Swedish Healthcare Perspective Research Articles

Cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy for treating previously treated advanced endometrial cancer in Sweden

Objective Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective. Materials and methods A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted. Results Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76). Limitations Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment’s cost effectiveness in different countries. Conclusions This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Cost-effectiveness of ticagrelor plus aspirin versus aspirin in acute ischaemic stroke or transient ischaemic attack: an economic evaluation of the THALES trial

ObjectiveTHALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS)...

Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease with a history of PCI: an economic evaluation of THEMIS-PCI using a Swedish healthcare perpective

Abstract Background The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) evaluated ticagrelor compared to placebo for the prevention of myocardial infarction (MI), stroke and cardiovascular (CV) death in 19 220 patients with type 2 diabetes (T2DM) and stable coronary artery disease (CAD) with no prior myocardial infarction (MI) or stroke. THEMIS-PCI was a pre-specified subgroup of 11 154 patients who had a history of percutaneous coronary intervention (PCI) when entering the study. In THEMIS, ticagrelor reduced CV death, MI or stroke, although with an increase in major bleeding compared to aspirin alone, and there was a significant interaction between a prior history of PCI and the net benefit of ticagrelor. In the THEMIS-PCI population, ticagrelor plus aspirin provided a favourable net clinical benefit with a significant 15% reduction in all-cause death, MI, stroke, fatal bleed, or intracranial haemorrhage. Objective The objective of this analysis was to estimate the cost-effectiveness of ticagrelor for the prevention of CV events based on the results of the THEMIS-PCI population using a lifetime horizon from a Swedish healthcare perspective. Methods A lifetime Markov state transition model was developed with health states aligned to the THEMIS trial endpoints. Health state transitions were informed by parametric survival equations fitted to patient level data from THEMIS-PCI population. Treatment discontinuation rates were informed by the THEMIS-PCI population, with all patients assumed to discontinue treatment with ticagrelor after four years. The incidence of bleeding and dyspnoea were modelled as adverse events. Costs (2019 Euros) and utility data were derived from the published literature and the THEMIS-PCI population, respectively, and discounted at 3.0% annually. Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were conducted to quantify uncertainty of key input parameters. Results Treatment with ticagrelor plus aspirin over four years resulted in estimated Quality Adjusted Life Year (QALY) gains of 0.09 at an incremental cost of €1,891 compared to aspirin alone. The estimated incremental cost-effectiveness ratio (ICER) was €19,959/QALY. PSA indicated that ticagrelor was cost-effective in 93% of simulations using a willingness-to-pay threshold of €47,000/QALY and DSA showed that cost-effectiveness was robust to changes in key input parameters (ICER range: €16,504 to €25,012/QALY). Conclusion Based on the results of the THEMIS trial, dual antiplatelet therapy with ticagrelor plus aspirin is likely to be a cost-effective treatment compared with aspirin alone for the prevention of CV events in patients with T2DM and CAD with a history of PCI. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Cost-Effectiveness Analysis of Patiromer in Combination with Renin–Angiotensin–Aldosterone System Inhibitors for Chronic Kidney Disease in Sweden

Patients with chronic kidney disease (CKD) are commonly treated with renin-angiotensin-aldosterone system inhibitors (RAASi) in order to delay progression of renal disease. However, research has shown that RAASi in CKD patients increases hyperkalaemia (HK) prevalence, which leads to RAASi discontinuation or dose reduction with the loss of benefits on the kidney. Patiromer is a novel therapy for HK treatment and may enable patients to remain on their RAASi regimen. This study aimed to assess the cost-effectiveness of patiromer from a Swedish healthcare perspective. A Markov model was developed to evaluate the economic outcomes of patiromer versus no patiromer in HK patients with stage 3-4 CKD taking RAASi. The model consisted of six health states reflecting disease progression and hospitalisations. The analysis mainly considered clinical data from the OPAL-HK trial and national costs. The main outcomes of interest were incremental costs (euro [EUR] 2016) and quality-adjusted life years (QALYs), discounted at 3%, and the incremental cost-effectiveness ratio (ICER). Extensive uncertainty analyses were performed. In comparison to no patiromer, a patiromer patient gained 0.14 QALYs and an incremental cost of EUR 6109 (Swedish krona [SEK] 57,850), yielding an ICER of EUR 43,307 (SEK 410,072)/QALY gained. The results were robust to a range of sensitivity analyses. At a willingness-to-pay threshold of EUR 52,804 (SEK 500,000)/QALY, patiromer had a 50% chance of being cost-effective. The results indicate that patiromer may demonstrate value for money in Swedish patients with stage 3-4 CKD, by enabling RAASi treatment. However, there is a considerable degree of uncertainty.

Costs of Inpatient Rehabilitation for Ischemic Stroke in Patients with Dementia: A Cohort Swedish Register-Based Study.

Background:Stroke and dementia are frequent comorbidities. Dementia possibly increases total costs of stroke care, especially cost of institutionalization and informal medical care. However, stroke rehabilitation costs in dementia patients are understudied.Objective:To estimate inpatient stroke rehabilitation costs for Swedish dementia patients in comparison with non-dementia patients.Methods:A longitudinal cohort study with linked data from the Swedish Dementia Register and the Swedish Stroke Register was conducted. Patients diagnosed with dementia who suffered a first ischemic stroke between 2010 and 2014 (n = 138) were compared with non-dementia patients (n = 935). Cost analyses were conducted from a Swedish health care perspective. The difference of rehabilitation costs between the two groups was examined via simple linear regression (before and after matching by propensity scores of dementia) and multiple linear regression.Results:Mean inpatient rehabilitation costs for dementia and non-dementia patients were SEK 103,693/$11,932 and SEK 130,057/$14,966, respectively (median SEK 92,183/$10,607 and SEK 106,365/$12,239) (p = 0.001). Dementia patients suffered from more comorbidities and experienced lower functioning, compared to non-dementia patients. The inpatient rehabilitation cost for patients with known dementia was 0.84 times the cost in non-dementia individuals.Conclusion:Dementia diagnosis was significantly associated with lower inpatient stroke rehabilitation costs. This might be explained by physicians’ beliefs on the limited effectiveness of rehabilitation in dementia patients. Further research on cost-effectiveness of stroke rehabilitation and patients’ satisfaction with stroke rehabilitation is necessary.

Cost-effectiveness of Pembrolizumab as Second-line Therapy for the Treatment of Locally Advanced or Metastatic Urothelial Carcinoma in Sweden

BackgroundUrothelial carcinoma (UC) is the most common subtype of bladder cancer. The randomized phase 3 KEYNOTE-045 trial showed that pembrolizumab, used as second-line therapy significantly prolonged overall survival with fewer treatment-related adverse events than chemotherapy for advanced UC. Pembrolizumab has been approved by the European Medicines Agency for the treatment of locally advanced or metastatic UC in adults who have received platinum-containing chemotherapy. Many European countries use cost-effectiveness analysis to inform reimbursement decisions. ObjectiveTo assess the cost-effectiveness of pembrolizumab as second-line therapy for the treatment of advanced UC from a Swedish health care perspective. Design, setting, and participantsWe developed a partitioned-survival model to assess the costs and effectiveness of pembrolizumab compared with vinflunine (base case), paclitaxel, or docetaxel monotherapy in patients with advanced UC over a 15-yr time horizon. We obtained Kaplan-Meier estimates for survival endpoints, adverse events, and utility data from KEYNOTE-045. Outcome measurements and statistical analysisWe performed parametric extrapolations to estimate overall and progression-free survival beyond the clinical trial period. Swedish costs and utility weights were used to estimate total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). We performed deterministic and probabilistic sensitivity analyses to assess the robustness of the model results. Results and limitationsIn the base-case analysis, pembrolizumab resulted in a mean survival gain of 1.66 years (1.38 QALYs) at an incremental cost of €69852 and an ICER of €50529/QALY gained versus vinflunine monotherapy. ICERs for other chemotherapies were €81356/QALY for pembrolizumab versus paclitaxel or docetaxel monotherapy, and €71924/QALY for pembrolizumab versus paclitaxel, docetaxel, or vinflunine monotherapy. Long-term follow-up from KEYNOTE-045 and real-world data are needed to validate the extrapolations. ConclusionsThe results indicate that pembrolizumab improves survival, increases QALYs, and is cost-effective as second-line therapy at a willingness-to-pay threshold of €100000/QALY for the treatment of advanced UC. Patient summaryTo date, pembrolizumab is the only treatment associated with a significant overall survival benefit compared with chemotherapy in a randomized controlled trial as second-line therapy for advanced urothelial carcinoma. Our trial-based cost-effectiveness analysis suggests that pembrolizumab is a cost-effective option over chemotherapy in patients with advanced urothelial carcinoma after platinum-based therapy in Sweden.

PUK17 - A COST-EFFECTIVENESS ANALYSIS OF RAASI – ENABLING PATIROMER FOR THE TREATMENT OF HYPERKALEMIA IN SWEDEN

Use of renin-angiotensin aldosterone inhibitors (RAASi) in patients with chronic kidney disease (CKD) reduces the risk of kidney failure and cardiovascular events. However, RAASi induce hyperkalemia (HK), which can result in reduction or discontinuation of RAASi dose and thus comprising the clinical and pharmacoeconomic benefits of RAASi. HK is associated with life-threatening cardiac arrhythmias and a significant economic burden driven by hospitalization. Patiromer is a novel therapy indicated for the treatment of HK, with the potential to enable concomitant RAASi treatment. This study aims to assess the cost-effectiveness of patiromer versus no patiromer in HK patients with CKD stages 3-4 on RAASi in Sweden. Patiromer is reimbursed in Sweden since May 2018. A previously developed Markov model was updated to evaluate the costs and effects of treatment with patiromer versus no patiromer in patients who continued or discontinued RAASi treatment following HK. The model consisted of six mutually exclusive health states reflecting disease progression and associated hospitalization events. The analysis was performed from a Swedish healthcare perspective, using a 3% discount rate. Clinical data were taken from the OPAL-HK trial and from published literature. The main outcomes of interest were incremental costs and quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Extensive sensitivity analyses were performed to assess the robustness of the obtained results. Patiromer compared to no patiromer resulted in 0.14 QALYs gained at an incremental cost of SEK 57,850, yielding an ICER of SEK 410,072 per QALY. The results were robust to a range of sensitivity analyses. At a willingness-to-pay threshold of SEK 500,000/QALY, patiromer had a 50% chance of being cost-effective compared to no patiromer. By enabling RAASi treatment, the results indicate that patiromer is potentially a cost-effective intervention for the treatment of HK in patients with CKD stages 3-4 in Sweden.

The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin.Methods: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID.Results: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters.Limitations: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios.Conclusions: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.

Cost-Effectiveness of Secukinumab Compared to Ustekinumab In Patients With Psoriasis From A Swedish Health Care Perspective

Cost-Effectiveness of Secukinumab Compared to Ustekinumab In Patients With Psoriasis From A Swedish Health Care Perspective

PHP178 - Two-Part Pricing For Patent Protected Medicines †“An Economic Analysis From A Swedish Health Care Perspective

PHP178 - Two-Part Pricing For Patent Protected Medicines †“An Economic Analysis From A Swedish Health Care Perspective

Improvement in COPD management by access to asthma/COPD clinics in primary care: Data from the observational PATHOS study

Chronic obstructive pulmonary disease (COPD) guidelines emphasize the importance of patient education to improve quality of life and avoid exacerbations. Longitudinal evaluations of structured management of COPD in primary care are lacking. To evaluate the impact of primary care asthma/COPD clinics on exacerbations, hospitalizations, and associated costs in COPD. This population-based, retrospective, observational study, linking primary care medical records data to mandatory Swedish national registries, included patients with COPD from 76 primary healthcare centers (1999-2009). A questionnaire on access to an asthma/COPD clinic was retrospectively answered. Propensity score matching was performed at index (COPD diagnosis) by center type (with and without an asthma/COPD clinic). Poisson regression was used to compare the yearly rate of exacerbations (hospitalization, emergency visits, or prescription for oral steroids or antibiotics) and COPD-related prescriptions at the centers. An economic analysis was performed from the Swedish healthcare perspective using 2011 unit costs and the incremental cost-effectiveness ratio was calculated. The study included 21,361 patients (mean age, 68.0 years; 53% female). Access to asthma/COPD clinics increased from 34% to 85% during the study period. Patients at primary healthcare centers with asthma/COPD clinics had 27% fewer exacerbations (0.71 vs. 0.98) and 37% fewer hospitalizations annually (0.36 vs. 0.58) (p<0.0001). Asthma/COPD clinics reduced the annual cost of medication and healthcare contacts by 37% (SEK 52,892 [€5858] to SEK 33,410 [€3700] per patient). Patients at primary healthcare centers with asthma/COPD clinics experienced fewer COPD exacerbations and hospitalizations, and overall treatment costs were substantially reduced. ClinicalTrials.gov identifier: NCT01146392.

A cost-utility study of the use of pregabalin added to usual care in refractory neuropathic pain patients in a Swedish setting

Objectives:Patients refractory to older therapies for neuropathic pain (NeP) have few remaining therapeutic options. This study evaluates the cost-utility of pregabalin in the treatment of patients with refractory neuropathic pain in Sweden, from a healthcare and a societal perspective.Study limitations:The use of non-randomized (observational) data to determine the effectiveness of treatments for NeP. The use of non-Swedish data for some input parameters in the model.Methods:A previously constructed discrete event simulation model was adapted to compare pregabalin combined with usual care to usual care alone in a Swedish setting. Pain profiles were generated using clinical data from five non-randomized pregabalin studies in refractory NeP patients. Utility data were generated from a UK survey of patients with NeP. Cost data were generated from the Swedish Dental and Pharmaceutical Benefits Board (TLV’s) product price database, a national NeP register, and a regional registry study. Indirect costs were estimated from published sources. One-way and probabilistic sensitivity analyses evaluated uncertainty in the model’s output.Results:The incremental cost-effectiveness ratio (ICER) for pregabalin plus usual care treatment compared to usual care was 51,616 SEK/€5364 and 123,993 SEK/€12,886 with and without indirect costs, respectively. One-way sensitivity analyses confirmed the clinical input data as the main driver of the model; even considerable changes to all other input parameters had only a modest effect on the ICER. The ICER remained well below a conservative threshold of 347,495 SEK /€36,113/£30,000 in all scenarios modelled.Conclusions:This study found pregabalin combined with usual care to be cost-effective compared to usual care in patients with refractory NeP from a Swedish Health Care perspective. Moreover, sensitivity analysis showed pregabalin’s cost-effectiveness to be robust in all scenarios modelled.

Cost‐effectiveness of clean air administered to the breathing zone in allergic asthma

Airsonett Airshower (AA) is a novel non-pharmaceutical treatment for patients with perennial allergic asthma that uses a laminar airflow directed to the breathing zone of patients during sleep. It has been shown that AA treatment in addition to optimized standard therapy significantly increases asthma-related quality of life among adolescent asthmatics. However, the cost-effectiveness of AA treatment has not yet been assessed. As reimbursement decisions are increasingly guided by results from the cost-effectiveness analysis, such information is valuable for health-care policy-makers. The objective of this study was to estimate the cost-effectiveness of adding AA treatment with allergen-free air during night sleep to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo. A probabilistic Markov model was developed to estimate costs and health outcomes over a 5-year period. Costs and effects are presented from a Swedish health-care perspective (QALYs). The main outcome of interest was cost per QALY gained. The Airshower strategy resulted in a mean gain of 0.25 QALYs per patient, thus yielding a cost per QALY gained of under euro35 000 as long as the cost of Airshower is below euro8200. Adding AA treatment to optimized standard therapy for adolescents with perennial allergic asthma compared with placebo is generating additional QALYs at a reasonable cost. However, further studies taking more detailed resource use and events such as exacerbations into account would be needed to fully evaluate the cost-effectiveness of AA treatment.

The Cost Effectiveness of Orlistat in a 1-Year Weight-Management Programme for Treating Overweight and Obese Patients in Sweden

To calculate the cost effectiveness (from the Swedish healthcare perspective) of orlistat plus diet for an obese and overweight population in a 1-year weight-management responder programme versus a 1-year weight-management programme based on diet only. As a reference, orlistat plus diet and diet only were also compared with a no-diet alternative. Costs and effectiveness were calculated in a decision-tree model by means of Monte Carlo simulation. Efficacy was derived from a pooled analysis of the orlistat clinical trial programme. Acquisition costs for orlistat (euro, 2003 prices), healthcare costs for visits to doctors and dieticians related to weight management, and costs related to the difference in diabetes mellitus incidence between treatment arms were included in the analysis. The health benefit of temporary weight loss was measured in the number of quality-adjusted life-years (QALYs) gained. The number of responding (those with >5% weight loss) patients at month 3 was almost twice as high with orlistat compared with diet only: 48.9% versus 26.3%. Responding orlistat patients had a weight loss of 15.5% at month 12 compared with 7.9% for all patients on diet only. The incremental cost-effectiveness ratio (ICER) per QALY gained versus diet only was estimated to be 13,125 euro for the average patient starting on orlistat. When orlistat was compared with no diet, the cost effectiveness was improved. However, comparing diet only with no diet gave a slightly higher ICER, indicating that orlistat had an extended dominance over the diet-only alternative. Our estimates indicated that orlistat in a 12-month dietary responder programme increased the number of QALYs and reduced the cumulative incidence of diabetes compared with diet only. Patients starting on orlistat in addition to a dietary programme achieved an ICER that was similar to many other well accepted healthcare treatment programmes. In order to improve the precision of our calculations, we need to confirm the key assumptions regarding temporary weight loss and utility gains, and the relationship between temporary weight loss and diabetes, as well as other co-morbidities, and to have better knowledge of the long-term impact of weight-management programmes in clinical practice, such as changes in weight-controlling behaviours and sustainability of weight loss.

Cost-Effectiveness Analysis of Salmeterol/Fluticasone Propionate 50/500??g vs Fluticasone Propionate 500??g in Patients with Corticosteroid-Dependent Asthma V: Results

Methods: An economic analysis was performed to compare the cost effectiveness of a new formulation combining salmeterol 50μg and fluticasone propionate 500μg in a multidose dry powder (Diskus™) inhaler (n = 167) with that of fluticasone propionate (FP) 500μg (n = 165) also delivered via the Diskus™ in patients with corticosteroid-dependent asthma. Clinical data were obtained from a recent European multicentre trial; the economic analysis adopted a Swedish healthcare perspective. Results: The salmeterol/fluticasone propionate combination (SFC) produced a significantly higher proportion of successfully treated weeks, defined as a ≥5% improvement in percentage predicted peak expiratory flow, than FP alone (57.5 vs 33.6%; p = 0.001). The proportions of symptom-free days (40.2 vs 30.4%; p = 0.012) and episode-free days (30.3 vs 24.9%; p = 0.068) were also higher in the SFC group. Despite the higher drug costs for SFC, the cost per successfully treated week was lower for SFC than for FP alone [SEK365.1 ($US44.30) vs SEK487.8 ($US59.18)]. The incremental cost-effectiveness ratio was SEK192.1 ($US23.31) [95% confidence interval: 58.3, 436.7]. Sensitivity analyses indicated that these results were stable over a range of assumptions. Conclusion: In summary, the new inhaler containing a combination of salmeterol 50μg and FP 500μg led to an increase in healthcare costs but was considerably more effective than FP 500μg alone in patients with corticosteroid-dependent asthma. Despite the additional costs of asthma management, the range of additional benefits suggests that SFC may be a cost-effective treatment option.