Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States.

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Budget Impact of Oral Semaglutide Intensification versus Sitagliptin among US Patients with Type 2 Diabetes Mellitus Uncontrolled with Metformin.

BACKGROUND: Oral semaglutide was approved in 2019 for blood glucose control in patients with type 2 diabetes mellitus (T2DM) and was the first oral glucagon-like peptide 1 receptor agonist (GLP-1 RA). T2DM is associated with substantial healthcare expenditures in the US, so the cost of a new intervention should be weighed against clinical benefits. OBJECTIVE: This study evaluated the budget impact of a treatment pathway with oral semaglutide 14 mg daily versus oral sitagliptin 100 mg daily among patients not achieving target glycated hemoglobin (HbA1c) level despite treatment with metformin. METHODS: This study used the validated IQVIA™ CORE Diabetes Model to simulate the treatment impact of oral semaglutide 14 mg and sitagliptin 100 mg over a 5-year time horizon from a US healthcare sector (payer) perspective. Trial data (PIONEER 3) informed cohort characteristics and treatment effects, and literature sources informed event costs. Population and market share data were from the literature and data on file. The analysis evaluated the estimated budget impact of oral semaglutide 14 mg use for patients currently using sitagliptin 100 mg considering both direct medical and treatment costs to understand the impact on total cost of care, given underlying treatment performance and impact on avoidable events. RESULTS: In a hypothetical plan of 1 million lives, an estimated 1993 patients were treated with sitagliptin 100 mg in the target population. Following these patients over 5 years, the incremental direct medical and treatment costs of a patient using oral semaglutide 14 mg versus sitagliptin 100 mg was $US16,562, a 70.7% increase (year 2019 values). A hypothetical payer would spend an additional $US3,300,143 (7.1%) over 5 years for every 10% of market share that oral semaglutide 14 mg takes away from sitagliptin 100 mg. Univariate and scenario analyses with alternate inputs and assumptions demonstrated consistent results. CONCLUSIONS: Use of oral semaglutide 14 mg in patients currently receiving sitagliptin 100 mg substantially increases the budget impact for patients with T2DM whose blood glucose level is not controlled with metformin over a 5-year time horizon for US healthcare payers.

Patients with type 2 diabetes mellitus (T2DM) have many treatment options. Choices depend on factors such as cost, preference, and patient characteristics. Oral semaglutide was recently approved for the treatment of T2DM as the first oral therapy of its class. This study estimated the cost for patients treated with sitagliptin 100 mg, a commonly used T2DM treatment, versus oral semaglutide 14 mg for patients whose disease is not well controlled with metformin. Costs and effects were estimated over 5 years for each treatment strategy using predictive model equations and clinical trial data for the two treatments. These costs were considered for both a hypothetical healthcare plan of 1 million lives and the full US population. A patient treated with oral semaglutide 14 mg would expect to see 70.7% higher costs than a patient treated with sitagliptin 100 mg over 5 years. For every 10% of patients who would switch from sitagliptin 100 mg to oral semaglutide 14 mg, costs would increase by 7.1%. Changing the cost of oral semaglutide 14 mg had the greatest impact on model results. The findings from the analysis were consistent across a range of alternate model inputs. Oral semaglutide 14 mg is more costly than sitagliptin 100 mg over 5 years.

A Budget Impact and Cost Per Additional Responder Analysis for Baricitinib for the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients with an Inadequate Response to Tumor Necrosis Factor Inhibitors in the USA.

BACKGROUND/OBJECTIVE: Baricitinib is a selective and reversible Janus kinase (JAK) inhibitor indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor inhibitors (TNFis) and has been shown to improve multiple clinical and patient-reported outcomes. However, it is unclear what the budgetary impact would be for US commercial payers to add baricitinib to their formulary and how the efficacy of baricitinib compares to other disease-modifying antirheumatic drugs (DMARDs) with a similar indication. METHODS: A budget impact model (BIM) was developed for a hypothetical population of 1 million plan members that compared a world without and with baricitinib. A retrospective observational study was carried out to estimate market utilization of advanced therapies. Number needed to treat (NNT) and cost per additional responder were calculated for American College of Rheumatology (ACR) 20%/50%/70% improvement criteria (ACR20/50/70) response outcomes combining cost estimates from the BIM and efficacy values from a network meta-analysis (NMA). The model included costs related to drug acquisition and monitoring costs. RESULTS: Adding baricitinib would save a commercial payer $US169,742 for second-line therapy and $US135,471 for third-line therapy over a 2-year time horizon (all costs correspond to 2019 US dollars). Cost savings were driven by baricitinib drawing market share away from more expensive comparators. The NMA, based on nine studies, found no statistically significant differences in the median treatment difference between baricitinib and comparators except for versus a conventional synthetic DMARD (csDMARD), and thus NNT versus a csDMARD was similar. The cost per additional responder for baricitinib in patients with inadequate response to a TNFi was substantially lower than all other treatments for all three ACR response criteria at 12 weeks (ACR20: $US129,672; ACR50: $US237,732; ACR70: $US475,464), and among the lowest at 24 weeks (ACR20: $US167,811; ACR50: $US259,344; ACR70: $US570,557). CONCLUSIONS: Baricitinib, compared to other DMARDs, was a less expensive option (- $US0.01 incremental cost per member per month in second- and third-line therapy over a 2-year time horizon) with comparable efficacy in patients with inadequate response to TNFi. Adding baricitinib to formulary would likely be cost saving for US payers and expands treatment options for these patients.

Correction to: A Budget Impact and Cost Per Additional Responder Analysis for Baricitinib for the Treatment of Moderate-to-Severe Rheumatoid Arthritis in Patients with an Inadequate Response to Tumor Necrosis Factor Inhibitors in the USA.

Due to a single error in the annual cost of sarilumab the following needs to be corrected in the article.

The Cost-effectiveness of a Flash Glucose Monitoring System for Management of Patients with Type 2 Diabetes Receiving Intensive Insulin Treatment in Sweden.

Flash glucose monitoring, an alternative to traditional self-monitoring of blood glucose (SMBG), prevents hypoglycaemic events without impacting glycated haemoglobin (REPLACE trial). Given the potential benefits, this study assessed the cost-effectiveness of using flash monitoring versus SMBG alone in patients with type 2 diabetes (T2D) receiving intensive insulin treatment in Sweden.Methods: This study used the IQVIA CORE Diabetes Model (IQVIA CDM, v8.5) to simulate the impact of flash monitoring versus SMBG over 40 years from the Swedish societal perspective. Baseline characteristics, intervention effects, and resource utilisation were derived from REPLACE; literature and Tandvårds-Läkemedelförmånsverket (TLV) sources informed utilities and costs. Scenario analyses explored the effect of key base case assumptions. Results: In base case analysis, direct medical costs for flash monitoring use were SEK1,630,586 (€158,523) versus SEK1,459,394 (€141,902) for SMBG use. Flash monitoring led to 0.56 additional quality-adjusted life years (QALYs; 6.21 versus 5.65 SMBG) for an incremental cost-effectiveness ratio (ICER) of SEK306,082/QALY (€29,762/QALY). ICERs for all scenarios remained under SEK400,000/QALY (€38,894/QALY). Conclusions: Hypoglycaemia and health utility benefits due to flash glucose monitoring may translate into economic value compared to SMBG. With robust results across scenario analyses, flash monitoring may be considered cost-effective in a Swedish population of T2D intensive insulin users.

Angioedema Among Hypertensive Patients Treated with Aliskiren or Other Antihypertensive Medications in the United States.

BACKGROUND: A non-interventional study suggested that use of angiotensin-converting enzyme inhibitors (ACEIs) or aliskiren was associated with an angioedema risk three times that of beta-blockers (BBs). OBJECTIVE: The aim was to assess angioedema incidence rates (IRs) and the relative angioedema risk of aliskiren compared to other antihypertensive drugs (AHDs). METHODS: A cohort study in hypertensive patients with an AHD prescription between 2007 and 2012 was conducted using data from the US PharMetrics Plus™ claims database. Angioedema was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) code 995.1. Additionally, a nested case-control analysis was conducted to assess the relative angioedema risk of aliskiren or other AHDs versus BBs. RESULTS: A total of 3,090,114 patients were included (aliskiren n = 30,720). There were 15,744 angioedema events (IR 2.28/1000 person-years; 95% confidence interval (CI) 2.24-2.32). Aliskiren IRs were: any aliskiren 2.58 (2.08-3.17), aliskiren monotherapy 1.71 (0.74-3.37), aliskiren fixed-dose combination (FDC) 1.27 (0.41-2.96), and aliskiren free-standing combination (FSC) 2.93 (2.31-3.66). The case-control analysis included 15,100 angioedema cases and 60,400 controls; the angioedema risk for both aliskiren monotherapy and FDC was not significantly different from BBs [adjusted odds ratio (adjOR) 0.99 (95% CI 0.45-2.20) and 1.06 (0.40-2.76)]; aliskiren FSC was associated with an increased angioedema risk [adjOR 3.29 (2.42-4.48)], mainly driven by concomitant ACEI use [adjOR 7.03 (4.10-12.05)]. CONCLUSIONS: The IR and risk of angioedema in patients with aliskiren monotherapy or FDC are comparable to BBs. The higher IR and risk of angioedema identified in the aliskiren FSC group may largely be driven by the concomitant use of ACEIs.

Economic burden of toxicities associated with treating metastatic melanoma in eight countries.

BACKGROUND: Information on costs of managing adverse events (AEs) associated with current treatments in metastatic melanoma is limited. This study estimates costs of AEs in eight countries: Australia (AU), Canada (CA), France (FR), Germany (GE), Italy (IT), the Netherlands (NL), Spain (ES), and the UK. METHODS: A literature search was conducted to identify grade 3/4 AEs from product label, published trials, conference abstracts, and treatment guidelines. Resource utilization for the management of each type of AE was determined via interviews with 5 melanoma clinicians in each country. Outpatient and inpatient costs were estimated for each type of AE using country-specific tariffs or government/published sources. RESULTS: In outpatient settings, the most costly AEs per incident included cutaneous squamous cell carcinoma (CSCC) (€1063, £720; NL/UK), anemia (€1443, €1329, €1285; ES/IT/FR), peripheral neuropathy (€1289; ES), and immune-related diarrhea (AUS$1,121; AU). In inpatient settings, the most costly AEs per hospitalization included hypophysitis (€10,265; €5316; CAN$9735; AUS$7231: ES/FR/CA/AU), dyspnea (€9077; GE), elevated liver enzymes (€6913, CAN$8030, AUS$6594; FR/CA/AU), CSCC (CAN$8934; CA), peripheral neuropathy (€6977, €4144, CAN$9472; NL/ES/CA), and diarrhea (£4284, €4113; UK/ES). CONCLUSIONS: Costs of managing AEs can be significant, and thus effective treatments with lower rates of severe AEs would be valuable.

Economic Burden of Toxicities Associated with Treating Metastatic Melanoma in the United States.

BACKGROUND: Little has been reported on the costs of managing the adverse events (AEs) associated with current therapies for patients with regional or distant metastatic melanoma. OBJECTIVES: To identify treatment-related AEs in patients with metastatic melanoma and to estimate the associated costs of treating these AEs in the United States. METHODS: A cost-estimation study for AEs associated with treatment of metastatic melanoma was conducted from 2012 to 2013 by identifying grades 3 and 4 AEs through the use of a comprehensive search of drug labels and English-language, published phase 2/3 studies in PubMed, conference abstracts, and the National Comprehensive Cancer Network guidelines. Resource utilization for the management of each type of AE in the outpatient setting was obtained via interviews with 5 melanoma specialists in the United States. Unit costs for an AE associated with melanoma treatment in the outpatient setting were assigned using Medicare reimbursement rates to obtain these costs. Hospitalization and length-of-stay costs were estimated for each associated AE using the large national claims database Optum Clinformatics Data Mart for the period of July 1, 2004, to November 30, 2012. RESULTS: The most common AEs associated with chemotherapies used for melanoma were neutropenia, vomiting, and anemia. The most common AEs associated with vemurafenib were cutaneous squamous-cell carcinoma or keratoacanthoma, rash, and elevated liver enzymes; the most common AEs associated with dabrafenib were cutaneous squamous-cell carcinoma and pyrexia. Trametinib was most often associated with hypertension and rash. The most common AEs with ipilimumab were immune-related diarrhea or colitis, dyspnea, anemia, vomiting, and, less frequently, hypophysitis. The most common grade 3/4 AE with talimogene laherparepvec was cellulitis. The highest treatment costs for an AE in the outpatient setting were for neutropenia ($2092), headache ($609), and peripheral neuropathy ($539). The highest mean inpatient costs for an AE were for acute myocardial infarction, sepsis, and coma, which ranged from $31,682 to $47,069. Colitis or diarrhea, cutaneous squamous-cell carcinoma, thrombocytopenia, hyponatremia, oliguria or anuria, hypertension, anemia, and elevated liver enzymes were associated with mean costs for hospitalization ranging from $19,122 to $26,861. CONCLUSION: The costs of managing treatment-related AEs in patients with metastatic melanoma are substantial. Effective treatments with improved safety profiles may help to reduce these costs. Until real-world evidence for the costs associated with treatment toxicity is available in the outpatient and inpatient settings, the costs estimated in this study can help inform decision makers about the cost-effectiveness of managing patients with metastatic melanoma.