Cost-effectiveness of Finerenone in Addition to Standard of Care for Patients with Chronic Kidney Disease and Type 2 Diabetes in China.

INTRODUCTION: Adding finerenone to current standard of care (SoC), as recommended by Chinese guidelines, has shown substantial benefit in delaying chronic kidney disease (CKD) progression and reducing cardiovascular risk in patients with CKD and type 2 diabetes (T2D) in the landmark FIDELIO-DKD trial. This study aimed to evaluate the cost-effectiveness of finerenone + SoC versus SoC alone among Chinese patients with T2D and CKD from a healthcare system perspective. METHODS: A cost-effectiveness model (FINE-CKD) has been developed and published, with health states defined for CKD stages (CKD 1/2, CKD 3, CKD 4, and CKD 5 without renal replacement therapy (RRT), dialysis, or transplant) and cardiovascular event history. Additionally, the model also considered adverse events. Transition probabilities and event risks were derived using patient-level data from Asian population analysis of FIDELIO-DKD. Since the price of finerenone after the national reimbursement drug list (NRDL) inclusion was confidential, the cost of finerenone in the model was assumed to be the same as that of SoC. Other health resource costs were gathered from literature and supplemented by physician interviews. Measured by the EQ-5D-5L questionnaire, quality of life was translated into utilities based on the Chinese EQ-5D-5L value set. RESULTS: Discounted at 5.0% annually, over a lifetime horizon, finerenone + SoC resulted in a quality-adjusted life years (QALYs) gain of 0.321 versus SoC alone (8.660 vs. 8.338 QALYs), due to a reduction in the incidence of cardiovascular events and dialysis. Total costs per patient were lower under finerenone + SoC than SoC alone (381,130 CNY vs. 392,390 CNY). As a result, finerenone + SoC was a dominant treatment strategy compared with SoC alone. Sensitivity analysis has confirmed the robustness of this study. CONCLUSION: Adding finerenone to SoC was likely to be either a dominant or cost-effective treatment option compared with SoC alone in Chinese patients with CKD and T2D.

Estimated health economic impact of conducting urine albumin-to-creatinine ratio testing alongside estimated glomerular filtration rate testing in the early stages of chronic kidney disease in patients with type 2 diabetes.

AIM: To estimate the health economic impact of undertaking urine albumin-to-creatinine ratio (UACR) testing versus no UACR testing in early stages of chronic kidney disease (CKD) progression in patients with type 2 diabetes (T2D). METHODS: An economic model, taking a UK healthcare system perspective, estimated the impact of UACR testing on additional costs, clinical benefits measured as prevented dialyses and cardiovascular-related deaths, life years gained (LYg), LYg before kidney failure, and incremental cost-effectiveness ratio (ICER). Sixteen of the 18 Kidney Disease: Improving Global Outcomes (KDIGO) heatmap categories were considered separately, and grouped in health states according to CKD risk. Results were derived for current standard-of-care and emerging CKD therapies. RESULTS: The cohort that adhered to both UACR and estimated glomerular filtration rate (eGFR) testing guidelines in early stages of CKD (n = 1000) was associated with approximately 500 LYg before kidney failure onset; costing approximately £2.5 M. ICERs across the KDIGO heatmap categories were approximately £5,000. LIMITATIONS: This model used data from a comprehensive meta-analysis that was initiated more than 10 years ago (2009). While this was the most comprehensive source identified, recent changes in the treatment landscape, patient population and social determinants of CKD will not be captured. Furthermore, a narrow approach was taken, aligning included costs with UK NHS reference materials. This means that some direct and indirect drivers of costs in late-stage disease have been excluded. CONCLUSIONS: UACR testing in the early stages of CKD is cost effective in T2D patients. Emerging therapies with the potential to slow CKD progression, mean that optimal monitoring through UACR/eGFR testing will become increasingly important for accurate identification and timely treatment initiation, particularly for the highest-risk A3 category.

Real-world evidence for steroidal mineralocorticoid receptor antagonists in patients with chronic kidney disease.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) were shown to delay chronic kidney disease (CKD) progression in patients with hypertension and/or heart failure (HF) and proteinuria. OBJECTIVE: We conducted a systematic literature review on real-world evidence to identify the literature gaps related to the efficacy and safety outcomes of MRAs administered to CKD patients. RESULTS: A total of 751 records were identified of which, 23 studies (26 publications) were analyzed. Studies included heterogeneous populations, including the overall CKD, CKD and diabetes, CKD and HF, and CKD and a history of cardiovascular disease. Most of the studies were small and non-rigorous, resulting in a notable lack of evidence in these populations. In the overall CKD population, steroidal MRAs resulted in a significant or sustained eGFR reduction but no efficacy in delaying progression to end-stage kidney disease. No cardiovascular protection was found. Results for all-cause mortality and hospitalization for HF were inconsistent; however, the longest follow-up studies indicate similar or lower incidence for spironolactone non-users. Most results consistently reported a higher incidence of hyperkalemia among patients on steroidal MRAs in all CKD stages, and side effects led to high discontinuation rates in the real-world setting. CONCLUSIONS: Despite the limited availability of evidence on the effectiveness and safety of steroidal MRAs in CKD patients and subgroups with diabetes, HF or history of cardiovascular disease, MRAs were shown to have a limited effect on renal and cardiovascular outcomes. Gaps in the evidence regarding the efficacy and safety of MRAs are particularly relevant in diabetic CKD patients; therefore, further research is warranted.

Validation of the FINE-CKD model for future health technology assessments for finerenone in patients with chronic kidney disease and type 2 diabetes.

BACKGROUND: The FINE-CKD model was developed to estimate the cost-effectiveness of finerenone in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). OBJECTIVE: To perform internal and external validation by comparing the model estimates with trial results and outcomes from other models. METHODS: Incidence rates from trials were compared with the model predictions. Statistical tests were then performed to assess whether modeled event rates aligned with trial observations. A cross-validation was also performed using the online version of the SHARP CKD-Cardiovascular Disease (SHARP CKD-CVD) model, with population characteristics from the finerenone trials analyzed. Where no finerenone data were available, the default SHARP CKD-CVD values were used. Comparison of the results considered the ranges from both models. RESULTS: The outcomes of the FINE-CKD model reflect the event rates observed in the trials. Based on the results of the statistical tests, the hypothesis of no difference between observed and modeled events cannot be rejected for any of the outcomes. The results of the FINE-CKD model are within the ranges from the SHARP CKD-CVD model. Disease progressions align across the models; however, incident kidney failure events in the SHARP CKD-CVD model were higher. This can be explained by simulation of more severely affected patients in the SHARP CKD-CVD model. CONCLUSIONS: This study demonstrates that the FINE-CKD model adequately reflects the clinical data and provides reliable extrapolation relative to the existing predictive tools while also being conservative in its approach.

FINE-CKD model to evaluate economic value of finerenone in patients with chronic kidney disease and type 2 diabetes.

BACKGROUND: Chronic kidney disease (CKD) is a progressive and irreversible disease often associated with type 2 diabetes (T2D). CKD is associated with an elevated risk of cardiovascular (CV) events, increased mortality, and diminished quality of life. Finerenone is a new treatment for patients with CKD and T2D that delays CKD progression and reduces CV complications. OBJECTIVE: To describe the approach and structure of a costeffectiveness model for finerenone for patients with CKD and T2D and compare it with existing economic models in CKD. METHODS: A de novo cost-effectiveness model (FINE-CKD model), reflective of FIDELIO-DKD results, was developed for finerenone. The FINE-CKD model was designed and implemented in accordance with published guidance on modeling and was developed with input from economic and clinical experts. The final model approach was evaluated against existing modeling structures in CKD identified through a systematic literature review. RESULTS AND CONCLUSIONS: The FINE-CKD model structure follows recommended modeling guidelines and has been designed in accordance with the best practices of modeling in CKD, while also incorporating important features of the FIDELIO-DKD design and results. The approach is consistent with the published literature, ensuring transparency and minimizing uncertainty that can arise from unnecessary complexity. The FINE-CKD model allows for reliable assessment of benefits and costs related to the use of finerenone in patients with CKD and T2D, and it is a reliable assessment of cost-effectiveness.

Targeted literature review of the burden of illness in patients with chronic kidney disease and type 2 diabetes.

OBJECTIVES: Chronic kidney disease (CKD) is increasingly prevalent among patients with type 2 diabetes (T2D). CKD is associated with increased mortality rates, clinical and humanistic burden, and substantial health care costs in the T2D population. The objective of this review was to summarize the burden of illness among patients with CKD and T2D, including the profile of patients, incidence, prevalence, mortality, progression, diagnosis and screening rates, and cardiovascular (CV) events. METHODS: A targeted literature review of published studies was conducted using Embase; Medline; Medline In-Process Citations, Daily Update, and Epub Ahead of Print; Igaku Chuo Zasshi databases; and 7 websites. Methods recommended by the Cochrane collaboration handbook, the Centre for Reviews and Dissemination, and the Joanna Briggs Institute critical appraisal checklist were employed. RESULTS: A total of 1290 full-text articles were reviewed for eligibility and 73 were included in this analysis. Patient profiles indicated older age was associated with more severe disease and number of comorbidities. The definition of kidney disease varied between studies reporting incidence and prevalence, with reported values up to 37.0% and 43.5% for incidence and prevalence, respectively. CKD among patients with T2D contributed to higher mortality rates. Higher disease progression rates were associated with higher albuminuria and lower estimated glomerular filtration rate levels. The available literature suggested annual screening rates for CKD declined over time. CV events were reported to have a substantial effect on morbidity and resource use. CONCLUSIONS: This review highlights the burden of CKD among patients with T2D and underscores a need for new treatment alternatives to reduce the burden of disease.

Health economic evaluation of rivaroxaban in the treatment of patients with chronic coronary artery disease or peripheral artery disease.

AIMS: In the COMPASS trial, rivaroxaban 2.5 mg twice daily (bid) plus acetylsalicylic acid (ASA) 100 mg once daily (od) performed better than ASA 100 mg od alone in reducing the rate of cardiovascular disease, stroke, or myocardial infarction (MI) in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). A Markov model was developed to assess the cost-effectiveness of rivaroxaban plus ASA vs. ASA alone over a lifetime horizon, from the UK National Health System perspective. METHODS AND RESULTS: The base case analysis assumed that patients entered the model in the event-free health state, with the possibility to experience ≤2 events, transitioning every three-month cycle, through acute and post-acute health states of MI, ischaemic stroke (IS), or intracranial haemorrhage (ICH), and death. Costs, quality-adjusted life-years (QALYs), life years-all discounted at 3.5%-and incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted, as well as scenario analyses. In the model, patients on rivaroxaban plus ASA lived for an average of 14.0 years with no IS/MI/ICH, and gained 9.7 QALYs at a cost of £13 947, while those receiving ASA alone lived for an average of 12.7 years and gained 9.3 QALYs at a cost of £8126. The ICER was £16 360 per QALY. This treatment was cost-effective in 98% of 5000 iterations at a willingness-to-pay threshold of £30 000 per QALY. CONCLUSION: This Markov model suggests that rivaroxaban 2.5 mg bid plus ASA is a cost-effective alternative to ASA alone in patients with chronic CAD or PAD.

Lifetime cost effectiveness of a through-school nutrition and physical programme: Project Energize.

Project Energize, a multicomponent through-school physical activity and nutrition programme, is delivered to all primary school children in the Waikato region. The programme aim is to improve the overall health and reduce the rate of weight gain of all Waikato primary school children. An existing economic model was used to extrapolate the programme effects, initial costs, lifetime health treatment cost structures, quality-adjusted-life-years gained and increased life expectancy to the general and Maori child population of New Zealand. In March 2011, a sample of 2474 younger (7.58 ± 0.57 years, mean ± SD) and 2330 older (10.30 ± 0.51 years) children (36% Maori) attending Energize schools had body mass index measured and compared using mixed effect modelling with unEnergized comparison children from 2004 and 2006 from the same region. In 2011 the median body mass index reduction compared with the comparison younger children was -0.504 (90% CI -0.435 to -0.663) kg/m(2) and in the older children -0.551 (-0.456 to -0.789) kg/m(2). In 2010 there were 42,067 children attending Energize schools and in the same year NZ$1,891,175 was spent to deliver the programme; a cost of $44.96/child/year. Compared to the comparison children the increment in cost/quality-adjusted-life-year gained was $30,438 for the younger and $24,690 for the older children, and lower for Maori (younger $28,241, older $22,151) and for the middle socioeconomic status schools ($23,211, $17,891). Project Energize would improve quality and length of life and when compared with other obesity prevention programmes previously assessed with this model, it would be relatively cost-effective from the health treatment payer's perspective.

Changing epidemiology of invasive pneumococcal disease in Australian children after introduction of a 7-valent pneumococcal conjugate vaccine.

OBJECTIVE: To evaluate trends in the incidence and serotype profile of invasive pneumococcal disease (IPD) in Australian children under 2 years of age after the introduction of the 7-valent pneumococcal conjugate vaccine (7vPCV). DESIGN AND SETTING: Analysis of incidence rates calculated using IPD surveillance data (including age, Indigenous status and serotype of the pneumococcal isolate) from 2002 to 2007 obtained from the National Notifiable Diseases Surveillance System and population estimates obtained from the Australian Bureau of Statistics. MAIN OUTCOME MEASURES: Trends in IPD incidence among Indigenous and non-Indigenous children between 2002 and 2007; change in the serotype profile of IPD in non-Indigenous children after the introduction of universal 7vPCV vaccination in 2005. RESULTS: Overall incidence of IPD decreased by 74% in all children < 2 years of age between 2002 and 2007 (P < 0.001). While the incidence of IPD caused by 7vPCV serotypes decreased significantly among both Indigenous and non-Indigenous children, the incidence of non-7vPCV serotype IPD increased significantly in non-Indigenous children (from 9.7 to 15.7 per 100 000, P < 0.001). Compared with a pre-vaccination period (2002-2004), the 2007 incidence of serotype 19A IPD in non-Indigenous children increased significantly (from 2.7 to 8.6 per 100 000, P < 0.001). In 2007, 19A was the predominant serotype causing IPD (37.7%) in all children aged < 2 years. CONCLUSIONS: The overall incidence of IPD decreased from 2002 to 2007, primarily driven by a reduction in IPD caused by 7vPCV serotypes. However, this was partially offset by a significant increase in the incidence of IPD caused by non-7vPCV serotypes, particularly 19A, in non-Indigenous children.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer: the Canadian perspective.

OBJECTIVES: Radioiodine ablation for the treatment of thyroid cancer is traditionally performed after preparing patients by inducing hypothyroidism. Exogenous stimulation of thyroid-stimulating hormone (TSH) using recombinant human TSH (rhTSH) avoids hypothyroidism and hastens the clearance of radioiodine from the patient. These advantages are achieved without jeopardizing the success rate of remnant ablation. An economic analysis was performed to place the increased acquisition cost of rhTSH in the context of the health benefits achieved and the earlier discharge from radioprotection. METHODS: Markov modeling, using 17 individual weekly cycles, was used to assess the incremental cost per quality-adjusted life-year (QALY) associated with exogenous stimulation. Clinical inputs were largely sourced from a multicenter, randomized, controlled trial comparing remnant ablation success after either rhTSH or hypothyroid preparation. The model applied Canadian unit costs, taking a societal perspective. Additional costs associated with rhTSH were considered in the context of the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier administration of ablation after surgery, and earlier discharge from the radio-protective ward because of faster radioiodine clearance following rhTSH preparation. The model duration avoided the need for discounting. RESULTS: The additional benefits of rhTSH (0.0576 QALY) are obtained with an incremental cost of CDN$87, generating an incremental cost per QALY of CDN$1520. Deterministic one-way and two-way sensitivity analyses demonstrated the result to be robust. CONCLUSIONS: The use of rhTSH before radioiodine ablation represents a reasonable allocation of costs, with the benefits to patients, hospitals, and society as a whole, obtained at modest cost.

Using recombinant human thyroid-stimulating hormone for the diagnosis of recurrent thyroid cancer.

BACKGROUND: Recombinant human thyroid-stimulating hormone (rhTSH) has been suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer, instead of the current practice of thyroid hormone (THT) withdrawal. METHODS: An evidenced-based literature review was used as the basis for a cost-utility, decision-analytic model. Outcome measures were safety, efficacy (diagnostic performance and quality of life) and cost effectiveness of rhTSH. RESULTS: The literature search identified six comparative studies of rhTSH versus THT withdrawal. The most common adverse events associated with the use of rhTSH were headache (3.5-11.1%) and nausea (7.7-17%). When used as a diagnostic agent, the unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively. Thus the use of rhTSH instead of THT withdrawal would result in a reduction in diagnostic accuracy, with 11% of patients' disease status being misclassified. Use of rhTSH resulted in a higher quality of life in the period prior to diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic performance, patient compliance to follow-up and modified quality of life were modelled over a 5 year time-frame, the incremental cost per QALY of rhTSH relative to THT withdrawal was $51 344.42. CONCLUSIONS: The use of rhTSH as a diagnostic agent appears to be safe but less diagnostically accurate and less cost-effective (on whole of healthcare cost basis) when used in the follow-up of patients with thyroid cancer who have had a previous negative radioiodine scan after thyroid hormone withdrawal.