Cost-effectiveness Analysis of Monoclonal Antibodies in the First-line Treatment of RAS Wild-type Metastatic Colorectal Cancer: A Systematic Review.

PURPOSE: First-line treatment with monoclonal antibodies (bevacizumab, cetuximab, and panitumumab) for RAS wild-type metastatic colorectal cancer (mCRC) has advanced. The costs of drugs targeted to mCRC are high. This systematic review aimed to summarize the cost-effectiveness of monoclonal antibodies in the first-line treatment of RAS wild-type mCRC. METHODS: We searched 5 databases to find original-research cost-effectiveness analyses of monoclonal antibodies used in the first-line treatment of patients with RAS wild-type mCRC. Three reviewers independently evaluated all of the records to be screened. FINDINGS: A total of 15 articles, 12 cost-effectiveness analyses, and 3 cost-utility analyses were identified. The reporting of identified articles was assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 checklist. They were assigned to 1 of 6 categories based on the combination of the intervention and control groups, the most common of which was cetuximab + chemotherapy versus bevacizumab + chemotherapy. The results of the cost-effectiveness analyses may have varied because of the differences in settings, such as country, study population, RAS mutation status, efficacy data, and model structure, in which each study was conducted. IMPLICATIONS: Although treatment with monoclonal antibodies has demonstrated efficacy in terms of life-years gained and progression-free survival, the most cost-effective treatment among monoclonal antibodies remains controversial; however, most of the studies that compared a monoclonal antibody + chemotherapy versus chemotherapy alone reported that chemotherapy alone was a cost-effective strategy. Future studies are needed to evaluate the cost-effectiveness of treating patients with mCRC using biomarker-driven precision medicine.

Analysis of Clinical Efficacy and Adverse Effects of ß-Blocking Agents Used Clinically for Chronic Heart Failure.

Clinical efficacy and adverse effects of the ß-blocking agents, carvedilol, bisoprolol, and metoprolol were analyzed theoretically, and then compared quantitatively, for the purpose of determining their proper use for chronic heart failure. Initially, we evaluated occupancy binding to the ß1 and ß2 receptors (Фssß1 and Фssß2) by these drugs. Thereafter, we examined the relationship between Фssß1 values and left ventricular ejection fraction (LVEF) increase rate to determine efficacy. The result showed that the efficacy with carvedilol could be attained with a lower Фssß1 value than the others. Therefore, we constructed a model under the assumption that ß-blocking agents exert both indirect action of LVEF increase through the ß1 receptor and direct action on ryanodine receptor 2. Using the model, it was suggested that these drugs have no differences in regard to the efficacy, while it was clarified theoretically that only carvedilol produces an effect that directly involves ryanodine receptor 2 at clinical doses. We also investigated decreases in heart rate and forced expiratory volume in 1 s as adverse effects of ß-blocking agents using a ternary complex model. It was indicated that carvedilol is less likely to induce a heart rate decrease. Meanwhile, it was also suggested that the risk of an asthmatic attack was higher for carvedilol at clinical doses. Our results are considered useful for selection of a proper ß-blocking agent and its administration at a reasonable dose for successful heart failure therapy.

Evaluation of clinical bradycardiac effect and respiratory adverse effect of ß-blocking agents in coronary computed tomography angiography based on theoretical analysis.

ß-blocking agents are used for patients with tachycardia to improve the image quality of coronary computed tomography angiography (CCTA). In this study, we analyzed the clinical bradycardiac effects and the adverse respiratory effects of five ß-blocking agents (landiolol, esmolol, propranolol, metoprolol and atenolol) used for CCTA. The changes of the occupancy binding to ß1 or ß2 receptor of these drugs were calculated based on the receptor occupancy theory. Thereafter, we predicted both the rate of heart rate decline (▲HR) as a clinical effect and the rate of decrease in forced expiratory volume in 1 s (▲FEV1) as an adverse effect, by using the ternary complex model. The results showed that the drugs with ▲HR greater than 10 %, necessary for CCTA, were as follows: landiolol at 13.5 %, propranolol at 11.0 %, and atenolol at 22.6 %. The ▲HR values at the end of CCTA for those three drugs were 0.3, 6.7, and 22.9 %, respectively. It is desirable for the bradycardiac effect to disappear at the end of CCTA. Therefore, landiolol is thought to be a preferable drug. On the other hand, ▲FEV1 at start and end of CCTA for those three drugs was 0.04-2.5, 34.9-40.3, and 6.0-6.1 %, respectively. Our results suggested that landiolol has the most appropriate effect and safety for patients with tachycardia who are undergoing a CCTA procedure.

Cost minimization analysis of beta-blocker at the time of CT imaging for suspected of coronary heart disease in Japan.

OBJECTIVES: To conduct a cost-minimization analysis of landiolol for CT diagnosis of coronary heart diseases in patients with tachycardia in Japan. METHODS: A decision-tree model was constructed to analyze costs from the healthcare payer's perspective. Drug costs and diagnosis costs, computer tomography coronary angiography (CTCA), and coronary angiography (CAG), are adopted to the model. Landiolol is administered only to slow the heart rate to take CT images appropriately. Since some trials proved that there was no difference between landiolol and placebo in terms of efficacy and safety, this study conducted cost-minimization analysis. Of those suspected of coronary heart diseases, 22.5% are thought to be taking beta-blockers. The success rates for CT scanning for landiolol and placebo, derived from domestic trial data, were 81.4% (96/118, 77.8-84.9%) and 54.2% (64/118, 49.7-58.8%). Patients who failed to take a CT image were thought to take CAG. The healthcare cost was derived from a Japanese fee schedule. Costs of landiolol, CT imaging, and CAG are JPY2634 (USD1 = JPY100, as of November 20, 2013), JPY38,116, and JPY101,322, respectively. The positive rate for CAG, derived from domestic trial data, was 37.1% (33/89, 32.0-42.2%). Various sensitivity analyses, both univariate and probabilistic ones, were conducted. RESULTS: In the base case analysis, expected costs per patient for landiolol and placebo were JPY78,956 and JPY82,232, respectively. In budget impact analysis, 81,062 patients are eligible for landiolol and it can save JPY266million for whole patients. Sensitivity analyses suggested the robustness of the results. LIMITATIONS: This study did not consider any adverse effects in the decision-tree model. This model was developed especially for measuring the cost-saving effect of landiolol, through decreasing the number of patients who require CAG, due to imaging failure. CONCLUSIONS: Landiolol for CTCA diagnosis in patients suspected of coronary heart disease with tachycardia is thought to be cost saving.