A cost-effectiveness analysis of ruxolitinib versus best alternative therapy for patients with steroid-refractory chronic graft-versus-host disease aged > 12 years in Singapore.

BACKGROUND: Approximately 30-70% of patients who have undergone allogeneic (allo) hematopoietic stem cell transplantation (HSCT) eventually experience chronic graft-versus-host disease (cGVHD). Patients who develop steroid-refractory (SR)-cGVHD are the most severely impacted due to significant disease and financial burden. There remains an unmet need for safe, efficacious, and accessible treatments for these patients. The objective of this study was to determine the cost effectiveness of ruxolitinib for treatment of SR-cGvHD from the Singapore healthcare system perspective. METHODS: Based on data from the REACH3 randomized open-label trial, a semi-Markov model was developed to evaluate cost-effectiveness of ruxolitinib compared with investigators' choice of best alternative therapy (BAT) for treatment of patients > 12 years of age with SR-cGVHD in Singapore over a 40-year time horizon. The model only considered direct medical-care costs related to the treatment of SR-cGVHD and reported them in Singapore Dollars (SGD). Half-cycle correction was applied to all costs and outcomes, which were discounted at 3%. Probabilistic sensitivity analysis (PSA), one-way sensitivity analysis (OWSA), and scenario analysis were conducted to explore the drivers of uncertainty in the model. RESULTS: In the deterministic base case, more life years (LY; 10.28 vs. 9.42) and quality-adjusted life years (QALYs; 7.31 vs. 6.51) were gained with ruxolitinib than BAT at higher costs (SGD 303,214 vs. SGD 302,673) leading to an incremental cost-effectiveness ratio (ICER) of SGD 677/QALY. At a willingness-to-pay threshold of SGD 75,000/QALY gained, PSA found that ruxolitinib had a 78.52% probability of being cost-effective. Findings were sensitive to variations in non-responder utilities in the BAT arm and duration of BAT treatment in the OWSA, or comparison to either methotrexate (MTX) or mycophenolic acid as a single comparator in the scenario analysis. ICERs remained lower than SGD 75,000/QALY in all other tested variations and scenarios. CONCLUSION: Ruxolitinib is likely to be cost-effective from Singapore healthcare system's perspective for patients with SR-cGVHD, which is promising in the management of patients with unmet clinical needs.

Cost-Effectiveness and Budget Impact Analyses of Tisagenlecleucel in Pediatric and Young Adult Patients with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia from the Singapore Healthcare System Perspective.

Purpose: Children and young adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) have poor survival due to ineffective therapy options. The newly approved chimeric antigen receptor T-cell (CAR-T) therapy, tisagenlecleucel, has demonstrated improved survival but at a high up-front cost. The study aims to evaluate the cost-effectiveness and budget impact of tisagenlecleucel versus salvage chemotherapy regimen (SCR) or blinatumomab (BLN) for the treatment of pediatric and young adult patients with relapsed/refractory B-cell ALL from the Singapore healthcare system perspective. Patients and Methods: A three-health state partitioned survival model was constructed to analyze the cost-effectiveness of tisagenlecleucel vs SCR/BLN with/without allogenic hematopoietic stem cell transplantation (allo-HSCT) over a lifetime period. Clinical efficacy for tisagenlecleucel, SCR and BLN were based on pooled data from ELIANA, ENSIGN and B2101J trials, the study by von Stackelberg et al 2011, and MT103-205 respectively. Medical costs from pre-treatment until terminal care, including treatment, side effects, follow-up, subsequent allo-HSCT and relapse, were considered. Incremental cost-effectiveness ratios (ICERs) were estimated as the incremental costs per quality-adjusted life-year (QALY) gain. Additionally, the financial impact of tisagenlecleucel introduction in Singapore was estimated, comparing the present treatment scenario (without tisagenlecleucel) with a future scenario (with tisagenlecleucel), over 5 years. Results: In the base-case analysis, tisagenlecleucel treatment demonstrated cost-effectiveness with an ICER of S$45,840 (US$34,762) per QALY (vs SCR) and S$51,978 (US$39,315) per QALY (vs BLN). The estimated budget ranges from S$477,857 (US$361,438) to S$1.4 million (US$1.05 million) annually for the initial 5 years. Conclusion: Tisagenlecleucel is likely to be a cost-effective treatment option with limited budget implications while treating r/r ALL patients who have failed at least 2 lines of prior therapies.

Enabling access to molecular monitoring for chronic myeloid leukemia patients is cost effective in China.

OBJECTIVE: To determine the cost effectiveness of molecular monitoring in patients with chronic myeloid leukemia in the chronic phase (CML-CP) compared to no molecular monitoring from a Chinese payer perspective. METHODS: Analyses were conducted using a semi-Markov model with a 50-year time horizon. Population data from multicenter registry-based studies of Chinese patients with CML-CP informed the model. Transition probabilities were based on time-to-event data from the literature. Utility values were obtained from published studies and were assumed to be the same for patients with and without molecular monitoring. Costs were based on values commonly used in the Chinese healthcare system, including drug acquisition, drug administration, follow-up, treatment for disease progression, molecular monitoring, and terminal care costs, and were in the local currency (2020 Chinese Yuan RMB [¥]). Outcomes were total life-years (LYs) and quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Molecular monitoring was dominant to no molecular monitoring, with increased LYs (1.52) and QALYs (1.90) and costs savings (¥93,840) over a lifetime compared to no monitoring in discounted analyses. The opportunity of patients that receive molecular monitoring to discontinue treatment during treatment-free remission, an opportunity not afforded to those without molecular monitoring, was the principle driver of this result. Results were similar across multiple clinical scenarios. Particularly, molecular monitoring remained dominant even if the proportion of patients achieving deep molecular response (DMR) was reduced by 10%-30%, or the proportion of patients maintaining DMR for 1 year was reduced by 10%-30% or increased by 10%. Cost savings in these scenarios ranged from ¥62,230 to ¥103,964. CONCLUSIONS: Overall, this analysis demonstrates that adherence to guideline recommendations of regular molecular monitoring of patients with CML-CP treated with TKIs provides significant clinical benefit that leads to substantial cost savings compared to no molecular monitoring from the perspective of a Chinese payer. In a time where healthcare systems have limited resources to allocate to optimal patient care, investment in molecular monitoring is an ideal choice for improving patient benefits at a reduced cost.

Cost-effectiveness and budget impact analyses of tisagenlecleucel in adult patients with relapsed or refractory diffuse large B-cell lymphoma from Singapore's private insurance payer's perspective.

BACKGROUND: Patients experiencing relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) have limited treatment options and poor prognosis. Tisagenlecleucel (TIS) has shown improved clinical outcomes, but at a high upfront cost. Singapore has a multi-payer healthcare system where private insurance is one of the major payers. This study evaluated the cost-effectiveness and budget impact of TIS against salvage chemotherapy regimen (SCR) for treating r/r DLBCL patients who have failed ≥2 lines of systemic therapy from Singapore's private insurance payer's perspective. METHODS: Over a life-time horizon, a partitioned survival model with three health-states was developed to evaluate the cost-effectiveness of TIS vs. SCR with or without hematopoietic stem cell transplantation (HSCT). Efficacy inputs for TIS and SCR were based on 43 months of observation data from pooled JULIET and UPenn trials, and CORAL extension studies respectively. Direct costs for pre-treatment, treatment, adverse events, follow-up, subsequent-HSCT, relapse, and terminal care were included. Incremental cost-effectiveness ratios (ICERs) were calculated as the total incremental costs per quality-adjusted life-year (QALY) gained. Additionally, the financial implication of introducing TIS in Singapore from a private payer's perspective was analyzed, comparing the current treatment pathway (without TIS) with a future scenario (with TIS) over 5 years. RESULTS: Compared with SCR, TIS was the dominant option, with cost savings of S$8,477 alongside an additional gain of 2.78 QALYs in privately insured patients who shifted from private to public hospitals for TIS treatment. Scenario analyses for patients starting in public hospitals show ICERs of S$99,623 (no subsidy) and S$133,261 (50% subsidy for SCR treatment, no subsidy for TIS), supporting the base case. The projected annual budget impact ranges from S$850,000 to S$3.4 million during the first 5 years. CONCLUSIONS: TIS for treating r/r DLBCL patients who have failed ≥2 lines of systemic therapies, is likely to be cost effective with limited budget impact.