Cost-Utility Analysis Comparing Pegcetacoplan to Anti-C5 Monoclonal Antibodies in the Treatment of Paroxysmal Nocturnal Hemoglobinuria.

Background: Paroxysmal nocturnal hemoglobinuria is a rare, acquired disease characterized by hemolytic episodes and associated with significant clinical burden. The introduction of C5 inhibitory monoclonal antibodies (C5i) represented a major breakthrough in PNH treatment, effectively reducing intravascular hemolysis (IVH) but showing limited impact on extravascular hemolysis (EVH). In 2021, the C3 inhibitor pegcetacoplan was approved by EMA and recently reimbursed in Italy, which also has the advantages in the reduction of both IVH and EVH, increasing hemoglobin values and simultaneously improving the quality of life and fatigue of patients. A cost-utility analysis was developed to compare pegcetacoplan to C5i (eculizumab and ravulizumab) in the PNH population who remain anemic after treatment with C5i for at least 3 months. Materials and Methods: The analysis employed a Markov model with a 5-year time horizon whereby patients can transition among 3 PNH health states, adopting the perspective of the Italian NHS. Efficacy data were sourced from the PEGASUS study, with drug prices reflecting ex-factory costs. Additionally, costs associated with resource utilization, adverse events, and complications were estimated based on outpatient and hospital care rates, excluding indirect expenses. Utility and disutility values related to transfusions were also considered, with pegcetacoplan allowing for dose escalation. Results: The cumulative cost of treatment per individual patient at 5 years was estimated to be €1,483,454 for pegcetacoplan, €1,585,763 for eculizumab, and €1,574,826 for ravulizumab. Pegcetacoplan demonstrated a superior increase in quality-adjusted life years (QALYs) compared to both eculizumab (0.51 increase) and ravulizumab (0.27 increase). Furthermore, pegcetacoplan showed a reduction in complication management costs (€22,891 less compared to eculizumab and €22,611 less compared to ravulizumab) and lower transfusion-related expenses (€14,147 less than both C5i treatments). Conclusion: Pegcetacoplan emerged as the dominant strategy in this analysis, being more effective, less expensive and improves quality of life in the analyzed population affected by PNH.

Budget impact analysis for avatrombopag in the treatment of chronic primary immune thrombocytopenia in adult patients refractory to other treatments.

Introduction: Primary immune thrombocytopenia is a rare autoimmune disease characterised by a decreased platelet count resulting in an increased risk of bleeding events and even life-threatening haemorrhages. Thrombopoietin receptor agonists (TPO-RAs) are the standard of care second-line therapy for adult patients with chronic immune thrombocytopenia. The first TPO-RAs approved and reimbursed in Italy, eltrombopag and romiplostim, while effective, pose some issues in terms of safety (e.g., hepatotoxicity) or general management (e.g., dietary restrictions). Avatrombopag, an effective and well-tolerated TPO-RA, was recently granted reimbursement. Methods: A 3-year (2023-2025) budget impact analysis (BIA) was conducted to estimate its impact on the Italian National Health Service (NHS). Two scenarios were compared, of which one represents the current situation, without avatrombopag, and the other provides for an increasing market share of avatrombopag (up to 26.6%). Results: BIA shows that the increase in the use of avatrombopag correlates with savings for NHS: in the first year, saving would be €1,300,564, increasing to €2,774,210 in the third year, for a total of €6,083,231 over the 3-year period. The sensitivity analysis confirmed these savings in the scenario with avatrombopag. Conclusions: Based on this BIA, the introduction and reimbursement of avatrombopag is an efficient and advantageous choice for the Italian NHS.

Cost analysis of extended half-life recombinant factor IX products in the treatment of haemophilia B in Italy: an update.

Haemophilia B (HB) is a rare disease which may lead to chronic disabling arthropathy, resulting in a significant clinical, social and economic impact. In recent years, new extended half-life (EHL) factor IX concentrates produced by recombinant technology (rFIX) have been developed. They have shown significantly prolonged half-life as compared to other rFIX products and improved bleeding control when used as prophylaxis. To date, EHL rFIX products reimbursed in Italy are a recombinant coagulation factor IX produced with Fc technology (rFIXFc) and a recombinant fusion protein containing rFIX fused with recombinant albumin (rIX-FP). The results of extension studies with injection intervals with a median of almost every 14 days for the complete individualized interval prophylaxis (IP) group on rFIXFc and 21 days for a selected subgroup of patients on rIX-FP have recently been published. The aim of this analysis was to estimate the cost of prophylactic treatment with rFIXFc and rIX-FP in adult patients, in the light of new clinical evidence and current average prices in Italy. The cost of therapy was estimated on the basis of the results of extension studies, the average prices reported in regional drug tenders and assuming an average patient weight of 70 kg. The analysis estimated a cost per patient/year between €224,407 and €230,355 for rFIXFc and between €242,259 and €368,587 for rIX-FP. The sensitivity analysis confirmed the robustness of the results. The use of rFIXFc over rIX-FP proves to be the least expensive choice for the treatment of HB in Italy.

Budget impact analysis of extended half-life recombinant factor IX (rFIXFc) in the treatment of haemophilia B.

Introduction: Prophylaxis with factor IX (FIX) concentrates, produced by recombinant DNA technology (rFIX) or human plasma-derived concentrates, is the treatment of choice for haemophilia B (HB); rFIX covalently fused to the Fc domain of human immunoglobulin G1 (rFIXFc) allows for prophylaxis/treatment with one infusion every 7-14 days. The purpose of this study is to quantify the financial impact of prophylaxis with rFIXFc vs. other approved rFIX and reimbursed for treatment of HB in Italy. Methods: The number of patients was estimated according to Italian epidemiological data and use of rFIX. Dose and frequency of administration used for weekly prophylaxis were those recommended in the Summary of Product Characteristics (SPC), while clinical trials and literature data were used to calculate bleeding rates and management. Drug costs were calculated using regional ex-factory net prices. In the model, a reference scenario (Reference) vs. an alternative scenario (Alternative) were created to account for introduction of rFIXFc, estimating an increasing trend of the market share of rFIXFc in a 3-year timeframe. The analysis was developed in the perspective of the National Health Service and included healthcare costs related to rFIX for prophylaxis and resolution of bleeding events. Results: The model estimated an overall cumulative expenditure (years 1-3) of €209,453,646 for the Reference and €207,465,568 for Alternative scenarios, with calculated cumulative savings of €1,988,068. Conclusions: The increasing use of rFIXFc as a substitute for other rFIX concentrates in the treatment of HB can represent a financially viable choice for the Italian National Health Service while ensuring effective control of bleeding.

Cost of illness of urothelial bladder cancer in Italy.

BACKGROUND: Urothelial bladder cancer (UBC) is the ninth most common cancer worldwide. In Italy, the prevalence of the disease is approximately 10%, making it the fourth most prevalent cancer in the country. The increase in prevalence requires continuous surveillance and care, resulting in a significant burden on Italian National Health Service, making any improvement to the strategy for diagnosing and treating this disease important to the medical and scientific community. The aim of this study was to evaluate the UBC cost of illness in the Italian context, collecting the total costs of the disease. METHODS: An economic analysis was carried out in the context of the National Health Service, using data collected from six centers, in order to evaluate direct costs in terms of outpatient, inpatient, and emergency care; pharmaceuticals and follow-up procedures; and indirect costs in terms of productivity losses. Data were collected through aggregated form reports, focusing on patients with an existing diagnosis of UBC who were treated in the last year. The Italian Association of Medical Oncology (AIOM) guidelines were used to identify diagnostic and therapeutic procedures. Statistical analysis was conducted to explore variations among centers. RESULTS: The weighted mean total annual cost per patient was € 3,591, where the cost for superficial disease was € 3,252 and that for metastatic disease was € 606. The analysis confirmed a proportional relation between disease severity and disability grade. The UBC cost of illness, considering prevalence and incidence data coming from the 2016 AIOM/Italian Association of Cancer Registries report, was € 1,187,036,344. Indirect costs accounted to 44%, represented by estimated productivity losses. CONCLUSION: Our analysis represents the first economic study of UBC in the Italian context, as well as the first real-life evidence of the current therapeutic algorithm. This study opens the possibility for further analysis on the indirect cost components that represent a great burden for the society, especially for those in the severest stages of the disease with high disability grades.

Cost-consequence analysis of long-term prophylaxis in the treatment of von Willebrand disease in the Italian context.

PURPOSE: Prophylaxis with von Willebrand factor (VWF)/factor VIII (FVIII) concentrates is a potential approach for patients with severe von Willebrand disease (VWD). As far as we are aware, to date there have been no pharmacoeconomic analyses in order to assess the economic impact of treatments for severe VWD. The analysis presented here estimates the cost-benefit ratio of VWF with a low FVIII content when compared with VWF/FVIII concentrates currently used in Italy for long-term prophylaxis in patients with severe VWD. METHODS: A cost-consequence analysis was undertaken to assess the economic impact of the treatment of severe VWD from the perspective both of the Italian National Health Service and society. The analysis was based on four case reports of long-term prophylaxis with VWD with VWF/FVIII concentrates and VWF with a low FVIII content. The costs per patient included direct and indirect costs for each treatment. RESULTS: Considering the four case reports, health care costs (without cost of treatment) and indirect costs per patient per year were lower with VWF with a low FVIII content than VWF/FVIII concentrates. The total health care costs (without cost of treatment) and indirect costs avoided with VWF with a low FVIII content per patient per year ranged from €2,295 to €17,530 and from €1,867 to €4,978, respectively. CONCLUSION: VWF with a low FVIII content seems to be a cost-effective treatment option for patients with severe VWD. Although the drug cost per se is higher, the use of VWF with a low FVIII content is associated with decreased consumption of hospital resources and fewer lost working days due to bleedings and consequently with an improvement of the quality of life of the patients.