Cost-effectiveness of nivolumab and ipilimumab versus pembrolizumab and axitinib in advanced renal cell carcinoma with intermediate or poor prognostic risk: a Brazilian private healthcare system perspective.

OBJECTIVE: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments. METHODS: A three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon. In the absence of head-to-head comparisons between NIVO + IPI and PEM + AXI, clinical data for NIVO + IPI was obtained from CheckMate 214 (NCT02231749) and for PEM + AXI from KEYNOTE-426 (NCT02853331). A matching-adjusted indirect comparison was conducted to account for the imbalance of treatment effect modifiers between the trials. Patient characteristics, resource use, health state utilities, and costs were based on Brazilian-specific sources. Costs and health outcomes were both discounted by 5% annually in line with Brazilian guidelines. The robustness of the results was evaluated through extensive sensitivity analysis and scenario analyses. RESULTS: When comparing the matched versus unmatched OS, PFS, and TTD curves there was no noteworthy difference. NIVO + IPI was associated with cost savings (R$ 350,232), higher LYs (5.54 vs. 4.61), and QALYs (4.74 vs. 3.76) versus PEM + AXI, resulting in NIVO + IPI dominating PEM + AXI. Key model drivers were the treatment duration for PEM, NIVO, and AXI. NIVO + IPI remained dominant in all scenario analyses, which indicated that model results were robust to alternative modelling inputs or assumptions. CONCLUSIONS: This analysis shows that NIVO + IPI is estimated to be a life-extending and potentially cost-saving 1 L treatment option when compared with PEM + AXI for intermediate/poor-risk a RCC patients in the Brazilian private healthcare system.

Immunotherapy-based first-line treatment of intermediate- and poor-risk advanced renal cell carcinoma: number needed to treat and cost of preventing an event from the perspective of the Brazilian private healthcare system / Tratamento baseado em imunoterapia para primeira linha do carcinoma renal avançado com risco intermediário ou alto: número necessário a tratar e custo para prevenir um evento na perspectiva do sistema privado de saúde brasileiro

Objective: To perform an analysis over time of the number needed to treat (NNT) and the cost of preventing an event (COPE) for nivolumab + ipilimumab (NIVO+IPI) and pembrolizumab + axitinib (PEMBRO+AXI) as first-line treatments for advanced renal cell carcinoma patients with intermediate or poor-risk, under the Brazilian private healthcare system perspective. Methods: The NNT for overall survival (OS) and progression-free survival (PFS) from 12-month to maximum available follow-up from CheckMate 214 and KEYNOTE-426 studies were used to estimate the COPE. Treatment costs were estimated considering the labeled dosing and median PFS as a proxy for treatment duration. Results: The OS NNT for NIVO+IPI decreased from 12 to 8 and for PEMBRO+AXI increased slightly from 7 to 8 at 12 and 42 months, respectively. For PFS, NNT for NIVO+IPI decreased from 15 to 6, and for PEMBRO+AXI increased from 7 to 10 at 12 and 30 months. The estimated treatment cost is R$ 638,620 for an estimated median of 11.2 months of NIVO+IPI treatment and R$ 966,818 for 13.8 months of PEMBRO+AXI treatment. COPE for OS at 12 and 42 months was R$ 7,663,440 and R$ 5,108,960 with NIVO+IPI and R$ 6,047,417 and R$ 7,734,547 with PEMBRO+AXI. For PFS, COPE at 12 and 30 months was R$ 9,579,300 and R$ 3,831,720 with NIVO+IPI and R$ 6,047,417 and R$ 9,668,184 with PEMBRO+AXI. Conclusions: Treatment with NIVO+IPI results in lower COPE than PEMBRO+AXI from month 18 onwards, driven by lower treatment costs and improved NNT over time with NIVO+IPI

Objetivo: Analisar ao longo do tempo o número necessário a tratar (NNT) e o custo para prevenir um evento (COPE) para nivolumabe + ipilimumabe (NIVO+IPI) e pembrolizumabe + axitinibe (PEMBRO+AXI) na primeira linha de tratamento do carcinoma de células renais avançado com risco intermediário ou alto na perspectiva do sistema suplementar de saúde brasileiro. Métodos: O NNT para sobrevida global (SG) e sobrevida livre de progressão (SLP) para 12 meses até o máximo de tempo de seguimento disponível dos estudos CheckMate 214 e KEYNOTE-426 foi usado para estimar o COPE. Custos de tratamento foram estimados considerando a dosagem em bula e a mediana de SLP como aproximação para duração de tratamento. Resultados: O NNT de SG para NIVO+IPI reduziu de 12 para 8 e para PEMBRO+AXI subiu de 7 para 8 em 12 e 42 meses, respectivamente. Para SLP, NIVO+IPI teve redução de 15 para 6 e para PEMBRO+AXI aumentou de 7 para 10 em 12 e 30 meses. O custo estimado é de R$ 638.620 para mediana de 11,2 meses de tratamento com NIVO+IPI e de R$ 966.818 para 13,8 meses com PEMBRO+AXI. O COPE para SG foi de R$ 7.663.440 e R$ 5.108.960 com NIVO+IPI e de R$ 6.047.417 e R$ 7.734.547 com PEMBRO+AXI para 12 e 42 meses. Para SLP, foi de R$ 9.579.300 e R$ 3.831.720 com NIVO+IPI e de R$ 6.047.417 e R$ 9.668.184 com PEMBRO+AXI em 12 e 30 meses. Conclusões: O tratamento com NIVO+IPI resulta em menor COPE, em comparação com PEMBRO+AXI, a partir de 18 meses de seguimento, justificado por menor custo de tratamento e melhora do NNT ao longo do tempo com NIVO+IPI

A review of health utilities using the EQ-5D in studies of cardiovascular disease.

BACKGROUND: The EQ-5D has been extensively used to assess patient utility in trials of new treatments within the cardiovascular field. The aims of this study were to review evidence of the validity and reliability of the EQ-5D, and to summarise utility scores based on the use of the EQ-5D in clinical trials and in studies of patients with cardiovascular disease. METHODS: A structured literature search was conducted using keywords related to cardiovascular disease and EQ-5D. Original research studies of patients with cardiovascular disease that reported EQ-5D results and its measurement properties were included. RESULTS: Of 147 identified papers, 66 met the selection criteria, with 10 studies reporting evidence on validity or reliability and 60 reporting EQ-5D responses (VAS or self-classification). Mean EQ-5D index-based scores ranged from 0.24 (SD 0.39) to 0.90 (SD 0.16), while VAS scores ranged from 37 (SD 21) to 89 (no SD reported). Stratification of EQ-5D index scores by disease severity revealed that scores decreased from a mean of 0.78 (SD 0.18) to 0.51 (SD 0.21) for mild to severe disease in heart failure patients and from 0.80 (SD 0.05) to 0.45 (SD 0.22) for mild to severe disease in angina patients. CONCLUSIONS: The published evidence generally supports the validity and reliability of the EQ-5D as an outcome measure within the cardiovascular area. This review provides utility estimates across a range of cardiovascular subgroups and treatments that may be useful for future modelling of utilities and QALYs in economic evaluations within the cardiovascular area.