of retrospective claims data from selected health plans in the United States. PATIENTS AND METHODS: A case-control analysis was performed using claims from years 1998-2004. Incident mCRC cases were identified based on evidence of a colorectal cancer diagnosis and a metastatic disease diagnosis. Incident mCRC cases could have no other evidence of cancer in the 1-year period before the date of their first mCRC diagnosis. Cases were matched to non-mCRC controls based on age, sex, geographic region, and duration of plan enrollment. Costs were evaluated by phase of disease: diagnosis, treatment, or death phases. Ordinary least squares regressions were performed to evaluate impact of covariates in each phase. RESULTS: Total costs in the follow-up period averaged $97,031 more for mCRC cases than for controls. The main cost drivers for mCRC were hospitalizations ($37,369) and specialist visits ($34,582), which included chemotherapy administration. Approximately 40% of the 672 patients with mCRC who qualified for the phase analysis were identified with a fatal event during follow-up. Monthly costs were similar in the diagnostic phase ($12,205) and death phase ($12,328), but were significantly lower in the treatment phase ($4722). Both mean/median monthly costs increased over time during the study period, regardless of disease phase. CONCLUSION: The economic burden of mCRC is substantial for patients with commercial health plans in the United States, and costs of care have increased substantially in recent years.