Population Health Model Predicting the Long-Term Impact of Sotatercept on Morbidity and Mortality in Patients with Pulmonary Arterial Hypertension (PAH).

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT. BGT was comprised of mono-, double-, or triple-PAH targeted therapy. Building on STELLAR findings, we employed a population health model to assess the potential long-term clinical impact of sotatercept. METHODS: Based on the well-established ESC/ERS 4-strata risk assessment approach, we developed a six-state Markov-type model (low risk, intermediate-low risk, intermediate-high risk, high risk, lung/heart-lung transplant, and death) to compare the clinical outcomes of sotatercept plus BGT versus BGT alone over a lifetime horizon. State-transition probabilities were obtained from STELLAR. Risk stratum-adjusted mortality and lung/heart-lung transplant probabilities were based on COMPERA PAH registry data, and the post-transplant mortality probability was obtained from existing literature. Model outcomes were discounted at 3% annually. Sensitivity analyses were conducted to examine model robustness. RESULTS: In the base case, sotatercept plus BGT was associated with longer life expectancy from model baseline (16.5 vs 5.1 years) versus BGT alone, leading to 11.5 years gained per patient. Compared with BGT alone, sotatercept plus BGT was further associated with a gain in infused prostacyclin-free life years per patient, along with 683 PAH hospitalizations and 4 lung/heart-lung transplant avoided per 1000 patients. CONCLUSIONS: According to this model, adding sotatercept to BGT increased life expectancy by roughly threefold among patients with PAH while reducing utilization of infused prostacyclin, PAH hospitalizations, and lung/heart-lung transplants. Real-world data are needed to confirm these findings. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04576988 (STELLAR).

Cost-effectiveness of axicabtagene ciloleucel versus lisocabtagene maraleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the US.

AIMS: This study evaluated from a US payer perspective the cost-effectiveness of two chimeric antigen receptor T (CAR T) cell therapies, axicabtagene ciloleucel (axi-cel) versus lisocabtagene maraleucel (liso-cel), for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following two or more systemic therapy lines. METHODS: We developed a 3-state (i.e., pre-progression, post-progression, death) partitioned survival model to estimate patients' lifetime outcomes. Mixture cure models were used for survival extrapolation to account for long-term remission. Survival inputs were based on a matching-adjusted indirect comparison (MAIC) that reweighted the ZUMA-1 population (receiving axi-cel) to match patient characteristics in TRANSCEND-NHL-001 (assessing liso-cel). Costs included apheresis, drug acquisition, and administration for conditioning chemotherapy and CAR T therapies, monitoring, transplant, hospitalization, adverse events, routine care, and terminal care, per published literature and databases. Utilities were derived from ZUMA-1 and literature. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: In the base case, axi-cel was associated with more QALYs (7.76 vs. 5.94) and greater costs overall ($611,440 vs. $597,174) than liso-cel, at $7,843/QALY gained. The incremental costs (+$14,266) were largely driven by higher routine care costs (+$18,596) due to longer survival and hospitalization (+$10,993) but partially offset by reduced costs of CAR T acquisition (‒$11,300) and terminal care (‒$4,025). Sensitivity analyses consistently suggested robustness of base-case results. LIMITATIONS: This study relied on an MAIC in which trial design differences and unobserved confounders could not be accounted for. Future real-world studies for recently approved CAR T are warranted to validate our results. Due to a lack of data, we assumed equivalent use of transplants and treatment for B-cell aplasia between the two therapies based on clinicians' opinions. CONCLUSIONS: In the US, axi-cel is a potentially cost-effective treatment option compared with liso-cel for adult patients with r/r LBCL after two or more systemic therapy lines.

Real-world cost-effectiveness of primary prophylaxis with G-CSF biosimilars in patients at intermediate/high risk of febrile neutropenia.

Background: Real-world data suggests superiority of pegfilgrastim (PEG) over filgrastim (FIL) in reducing the incidence of chemotherapy-induced febrile neutropenia (FN), probably attributable to underdosed FIL in practice. We used real-world data to assess the cost-effectiveness of primary prophylaxis with PEG versus FIL in cancer patients at intermediate-to-high risk of FN from a US payer perspective. Methods: A Markov model with lifetime horizon. Results: For the high-risk group, PEG (vs FIL) biosimilars resulted in 0.43 FN events prevented (FNp), 0.27 quality-adjusted life-years gained (QALYg) and a cost saving of USD$5703. For the intermediate-risk group, PEG biosimilar led to 0.18 FNp and 0.12 QALYg, at USD$9674/FNp and USD$14,502/QALYg. Conclusion: PEG biosimilars may provide opportunities to optimize FN management in patients with intermediate-to-high FN risk.

Our results have demonstrated that, by taking the real-world dosing and effectiveness of pegfilgrastim versus filgrastim into account, pegfilgrastim biosimilars have the potential to financially optimize neutropenia management in cancer patients by reducing febrile neutropenia (FN) incidence and FN-related healthcare resource utilization, and to potentially improve health outcomes. Extending primary prophylaxis with pegfilgrastim biosimilars from cancer patients with high-to-intermediate risk of FN resulted in clinical benefits, at acceptable incremental costs. Given the accelerated availability of pegfilgrastim biosimilars, it is important to instigate a rethink of FN management in cancer patients and implement guidelines that maximize the benefits of pegfilgrastim both clinically and economically.

Cost Effectiveness of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Heart Failure Event from a US Medicare Perspective.

OBJECTIVE: Given the high economic burden of disease among adult patients with chronic heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event in the US, this study aimed to estimate the cost effectiveness of vericiguat plus prior standard-of-care therapies (PSoCT) versus PSoCT alone from a US Medicare perspective. METHODS: A four-state Markov model (alive prior to heart failure hospitalization, alive during heart failure hospitalization, alive post-heart failure hospitalization, and death) was developed to predict clinical and economic outcomes, based on the results of the VICTORIA trial, in which patients with chronic HFrEF following a worsening heart failure were randomized to placebo or vericiguat, in addition to PSoCT, which consisted of ß-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan. Risks of heart failure hospitalization and cardiovascular mortality were based on multivariable regression models derived from VICTORIA data. Utilities were derived from VICTORIA EQ-5D data and the literature. Costs included drug acquisition, heart failure hospitalization, routine care, and terminal care. Primary outcomes included heart failure hospitalization, cardiovascular mortality, life-years, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a 30-year lifetime horizon, discounted at 3.0% annually. RESULTS: For the VICTORIA overall intent-to-treat population, compared with PSoCT, vericiguat plus PSoCT resulted in 19 fewer heart failure hospitalizations and 13 fewer cardiovascular deaths per 1000 patients, as well as 0.28 QALY gained per patient at an incremental cost of $23,322, leading to $82,448 per QALY gained. CONCLUSIONS: Based on the results of VICTORIA, patients treated with vericiguat had lower rates of heart failure hospitalization and cardiovascular death. The addition of vericiguat to PSoCT was estimated to increase QALYs and to be cost effective at a willingness-to-pay threshold of $100,000 per QALY gained.

Budget Impact Analysis of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Event.

INTRODUCTION: In the USA, patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) following a worsening HF event (WHFE) have significantly increased healthcare resource use and medical costs. This analysis aimed to estimate the budget impact of vericiguat as an add-on therapy to guideline-directed medical therapy (GDMT) for the treatment of chronic HFrEF following a WHFE from a US commercial payer perspective. METHODS: A model was developed to estimate the budget impact of adding vericiguat to the formulary by comparing a current scenario (GDMT) and a new scenario (vericiguat plus GDMT) to a hypothetical 10-million-member commercial payer over a 3-year time horizon. Epidemiology data was obtained from literature. Treatment utilization rates of GDMT and clinical inputs (HF hospitalization and cardiovascular [CV] morality) were based on the VICTORIA trial in which patients with chronic HFrEF following a WHFE were randomized to GDMT plus placebo or GDMT plus vericiguat. Costs (2020 US$) included drug acquisition, hospitalization, routine care, and mortality. RESULTS: Approximately 20,510 prevalent cases in year 1 and 3109 annual incident cases in subsequent years were estimated to be eligible for treatment with vericiguat. At a utilization rate of 5%, 10%, and 15% for vericiguat over years 1-3, the per member per month (PMPM) budget impact was estimated to be $0.048, $0.064, and $0.086, respectively, associated with 44, 32, and 30 fewer HF hospitalizations and 7, 12, and 18 fewer CV deaths, respectively. Reduction in HF hospitalizations and CV deaths reduced the budget impact by 14% in total over 3 years. CONCLUSION: Adding vericiguat to commercial plan formulary was associated with limited budget impact, primarily driven by drug acquisition costs but partially offset by reduced cost of HF hospitalizations and CV deaths.

Biosimilar pegfilgrastim may offer affordable treatment options for patients in France: a budget impact analysis on the basis of clinical trial and real-world data.

BACKGROUND: NYVEPRIA, a pegfilgrastim (a long-acting granulocyte colony-stimulating factor [G-CSF]) biosimilar, was recently recommended for marketing authorization in Europe for decreasing the incidence of febrile neutropenia (FN) in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs. The present study aimed to evaluate the financial impact of introducing a new pegfilgrastim biosimilar from a French healthcare system perspective. METHODS: An Excel-based budget impact model was developed to estimate the financial impact by introducing a new pegfilgrastim biosimilar (NYVEPRIA) to France over a 5-year time horizon. Comparators included existing long-acting and short-acting G-CSFs. The burden of FN was obtained from existing literature. Costs (2021 Euros) included drug acquisition and administration, estimated based on drug dosage in both clinical trial and real-world settings. Scenario analyses were conducted to examine the robustness of key model assumptions. RESULTS: In a total French population of 67.19 million, 79,873 patients were estimated to be treated with G-CSFs annually. The annual number of patients to be treated with NYVEPRIA was estimated to be 1593, 3195, 3674, 3782, and 4052 in years 1 to 5, respectively. Using real-world data, NYVEPRIA resulted in total annual cost savings of €8,620, €868,498, €868,498, €814,102, and €958,952 over years 1 to 5, respectively, leading to a cumulative 5-year cost savings of €3,518,669. Using data from clinical trials, NYVEPRIA resulted in total annual cost savings of €14,366, €1,447,496, €1,447,496, €1,356,836, and €1,598,253 over years 1 to 5, respectively, leading to a cumulative 5-year cost savings of €5,864,448. CONCLUSIONS: The introduction of a new pegfilgrastim biosimilar (NYVEPRIA) is potentially associated with substantial cost savings for the French healthcare system.

Cost effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the United States.

AIMS: To assess from a US payer perspective the cost-effectiveness of the chimeric antigen receptor T (CAR T)-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) to treat relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following ≥2 systemic therapy lines. METHODS: A three-state (i.e. pre-progression, post-progression, and death) partitioned survival model was used to estimate the quality-adjusted life-years (QALYs) and costs for patients on each treatment over a lifetime horizon. Progression-free survival (PFS) and overall survival (OS) were based on a matching-adjusted indirect treatment comparison (MAIC) that accounted for differences in trial population baseline characteristics. Mixture cure models (MCMs) were used to account for long-term survivors. Costs included drug acquisition and administration for the CAR T-cell therapies and conditioning chemotherapy, apheresis, CAR T-specific monitoring, transplant, hospitalization, adverse events, routine care, and terminal care. Health state utilities were derived from trial and published data. Sensitivity analyses included probabilistic sensitivity analyses (PSAs) and an analysis of extremes that assessed the results across a vast array of combinations of parametric OS and PFS curves across the two therapies. RESULTS: Compared to tisa-cel, axi-cel resulted in 2.31 QALYs gained and a cost reduction of $1,407 in the base case. In the PSA, the cost per QALY gained was ≤$31,500 in 95% of the 1,000 simulations. In the analysis of extremes, the cost per QALY gained was ≤$7,500 in 99% of the 1,296 combinations of MCMs and ≤$40,000 in 95% of the 1,296 combinations of standard models. LIMITATIONS: In absence of head-to-head comparative data, we relied on a MAIC, which cannot account for all possible confounders. Moreover, some outcomes (i.e. transplantations, hospitalizations, adverse events (AEs)) were not adjusted in the MAIC. CONCLUSIONS: In this simulation, axi-cel was a superior treatment option as it is predicted to achieve better outcomes at lower or minimal incremental costs versus tisa-cel.

Does Biosimilar Bevacizumab Offer Affordable Treatment Options for Cancer Patients in the USA? A Budget Impact Analysis from US Commercial and Medicare Payer Perspectives.

BACKGROUND: Bevacizumab remains the most widely used and most thoroughly characterized angiogenesis inhibitor for a range of advanced cancers. Bevacizumab-bvzr (Zirabev®), a biosimilar of bevacizumab, was recently approved by the US Food and Drug Administration (FDA), which provides a less costly option. This study aimed to evaluate the financial impact of introducing bevacizumab-bvzr from US commercial and Medicare payer perspectives. METHODS: A Microsoft Excel-based budget impact model was developed over a 5-year time horizon. Target population was patients to be treated with bevacizumab for FDA-approved indications. Drug costs (2020 US$) were based on average sales price and wholesale acquisition cost, accounting for payer-specific reimbursement models and provider settings. Drug dosing and duration were based on prescribing information and pivotal trial publications. RESULTS: In a hypothetical 10-million-member health plan, 503 and 723 patients were estimated to be treated with bevacizumab in year 1 and year 5, respectively. Assuming an annual market shift of 1.7%, 3.6%, 6.7%, 9.4%, and 11.9% to bevacizumab-bvzr, an annual cost saving of $313,363 ($0.003 per member per month [PMPM]) was estimated for a commercial payer and $92,880 ($0.001 PMPM) for Medicare in year 1. Cumulative 5-year cost savings were $7,030,924 ($0.012 PMPM) for a commercial payer and $4,059,257 ($0.007 PMPM) for Medicare. More than half of the cost savings was attributed to patients with metastatic colorectal cancer. CONCLUSIONS: The introduction of biosimilar bevacizumab-bvzr was estimated to provide substantial cost savings for US payers, which would allow additional patients access to bevacizumab treatment.

Early Exposure to Cumulative Social Risk and Trajectories of Body Mass Index in Childhood.

BACKGROUND: Childhood social risk has been associated with increased risk of childhood obesity. However, little is known about early exposure of cumulative social risk on BMI percentile (BMIp) trajectories in early childhood. METHODS: Public data from the Fragile Families and Child Wellbeing Study were analyzed (N = 3809). Maternal reports of experiences of multiple social risk factors were obtained at age 1 and 3 assessments of children. Two cumulative social risk scores were calculated by summing social factors assessed at age 1 and at age 3. Child BMIp was assessed at ages 3, 5, and 9. Linear mixed models were used to examine the effect of cumulative social risk on sex-specific BMIp trajectories. RESULTS: Compared with girls experiencing low social risk at either age 1 or 3, girls experiencing high social risk (≥ 2 factors) at age 1 or 3 only had higher initial BMIp at age 3 [ß0 = 5.70 (95% confidence interval, CI: 0.15-1.26) and 1.37 (95% CI: -2.25 to 4.99), respectively] and had nonsignificantly greater BMIp growth rate [ß1 = 0.39 (95% CI: -0.86 to 1.63) and 0.32 (95% CI: -0.86 to 1.63)]. Girls experiencing high social risk at both ages had nonsignificantly but consistently lower BMIp [ß1 = -1.24 (95% CI: -2.93 to 0.46)]. In addition, girls experiencing a sum of ≥4 risk factors at both ages had lower BMIp growth rate [ß1 = -1.77 (95% CI: -3.39 to -0.15)] compared to girls experiencing no risk factor. No associations were observed among boys. CONCLUSIONS: Early exposure to cumulative social risk may have long-term impact on BMIp trajectories among girls, depending on timing of exposure. Understanding the effect of cumulative social risk in different contexts, including sex, chronicity, and timing of exposure, may have practical implications for informing effective intervention to combat childhood obesity.