Cost-Effectiveness Analysis of Axicabtagene Ciloleucel vs. Standard of Care in Second-Line Treatment for Relapsed/Refractory Large B-Cell Lymphoma in Spain.

PURPOSE: To estimate the cost-effectiveness of axi-cel vs. salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem-cell transplantation (HDT+ASCT) for responders to second-line treatment for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). METHODS: A partitioned survival mixture-cure model comprising three health states was used to estimate the costs, life years gained (LYG), and quality-adjusted life years (QALYs) accumulated over a lifetime horizon. Overall survival, event-free survival, and time to the next treatment with axi-cel and HDT+ASCT were derived from the ZUMA-7 study. The total costs (EUR, 2022) included drug acquisition and administration, ASCT, subsequent treatment, disease and adverse event management, and palliative care. The unitary costs were derived from local databases and the literature. A 3% discount rate was applied to the costs and outcomes. RESULTS: Compared with HDT+ASCT, axi-cel provided higher LYG per patient (10.00 vs. 8.28 LYG/patient) and greater QALYs gained per patient (7.85 vs. 6.04 QALY/patient). The lifetime total costs were 343,581 EUR/patient with axi-cel vs. 257,994 EUR/patient with IQT+ASCT. The incremental cost-effectiveness ratio of axi-cel vs. HDT+ASCT was 49,627 EUR/LYG, and the incremental cost-utility ratio was 47,309 EUR/QALY. Sensitivity analyses confirmed the robustness of the model. CONCLUSION: Axi-cel is a potentially cost-effective alternative to HDT+ASCT for the treatment of R/R DLBCL in Spain.

The Health Impacts of Better Access to Axicabtagene Ciloleucel: The Case of Spain.

In this study, the health impacts of improving access to treatment with axicabtagene ciloleucel (axi-cel) was assessed in patients with relapsed/refractory diffuse large B-cell lymphoma after ≥2 lines of therapy in Spain. A partitioned survival mixture cure model was used to estimate the lifetime accumulated life years gained (LYG) and quality-adjusted life years (QALYs) per patient treated with axi-cel versus chemotherapy. Efficacy data were extracted from the ZUMA-1 trial for axi-cel and from the SCHOLAR-1 study for chemotherapy. In the base case, the incremental outcomes of axi-cel versus chemotherapy were evaluated in a cohort of 187 patients treated with CAR T-cell therapies, as reported by the "Spanish National Health System Plan for Advanced Therapies", and in the alternative scenario in the full eligible population based on epidemiological estimates (n = 490). Taking those currently treated with axi-cel, compared with chemotherapy, axi-cel provided an additional 1341 LYGs and 1053 QALYs. However, when all eligible patients (n = 490) were treated, axi-cel provided an additional 3515 LYs and 2759 QALYs. Therefore, if all eligible patients were treated with axi-cel rather than those currently treated as per the registry (n = 187), there would have been an additional 303 patients treated, resulting in an additional 2173 LYGs and 1706 QALYs in total. The lack of access in Spain has led to a loss of a substantial number of LYGs and QALYs, and efforts should be made to improve access for all eligible patients.

A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C.

BACKGROUND & AIMS: Adherence to antiviral treatment is important to achieve sustained virological response (SVR) in chronic hepatitis C (CHC). We evaluated the efficiency of a multidisciplinary support programme (MSP), based on published HIV treatment experience, to increase patient adherence and the efficacy of pegylated interferon alfa-2a and ribavirin in CHC. METHODS: 447 patients receiving antiviral treatment were distributed into 3 groups: control group (2003-2004, n=147), MSP group (2005-2006, n=131), and MSP-validation group (2007-2009, n=169). The MSP group included two hepatologists, two nurses, one pharmacist, one psychologist, one administrative assistant, and one psychiatrist. Cost-effectiveness analysis was performed using a Markov model. RESULTS: Adherence and SVR rates were higher in the MSP (94.6% and 77.1%) and MSP-validation (91.7% and 74.6%) groups compared to controls (78.9% and 61.9%) (p<0.05 in all cases). SVR was higher in genotypes 1 or 4 followed by the MSP group vs. controls (67.7% vs. 48.9%, p=0.02) compared with genotypes 2 or 3 (87.7% vs. 81.4%, p=n.s.). The MSP was the main predictive factor of SVR in patients with genotype 1. The rate of adherence in patients with psychiatric disorders was higher in the MSP groups (n=95, 90.5%) compared to controls (n=28, 75.7%) (p=0.02). The cost per patient was € 13,319 in the MSP group and € 16,184 in the control group. The MSP group achieved more quality-adjusted life years (QALYs) (16.317 QALYs) than controls (15.814 QALYs) and was dominant in all genotypes. CONCLUSIONS: MSP improves patient compliance and increases the efficiency of antiviral treatment in CHC, being cost-effective.

Clinical and economic value of sofosbuvir-based regimens in the treatment of chronic hepatitis C in Spain.

BACKGROUND: The treatment of chronic hepatitis C virus (HCV) with direct-acting antivirals has undergone a spectacular revolution and added significant value to healthcare systems and patients. The aim of the study was to evaluate the efficiency and value of Sofosbuvir (SOF)-based regimens for a target population of 85,959 chronic HCV patients treated in Spain during 2015-2019, compared to previous therapeutic strategies (peginterferon/ and ribavirin in double/triple therapy with telaprevir or boceprevir). METHODS: A previously developed lifetime Markov model was adapted to simulate the disease HCV evolution. In SOF-based regimens, all patients (100%) were treated regardless with sustained virological response (SVR) of 93-98%, obtained from real-world data. In previous therapeutic, only ≥F2 patients were treated according to clinical practice (38%) with an average SVR of 61% taken from published literature. The value was measured as clinical and economic impact in terms of avoided HCV-related mortality and liver complications; total costs and quality-adjusted life years (QALYs) applying an annual 3% discount rate. RESULTS: Compared to previous therapeutic, during lifetime, SOF-based regimens reduced decompensated cirrhosis by 89%, hepatocellular carcinoma by 77% and liver transplant by 84%, decreasing the cost associated to liver complications management in €770 million. SOF-based regimens also decreased liver-related mortality by 82%. Besides, SOF-based regimens gained 310,765/QALYs, saving €274 million (considering drugs, monitoring, and HCV management). CONCLUSION: For Spain, SOF-based regimens offer value for HCV patients in terms of lowering HCV-related liver disease burden and generating significant cost savings for the health system, contributing to the WHO goal.

Cost-Effectiveness Analysis of Axicabtagene Ciloleucel vs. Tisagenlecleucel for the Management of Relapsed/Refractory Diffuse Large B-Cell Lymphoma in Spain.

The study aimed to assess the cost-effectiveness of axicabtagene ciloleucel (axi-cel) vs. tisagenlecleucel (tisa-cel) for the treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 lines of systemic therapy in Spain. A lifetime partitioned survival mixture cure model, which comprises pre-progression, post-progression, and death health states, was used to estimate the accumulated costs and outcomes in terms of life years gained (LYG) and quality-adjusted life years (QALY). A matching-adjusted indirect comparison was used to reweight patient-level data from ZUMA-1, the pivotal clinical trial for axi-cel, to aggregate-level data from the pivotal tisa-cel trial, JULIET. The analysis was performed from the National Health System perspective, thus only direct costs were included. Sensitivity analyses (SA) were performed. Axi-cel yielded 2.74 incremental LYG and 2.31 additional QALY gained per patient compared to tisa-cel. Total incremental lifetime costs for axi-cel versus tisa-cel were €30,135/patient. The incremental cost-effectiveness ratio of axi-cel versus tisa-cel resulted in €10,999/LYG and the incremental cost-utility ratio in €13,049/QALY gained. SA proved robustness of the results. Considering the frequently assumed willingness-to-pay thresholds in Spain (€22,000/QALY and €60,000/QALY), axi-cel is a cost-effective treatment vs. tisa-cel for adult patients with R/R DLBCL in Spain.

Long-term clinical impact of introducing a human papillomavirus 16/18 AS04 adjuvant cervical cancer vaccine in Spain.

BACKGROUND: Human papillomavirus (HPV) epidemiology and screening practices vary considerably between countries and specific analyses are required to estimate the impact of HPV vaccination. This study aimed to predict the clinical benefits of introducing a bivalent HPV16/18 vaccine in Spain, where the cervical cancer (CC) incidence is 10.3 per 100 000. METHODS: A Markov model based upon the natural history of HPV and CC was developed to simulate transitions between health states, in the presence of specific screening programmes. Published data were used to reflect the Spanish situation in terms of epidemiological characteristics, screening and treatment practices. Calibration consisted of varying disease progression rates within established ranges until model predictions matched observed epidemiological data. The clinical impact of vaccinating a cohort of 12-year-old girls against HPV was assessed over their lifetime using the calibrated model. RESULTS: Vaccination of all 12-year-old girls would result in a reduction of 75% (from 0.32% to 0.08%) in the prevalence of high-grade precancerous lesions due to oncogenic HPV, and a 79% reduction in both CC cases (from 1745 to 365) and CC deaths (from 417 to 86). Assuming a vaccine coverage of 80%, the number of CC cases and deaths would decrease by 63%. Vaccination could also substantially reduce the number of screening tests and treatments required for cervical dysplasia. CONCLUSION: Our model was successfully adapted to the Spanish epidemiological environment, screening and treatment practices and predicted a substantial long-term benefit of HPV vaccination despite a low HPV prevalence in Spain.