An updated cost-effectiveness analysis of axicabtagene ciloleucel in second-line large B-cell lymphoma patients in the United States.

AIMS: This economic evaluation of axicabtagene ciloleucel (axi-cel) versus previous standard of care (SOC; salvage chemotherapy followed by high-dose therapy with autologous stem cell rescue) in the second line (2L) large B-cell lymphoma population is an update of previous economic models that contained immature survival data. METHODS: This analysis is based on primary overall survival (OS) ZUMA-7 clinical trial data (median follow-up of 47.2 months), from a United States (US) payer perspective, with a model time horizon of 50 years. Mixture cure models were used to extrapolate updated survival data; subsequent treatment data and costs were updated. Patients who remained in the event-free survival state by 5 years were assumed to have achieved long-term remission and not require subsequent treatment. RESULTS: Substantial survival and quality of life benefits were observed despite 57% of patients in the SOC arm receiving subsequent cellular therapy: median model-projected (ZUMA-7 trial Kaplan-Meier estimated) OS was 78 months (median not reached) for axi-cel versus 25 months (31 months) for SOC, resulting in incremental quality-adjusted life year (QALY) difference of 1.63 in favor of axi-cel. Incrementally higher subsequent treatment costs were observed in the SOC arm due to substantial crossover to cellular therapies, thus, when considering the generally accepted willingness to pay threshold of $150,000 per QALY in the US, axi-cel was cost-effective with an incremental cost-effectiveness ratio of $98,040 per QALY. CONCLUSIONS: Results remained consistent across a wide range of sensitivity and scenario analysis, including a crossover adjusted analysis, suggesting that the mature OS data has significantly reduced the uncertainty of axi-cel's cost-effectiveness in the 2L setting in the US. Deferring treatment with CAR T therapies after attempting a path to transplant may result in excess mortality, lower quality of life and would be an inefficient use of resources relative to 2L axi-cel.

The Efficiency of Increased HCV Testing and Treatment Strategies in Spain to Achieve Elimination Goals.

BACKGROUND: In 2015, Spain launched a national eradication strategy for hepatitis C virus (HCV), resulting in the highest treatment rate in Europe and substantial reductions in HCV prevalence. However, to achieve the goal of HCV elimination, it is necessary to scale-up the diagnosis, treatment, and management of HCV infection. OBJECTIVE: Our aim was to assess the prevalence, incidence, and cost effectiveness of scaling-up compared with status quo scenarios. METHODS: A compartmental dynamic transmission model was developed comprising of a cascade of care and a liver progression module. Cost and quality-of-life inputs were sourced from the literature. Key outcomes were the prevalence and incidence of HCV and the incremental cost per quality-adjusted life-year (QALY) and per life-year (LY). Outcomes for a hypothetical elimination strategy were compared with the status quo. RESULTS: The base-case analysis found that scaling-up testing and treatment reduced both the prevalence and incidence of HCV over time, resulting in incremental costs per QALY and LY of €13,291 and €12,285 respectively, compared with the status quo. The main drivers of the cost-effectiveness results included cost of diagnosis, cost of treatment, proportion of people who are unaware, percentage of population who inject drugs, and calibration parameters related to HCV infection prevalence. CONCLUSIONS: This analysis demonstrated that scaling-up testing and treatment with direct-acting antivirals may be an efficient strategy for reducing the incidence and prevalence of HCV and may help achieve HCV elimination goals in Spain.

Budget impact analysis of transurethral water vapor therapy for treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia in the Spanish national healthcare system.

BACKGROUND: Several surgical treatments are available for managing lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH). Water vapor thermal therapy (WVTT) is a new minimally invasive therapy. This study estimates the budget impact of introducing WVTT for LUTS/BPH into the Spanish health care system. METHODS: A model simulated the evolution of men over 45 years of age with moderate-severe LUTS/BPH after surgical treatment, over a 4-year time horizon, from the Spanish public health care service´s perspective. The technologies in scope included those most used in Spain: WVTT, transurethral resection (TURP), photoselective laser vapourization (PVP) and holmium laser enucleation (HoLEP). Transition probabilities, adverse events and costs were identified from the scientific literature and validated by a panel of experts. Sensitivity analyses were performed by varying the most uncertain parameters. RESULTS: Per intervention, WVTT resulted in savings of €3,317, €1,933 and €2,661 compared to TURP, PVP and HoLEP. Over a 4-year time horizon, when performed in 10% of the cohort of 109,603 Spanish males with LUTS/BPH, WVTT saved €28,770,125 against the scenario without WVTT availability. CONCLUSIONS: WVTT could reduce the cost of managing LUTS/BPH, increase the quality of health care and reduce the length of procedure and hospital stay.

The Cost-Effectiveness of Axicabtagene Ciloleucel as Second-Line Therapy in Patients with Large B-Cell Lymphoma in the United States: An Economic Evaluation of the ZUMA-7 Trial.

Axicabtagene ciloleucel (axi-cel) was found to have superior clinical outcomes compared to standard of care (SOC; salvage chemoimmunotherapy, followed by high-dose therapy with autologous stem cell rescue for responders) for second-line large B-cell lymphoma (2L LBCL) in the pivotal ZUMA-7 trial. The aim of this analysis was to evaluate the cost effectiveness of using axi-cel compared to the current standard 2L LBCL therapy. A 3-state partitioned-survival model estimated the cost effectiveness and budget impact from a payer perspective in the United States. Clinical outcomes were extrapolated based on the pivotal trial. The model calculated expected quality-adjusted life years (QALYs), total costs (in United States dollars [USD], and the incremental cost-effectiveness ratio (ICER), along with the budget impact. Sensitivity and scenario analyses were performed. The proportion alive at 10 years was estimated as 48% for axi-cel and 38% for SOC; median overall survival was estimated at 59 and 24 months for axi-cel and SOC, respectively. Over a lifetime horizon, the model estimated a total of 5.56 and 7.08 QALYs for SOC and axi-cel, respectively, of which 41% and 74% were in the event-free state, respectively. Incremental QALYs and costs were 1.51 and $100,366 USD, resulting in an ICER of $66,381 USD per QALY for axi-cel versus SOC. Despite crossover to subsequent CAR T in the SOC arm, second-line CAR T use was found to improve the quality and length of life compared to SOC. Cost offsets due to subsequent CAR T use led to a limited incremental cost difference. Treatment with axi-cel is a cost-effective option that addresses an important unmet clinical need for patients with LBCL who relapse or are refractory to front-line therapy.

Breathing Synchronised Hypoglossal Nerve Stimulation with Inspire for Untreated Severe Obstructive Sleep Apnoea/Hypopnoea Syndrome: A Simulated Cost-Utility Analysis from a National Health Service Perspective.

BACKGROUND: Hypoglossal nerve stimulation (HNS) with Inspire is a novel treatment indicated for moderate or severe obstructive sleep apnoea/hypopnoea syndrome (OSAHS), intolerant to or unable to be treated with continuous positive airway pressure (CPAP). OBJECTIVE: The aim of this study was to assess the cost effectiveness of treating moderate or severe OSAHS, in patients intolerant to CPAP, with HNS, compared with standard care, from a National Health Service (NHS) perspective. METHODS: A cohort state transition model was developed to compare HNS with Inspire with no treatment in UK adult patients with moderate or severe OSAHS who have previously tried and have not responded to CPAP therapy. Published literature was applied in the model to estimate incremental cost-effectiveness ratios (ICERs; 2019 Great British pounds per quality-adjusted life-year [QALY] gained), from an NHS and personal social services (PSS) perspective, over a cohort's lifetime. RESULTS: The model base-case predicts that patients undergoing HNS will incur lifetime costs of £65,026 compared with £36,727 among untreated patients. The HNS cohort would gain 12.72 QALYs compared with 11.15 QALYs in the no-treatment arm. The ICER of treating severe OSAHS with HNS is therefore estimated to be £17,989 per QALYs gained. Probabilistic sensitivity analysis found that at a threshold of £30,000/QALY, HNS has a 69% probability of being cost effective. Limitations of the model include uncertainty around the utility data that were not sourced directly from HNS clinical trials. There is further uncertainty in the relationship between change in the Apnoea-Hypopnoea Index (AHI) and reduction in ischaemic heart disease and stroke because of difficulty capturing the reduction in risk over a long time horizon in studies. CONCLUSIONS: Over a patient's lifetime, HNS with Inspire is expected to be cost effective when compared with no treatment in patients with severe OSAHS who have tried and have not responded to CPAP, from an NHS perspective.

Minimally Invasive Sacroiliac Joint Fusion with Triangular Titanium Implants: Cost-Utility Analysis from NHS Perspective.

OBJECTIVE: The aim was to identify the cost-effectiveness of minimally invasive sacroiliac joint fusion (MI SIJF) surgery with titanium triangular implants for patients with sacroiliac joint (SIJ) pain who have failed conservative management, compared to non-surgical management (NSM) from a National Health Service (NHS) England perspective. METHODS: Over a time horizon of 5 years, a cohort state transition model compared the costs and outcomes of treating patients with MI SIJF to those of traditional NSM treatment pathways. The NSM arm included two treatments: grouped physical therapy and corticosteroid injections (PTSI) or radiofrequency ablation (RFA). Three different strategies were considered: (1) a stepped pathway, (2) patients split between PTSI and RFA, and (3) RFA only. The outcome measure was incremental cost-effectiveness ratio (ICER), reported in 2018 British pounds per quality-adjusted life year (QALY) gained. One-way and probabilistic sensitivity analyses were used to test the robustness of the model results. RESULTS: Patients undergoing MI SIJF accrued total procedure-related and pain-management costs of £8358, while NSM treatment strategy 1 had total costs of £6880. The MI SIJF cohort had 2.98 QALYs compared to strategy 1 with 2.30 QALYs. This resulted in an ICER for MI SIJF versus strategy 1 of £2164/QALY gained. Strategy 2 of the NSM arm had lower costs than strategy 1 (£6564) and 2.26 QALYs, and this resulted in an ICER of £2468/QALY gained for MI SIJF. Strategy 3 of the NSM arm had lower costs than strategy 1 (£6580), and this resulted in 2.28 QALYs and an ICER of £2518/QALY gained for MI SIJF. Probabilistic sensitivity analysis shows that at a threshold of £20,000/QALY gained, MI SIJF has a probability of being cost-effective versus NSM strategies of 96%, 97%, and 91% for strategies 1, 2, and 3, respectively. CONCLUSION: MI SIJF appears to be cost-effective over a 5-year time horizon when compared to traditional NSM pathways in an NHS context.

Clinical and economic benefits of a new paradigm of HCV diagnosis and treatment.

Introduction: The current paradigm (CP) of hepatitis C virus (HCV) diagnosis and treatment in Italy's National Health Service system has numerous steps. The European Association for the Study of the Liver recommends initiation of a pan-genotypic direct-acting antiviral regimen after a simple diagnostic process. The present study estimated the efficiency gains resulting from two simplified pathways from diagnosis to treatment of chronic hepatitis C patients in Italy over the next 5 years from a societal perspective. Methods: The CP, a New Paradigm 1 (NP1), and a New Paradigm 2 (NP2) were evaluated in a Markov model. The NP1 model simplifies monitoring and laboratory test requirements in the diagnosis and treatment phases. The NP2 model also eliminates the primary care referral requirement. Results: Treatment process time for non-cirrhotic patients was 48, 43, and 25 weeks in the CP, NP1, and NP2, respectively, and in cirrhotic patients was 49, 46, and 37 weeks. Under the CP, 19% of patients/year would be lost to follow-up, which decreases by 11% in NP1 and 100% in NP2. Compared with the CP, implementation of NP1 at 5 years would reduce compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and liver-related deaths by 12.6%, 12.4%, 8.1%, and 8.8%, respectively; these cases would be reduced by 94.0%, 93.8%, 61.0%, and 58.4% in NP2. Total 5-year costs with the CP, NP1, and NP2 are estimated at 135.6€ million, 110.5€ million, and 80.5€ million, respectively. Conclusions: Simplification of HCV diagnosis and monitoring requirements would allow Italy to move closer to international guidelines with significant health benefits and economic gains.

Cost-effectiveness of increased screening and treatment of chronic hepatitis C in Korea.

Background: Given a hepatitis C virus (HCV) elimination goal by 2030, World Health Organization (WHO) guidelines recommend scaling up HCV screening and treatment with highly-effective direct-acting antivirals (DAAs). This study investigated the cost-effectiveness of various screening and treatment strategies for chronic HCV patients in South Korea in patients aged over 40 as compared to currently screening only high-risk patients.Methods: A published Markov disease progression model was used with a screening/treatment decision-tree to model different screening and treatment strategies for Korean HCV patients (aged over 40) from a national payer perspective over a lifetime time horizon. The screening strategies included "screen-all" (upfront only: "once"; or upfront and age 65: "twice") or a "high-risk only" screening strategy followed by treatment. Treatment strategies included either ledipasvir/sofosbuvir (LDV/SOF), SOF + ribavirin (SOF + RBV; in GT2 only), or glecaprevir/pibrentasvir (GLE/PIB). Model inputs were sourced from published literature and costing databases and validated by Korean hepatologists.Results: Regardless of treatment strategy, a "screen all twice" scenario led to the lowest rates of advanced liver disease events compared to "screen all once" and "high-risk only" screening scenarios. In this screening scenario, treatment with LDV/SOF for GT1/2 dominates (i.e. is more effective and less4costly) LDV/SOF in GT1 and SOF + RBV in GT2, while GLE/PIB is not cost-effective relative to LDV/SOF (₩105,124,920/QALY) at a willingness-to-pay threshold of 1xGDP per capita.Conclusion: Screening all South Korean patients twice followed by LDV/SOF treatment is cost-effective as compared current high-risk screening. Adopting this strategy can help achieve WHO HCV elimination goals.

In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered.

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment with all oral direct acting antiviral agents (DAA's) achieve sustained virologic response (SVR) rates of 98%. Re-assessment of general US population screening for HCV is imperative. This study compared the cost-effectiveness (CE) of three HCV screening strategies: screen all (SA), screen Birth Cohort (BCS), and screen high risks (HRS). METHODS: Using a previous designed decision-analytic Markov model, estimations of the natural history of HCV and CE evaluation of the three HCV screening strategies over a lifetime horizon in the US population was undertaken. Based on age and risk status, 16 cohorts were modelled. Health states included: Fibrosis stages 0 to 4, decompensated cirrhosis, hepatocellular carcinoma, LT, post-LT, and death. The probability of liver disease progression was based on the presence or absence of virus. Treatment was with approved all-oral DAAs; 86% were assumed to be seen annually by a primary care provider; SVR rates, transition probabilities, utilities, and costs were from the literature. One-way sensitivity analyses tested the impact of key model drivers. RESULTS: SA cost $272.0 billion [$135 279 per patient] and led to 12.19 QALYs per patient. BCS and HRS cost $274.5 billion ($136 568 per patient) and $284.5 billion ($141 502 per patient) with 11.65 and 11.25 QALYs per patient respectively. Compared to BCS, SA led to an additional 0.54 QALYs per patient and saved $2.59 billion; compared to HRS, SA led to 0.95 additional QALYs per patient and saved $12.5 billion. CONCLUSIONS: Screening the entire US population and treating active viraemia was projected as cost-saving.