Cost-effectiveness and cost-utility analysis of somatrogon once-weekly injections vs. daily growth hormone injection for treating paediatric growth hormone deficiency in Ireland.

OBJECTIVES: Paediatric growth hormone deficiency (pGHD) manifests as growth failure associated with inadequate growth hormone (GH) production. Daily injections of recombinant human GH (dGH) [somatropin] is the current standard of care, which has been shown to be well tolerated and effective, but associated with suboptimal adherence, leading to reduced effectiveness. Somatrogon, a once-weekly injectable long-acting human GH, has demonstrated clinical non-inferiority and significantly lower life interference (i.e. treatment burden) vs. somatropin in two Phase 3 studies. This work evaluated cost-effectiveness and cost-utility of somatrogon vs dGHs from an Irish payer perspective. METHODS: A Markov model was developed for patients starting somatrogon or dGHs treatment at 3-12 years and continuing up to achievement of near adult height (NAH), with growth driven by trial-based height velocity (HV) and treatment-specific adherence. Patients could discontinue treatment at the end of Year 1 (4%). DGH adherence (95.3%-65% over treatment duration) and adherence-growth relationship were based on published evidence. Higher Year 1 adherence of 4%, tapering over time, for somatrogon vs. dGHs was based on clinical consultation. Treatment costs, monitoring costs and costs due to different wastage types (device setting and adherence) were sourced from local data. Health utilities based on height and injection frequency were derived from published literature. Scenario analysis, deterministic and probabilistic sensitivity analysis were performed. RESULTS: Somatrogon treatment led to 1.87-3.66 cm greater NAH gain and 0.21-0.50 higher quality adjusted life years (QALYs) vs. dGHs, across the base case and scenarios evaluated. Somatrogon treatment was associated with cost savings of €5,699-€21,974 and lower cost per cm gained vs. dGHs (€197-€527), per patient. Somatrogon was cost-effective vs. dGHs, with the result consistent across the sensitivity analyses conducted. CONCLUSION: Somatrogon weekly injections were estimated to result in higher NAH, higher QALYs, lower overall costs and lower costs per cm gained than dGHs, in pGHD.

Ceftaroline Fosamil for the Empiric Treatment of Hospitalized Adults with cSSTI: An Economic Analysis from the Perspective of the Spanish National Health System.

Purpose: Complicated skin and soft tissue infections (cSSTI) are associated with high healthcare resource use and costs. The emergency nature of cSSTI hospitalizations requires starting immediate empiric intravenous (IV) antibiotic treatment, making the appropriate choice of initial antibiotic therapy crucial. Patients and Methods: The use of ceftaroline fosamil (CFT) as an alternative to other IV antibiotic therapies for the empiric treatment of hospitalized adults with cSSTI (vancomycin, linezolid, daptomycin, cloxacillin, tedizolid) was evaluated through cost consequences analysis. The model structure was a decision tree accounting for four different pathways: patients demonstrating early response (ER) either discharged early (with oral antibiotic) or remaining in hospital to continue the initial therapy; non-responders either remaining on the initial IV therapy or switching to a second-line antibiotic. The model perspective was the Spanish National Health System. Results: CFT resulted in average percentage of patients discharged early (PDE) of 24.6% (CI 19.49-30.2%) with average total cost per patient of €6763 (€6268-€7219). Vancomycin, linezolid, daptomycin and tedizolid resulted in average PDE of 22% (17.34-27.09%), 26.4% (20.5-32.32%), 28.6% (22.08-35.79%) and 26.5% (20.39-33.25%), respectively, for a total cost per patient of €6,619 (€5,902-€6,929), €6,394 (€5,881-€6,904), €6,855 (€5,800-€7,410) and €7,173 (€6,608-€7,763), respectively. Key model drivers were ER and antibiotic treatment duration, with hospital costs accounting for over 83% of the total expenditures. Conclusion: Given its clinical and safety profile, CFT is an acceptable choice for cSSTI empiric therapy providing comparable ER and costs to other relevant antibiotic options.

Cost-effectiveness analysis of apixaban versus vitamin K antagonists for antithrombotic therapy in patients with atrial fibrillation after acute coronary syndrome or percutaneous coronary intervention in Spain.

BACKGROUND/OBJECTIVE: AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI. METHODS: A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%. RESULTS: Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, -13.9 and -1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA. CONCLUSIONS: Apixaban was a dominant treatment strategy than VKA from both the Spanish payer's and societal perspectives, regardless of treatment strategy considered.

Impact of coronary artery disease on contractile function and ventricular-arterial coupling during exercise: Simultaneous assessment of left-ventricular pressure-volume and coronary pressure and flow during cardiac catheterization.

Coronary artery disease (CAD) can adversely affect left ventricular (LV) performance during exercise by impairment of contractile function in the presence of increasing afterload. By performing invasive measures of LV pressure-volume and coronary pressure and flow during exercise, we sought to accurately measure this with comparison to the control group. Sixteen patients, with CCS class >II angina and CAD underwent invasive simultaneous measurement of left ventricular pressure-volume and coronary pressure and flow velocity during cardiac catheterization. Measurements performed at rest were compared with peak exercise using bicycle ergometry. The LV contractile function was measured invasively using the end-systolic pressure-volume relationship, a load independent marker of contractile function (Ees). Vascular afterload forces were derived from the ratio of LV end-systolic pressure to stroke volume to generate arterial elastance (Ea). These were combined to assess cardiovascular performance (ventricular-arterial [VA] coupling ratio [Ea/Ees]). Eleven patients demonstrated flow-limiting (FL) CAD (hyperemic Pd/Pa <0.80; ST-segment depression on exercise); five patients without flow-limiting (NFL) CAD served as the control group. Exercise in the presence of FL CAD was associated impairment of Ees, increased Ea, and deterioration of VA coupling. In the control cohort, exercise was associated with increased Ees and improved VA coupling. The backward compression wave energy directly correlated with the magnitude contraction as measured by dP/dTmax (r = 0.88, p = 0.004). This study demonstrates that in the presence of flow-limiting CAD, exercise to maximal effort can lead to impairment of LV contractile function and a deterioration in VA coupling compared to a control cohort.

Economic analysis of ceftaroline fosamil for treating community-acquired pneumonia in Spain.

Background: Adults admitted to hospital with community-acquired pneumonia (CAP) impose significant burden upon limited hospital resources. To achieve early response and possibly early discharge, thus reducing hospital expenditure, the choice of initial antibiotic therapy is pivotal.Methods: A cost-consequences model was developed to evaluate ceftaroline fosamil (CFT) as an alternative to other antibiotic therapies (ceftriaxone, co-amoxiclav, moxifloxacin, levofloxacin) for the empiric treatment of hospitalized adults with moderate/severe CAP (PORT score III-IV) from the perspective of the Spanish National Health System (NHS).Findings: Compared with ceftriaxone, the model predicted an increase in the number of CFT-treated patients discharged early (PDE) (30.6% vs. 26.1%) while decreasing initial antibiotic failures (3.8% vs. 7.6%). For patients with pneumococcal pneumonia, CFT was cost-saving vs. ceftriaxone (by 1.2%) and significantly increased PDE (32.1% vs. 24.6%). CFT resulted in cost-saving vs. levofloxacin, due lower initial antibiotic therapy costs and increased PDE (30.6% vs. 14.9%). Moxifloxacin and co-amoxiclav early response rate of 53.63% and 54.24% resulted in cost neutrality vs. CFT, with direct comparison hampered by the significantly different early response criteria utilized in the literature.Conclusions: Despite a higher unit cost, CFT is a reasonable alternative to other agents for adults hospitalized with moderate/severe CAP, given the projected higher PDE achieved with similar or lower total costs.

In vivo strain assessment of the abdominal aortic aneurysm.

The only criteria currently used to inform surgical decision for abdominal aortic aneurysms are maximum diameter (>5.5 cm) and rate of growth, even though several studies have identified the need for more specific indicators of risk. Patient-specific biomechanical variables likely to affect rupture risk would be a valuable addition to the science of understanding rupture risk and prove to be a life saving benefit for patients. Local deformability of the aorta is related to the local mechanical properties of the wall and may provide indication on the state of weakening of the wall tissue. We propose a 3D image-based approach to compute aortic wall strain maps in vivo. The method is applicable to a variety of imaging modalities that provide sequential images at different phases in the cardiac cycle. We applied the method to a series of abdominal aneurysms imaged using cine-MRI obtaining strain maps at different phases in the cardiac cycle. These maps could be used to evaluate the distensibility of an aneurysm at baseline and at different follow-up times and provide an additional index to clinicians to facilitate decisions on the best course of action for a specific patient.