Comparative efficacy of delafloxacin for complicated and acute bacterial skin and skin structure infections: results from a network meta-analysis.

BACKGROUND: Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI. METHODS: A systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE®, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid. RESULTS: A feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation. CONCLUSIONS: Delafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.

Calibration of the IQVIA Core Diabetes Model to the stroke outcomes from the SUSTAIN 6 cardiovascular outcomes trial of once-weekly semaglutide.

AIMS: In the SUSTAIN 6 cardiovascular outcomes trial, once-weekly semaglutide was associated with a statistically significant reduction in major adverse cardiovascular events compared with placebo. To date, no studies have assessed how accurately existing diabetes models predict the outcomes observed in SUSTAIN 6. The aims of this analysis were to investigate the performance of the IQVIA Core Diabetes Model when used to predict the SUSTAIN 6 trial outcomes, to calibrate the model such that projected outcomes reflected observed outcomes, and to examine the impact of calibration on the cost-effectiveness of once-weekly semaglutide from a UK healthcare payer perspective. METHODS: The IQVIA Core Diabetes Model was calibrated to ensure that the projected non-fatal stroke event rates reflected the non-fatal stroke event rates observed in SUSTAIN 6 over a two-year time horizon. Cost-effectiveness analyses of once-weekly semaglutide versus placebo plus standard of care were conducted over a lifetime horizon using the uncalibrated and calibrated models to assess the impact on cost-effectiveness outcomes. RESULTS: To replicate the non-fatal stroke event rate in SUSTAIN 6, calibration of the model through the application of relative risks for stroke of 1.07 and 1.65 with once-weekly semaglutide and placebo, respectively, was required. In the long-term cost-effectiveness analysis, the uncalibrated model projected an incremental cost-effectiveness ratio for once-weekly semaglutide versus placebo plus standard of care of GBP 22,262 per quality-adjusted life year (QALY) gained, which fell to GBP 17,594 per QALY gained when the calibrated model was used. CONCLUSIONS: The requirement for calibration to replicate the outcomes observed in SUSTAIN 6 suggests that the reductions in risk of cardiovascular complications observed with once-weekly semaglutide cannot be solely explained by differences in conventional risk factors. Accurate estimation of the risk of diabetes-related complications using methods such as calibration is important to ensure accurate cost-effectiveness analyses are conducted.

Cost-minimisation analysis of oritavancin for the treatment of acute bacterial skin and skin structure infections from a United Kingdom perspective.

BACKGROUND: Early discharge (ED) from hospital and outpatient parenteral antibiotic therapy (OPAT) are effective approaches for the management of a range of infections, including acute bacterial skin and skin structure infections (ABSSSI). Strategies that facilitate ED, thereby reducing complications such as healthcare-acquired infection whilst enhancing patient quality of life, are being increasingly adopted in line with good antimicrobial stewardship practice. This study presents a cost-minimisation analysis for the use of oritavancin at ED versus relevant comparators from a National Health Service (NHS) and personal and social services United Kingdom perspective. METHODS: A cost-minimisation model considering adult patients with ABSSSI with suspected or confirmed methicillin-resistant Staphylococcus aureus (MRSA) infection, was developed based on publicly available NHS costs, practice guidelines for ABSSSI and clinical expert's opinion. Cost of treatment and treatment days were compared for oritavancin at ED to dalbavancin, teicoplanin, daptomycin and linezolid. RESULTS: Following the empiric use of either flucloxacillin or vancomycin in the inpatient setting, oritavancin was compared to OPAT with dalbavancin, teicoplanin and daptomycin, and oral linezolid from day 4 of treatment. Oritavancin at ED reduced treatment duration by 0.8 days and led to cost savings of £281 in comparison to dalbavancin. In comparison to teicoplanin, daptomycin and linezolid, oritavancin reduced treatment duration by 5 days, with marginally higher costs (£446, £137, and £1,434, respectively). CONCLUSION: Oritavancin, used to support ED, is associated with lower costs compared with dalbavancin and reduced treatment duration relative to all comparators. Its use would support an ED approach in MRSA ABSSSI management.

Cost-effectiveness analysis of vaborem for the treatment of carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniae carbapenemase (CRE-KPC) infections in the UK.

OBJECTIVE: The study objective of this analysis was to determine the cost-effectiveness of vaborem (meropenem-vaborbactam) compared to the best available therapy (BAT) in adult patients with carbapenem-resistant Enterobacteriaceae-Klebsiella pneumoniae carbapenemase (CRE-KPC) infections from the perspective of the UK National Health Service (NHS) and Personal Social Services (PSS). METHODS: A decision tree model was developed to conduct a cost-effectiveness analysis for Vaborem compared to BAT in CRE-KPC patients over a 5 year time horizon. The model structure for Vaborem simulated the clinical pathway of patients with a confirmed CRE-KPC infection. Model inputs for clinical effectiveness were sourced from the TANGO II trial, and published literature. Costs, resource use and utility values associated with CRE-KPC infections in the UK were sourced from the British National Formulary, NHS reference costs and published sources. RESULTS: Over a 5 year time horizon, Vaborem use increased total costs by £5165 and increased quality-adjusted life years (QALYs) by 0.366, resulting in an incremental cost-effectiveness ratio (ICER) of £14,113 per QALY gained. The ICER was most sensitive to the probability of discharge to long-term care (LTC), the annual cost of LTC and the utility of discharge to home. At thresholds of £20,000/QALY and £30,000/QALY, the probability of Vaborem being cost-effective compared to BAT was 79.85% and 94.93%, respectively. CONCLUSION: Due to a limited cost impact and increase in patient quality of life, vaborem can be considered as a cost-effective treatment option compared to BAT for adult patients with CRE-KPC infections in the UK.

Cost-effectiveness analysis of recombinant human follicle-stimulating hormone alfa(r-hFSH) and urinary highly purified menopausal gonadotropin (hMG) based on data from a large German registry.

This was a retrospective real-world evidence analysis of the costs per live birth for reference recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG-HP), based on data from a German in vitro fertilization registry (RecDate). Pregnancy and live birth rates from the RecDate real-world evidence study over three complete assisted reproductive technology (ART) cycles using the same gonadotropin drug were used as clinical inputs. Costs related to ART treatment and to drugs were obtained from public sources. Treatment with r-hFSH-alfa resulted in higher adjusted cumulative live birth rates versus hMG-HP after one (25.3% vs. 22.3%), two (30.9% vs. 27.5%), and three (31.9% vs. 28.6%) ART cycles. Costs per live birth were lower with r-hFSH-alfa versus hMG-HP after one (€17,938 vs. €20,054), two (€18,251 vs. €20,437), and three (€18,473 vs. €20,680) ART cycles. r-hFSH-alfa was found to be a cost-effective strategy compared with hMG-HP over three cycles.

Originator recombinant human follitropin alfa versus recombinant human follitropin alfa biosimilars in Spain: A cost-effectiveness analysis of assisted reproductive technology related to fresh embryo transfers.

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al. [4]. Cost inputs were extracted from publicly available Spanish sources. The costs per live birth were lower with originator r-hFSH-alfa (€18,138) versus r-hFSH-alfa biosimilars (€20,377). The incremental cost-effectiveness ratio was €7208 for originator r-hFSH-alfa versus biosimilars. Drug acquisition costs for originator r-hFSH-alfa represented 10.5% of total costs in the base case analysis, and 6.2% in a treatment cycle resulting in live birth with one fresh embryo transfer. Results from the sensitivity analyses confirmed the robustness of the findings.

Cost-Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus Suboptimally Controlled on Basal Insulin Plus Metformin in the UK.

INTRODUCTION: A cost-effectiveness analysis was conducted comparing a fixed-ratio combination (FRC) of insulin glargine 100 units/mL plus lixisenatide (iGlarLixi) versus the FRC of insulin degludec plus liraglutide (iDegLira) and the free-combination comparators insulin glargine plus dulaglutide (iGlar plus Dula) and basal insulin plus liraglutide (BI plus Lira). METHODS: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for a cohort of patients with type 2 diabetes mellitus (T2DM) from the UK healthcare perspective. Initial clinical data for iGlarLixi were based on the randomized, controlled LixiLan-L trial and the relative treatment effects for comparators were based on an indirect treatment comparison using data from the AWARD-9 (iGlar plus Dula), LIRA ADD2 BASAL (BI plus Lira), and DUAL V (iDegLira) trials. Costs were derived from publicly available sources. Lifetime costs (in British Pound Sterling [£]) and quality-adjusted life-years (QALYs) were predicted; net monetary benefit (NMB) for iGlarLixi versus comparators was derived using a willingness-to-pay threshold of £20,000. Extensive scenario and sensitivity analyses were conducted. RESULTS: Estimated costs were lowest with iGlarLixi (£31,295) compared with iGlar plus Dula (£38,790), iDegLira (£40,179), and BI plus Lira (£42,467). Total QALYs gained were identical with iGlarLixi and iDegLira (8.438), and comparable with iGlar plus Dula (8.439) and BI plus Lira (8.466). NMB for iGlarLixi was positive versus all comparators (£10,603.86 vs. BI plus Lira; £7,466.24 vs. iGlar plus Dula; £8.874.11 vs. iDegLira). CONCLUSION: In patients with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi provides very similar outcomes and substantial cost savings, compared with other fixed and free combinations of insulins plus glucagon-like peptide-1 receptor agonists.

A cost-effectiveness evaluation of the originator follitropin alpha compared to the biosimilars for assisted reproduction in Germany.

Background and objectives: Demand for assisted reproduction technology (ART) in Germany is high, with 100,844 treatment cycles during 2016. Many ART procedures involve ovarian stimulation with follicle stimulating hormone (FSH). Recently, biosimilar FSH products have become available. The objective of this study was to evaluate the cost-effectiveness of the recombinant FSH Gonal-f® (Originator) in comparison to biosimilar follitropin alfa, Bemfola® (Biosimilar 1) and Ovaleap® (Biosimilar 2), from a German payer perspective in terms of cost per live birth. Methods: A decision tree model was developed, based on one cycle of assisted reproduction, to compare the original product to biosimilars. Clinical inputs, including live birth rates and adverse event rates were obtained from published randomized trials. Cost inputs were obtained from publicly available German sources. Clinical inputs, model structure and methodology were based on previous publications and validated by a clinical expert. Results: Results indicated that the live birth rate is higher for the Originator compared to Biosimilar 1 (40.7% vs 32.1% respectively), and Biosimilar 2 (32.2% vs 26.8%). The average cost per live birth for women treated with the Originator was estimated to be lower than those who were treated with biosimilars: Originator vs Biosimilar 1 (€10,510 vs €12,192), Originator vs Biosimilar 2 (€12,590 vs €13,606). The analysis also found that the Originator is associated with an incremental cost-effectiveness of €4,168 and €7,540 per additional live birth versus Biosimilar 1 and Biosimilar 2 respectively. Sensitivity analysis indicated probabilities of pregnancy, embryo transfer and live birth, were key drivers of model costs. Scenario analysis confirmed the robustness of the model outcomes. Conclusion: This study suggests that treatment with the Originator could result in a lower cost per live birth in comparison to biosimilars. Further analysis using real-world data, when available, is recommended to validate the results of the present study.