Background Obesity and overweight are major risk factors for several chronic diseases. There is limited systematic evaluation of risk equations that predict the likelihood of developing an obesity or overweight associated complication. Predicting future risk is essential for health economic modelling. Availability of future treatments rests upon a model’s ability to inform clinical and decision-making bodies.  This systematic literature review aimed to identify studies reporting (1) equations that calculate the risk for individuals with obesity, or overweight with a weight-related complication (OWRC), of developing additional complications, namely T2D, cardiovascular (CV) disease (CVD), acute coronary syndrome, stroke, musculoskeletal disorders, knee replacement/arthroplasty, or obstructive sleep apnea; (2) absolute or proportional risk for individuals with severe obesity, obesity or OWRC developing T2D, a CV event or mortality from knee surgery, stroke, or an acute CV event. Methods Databases (MEDLINE and Embase) were searched for English language reports of population-based cohort analyses or large-scale studies in Australia, Canada, Europe, the UK, and the USA between January 1, 2011, and March 29, 2021. Included reports were quality assessed using an adapted version of the Newcastle Ottawa Scale. Results Of the 60 included studies, the majority used European cohorts. Twenty-nine reported a risk prediction equation for developing an additional complication. The most common risk prediction equations were logistic regression models that did not differentiate between body mass index (BMI) groups (particularly above 40 kg/m2) and lacked external validation. The remaining included studies (31 studies) reported the absolute or proportional risk of mortality (29 studies), or the risk of developing T2D in a population with obesity and with prediabetes or normal glucose tolerance (NGT) (three studies), or a CV event in populations with severe obesity with NGT or T2D (three studies). Most reported proportional risk, predominantly a hazard ratio. Conclusion More work is needed to develop and validate these risk equations, specifically in non-European cohorts and that distinguish between BMI class II and III obesity. New data or adjustment of the current risk equations by calibration would allow for more accurate decision making at an individual and population level.

Aims To evaluate the short‐term cost‐effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia. Materials and methods A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality‐adjusted life years [QALYs]) with degludec vs glargine U100 over a 2‐year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors. Results In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non‐fatal myocardial infarction, non‐fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes. Conclusion Over a 2‐year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.

No abstract

Introduction: Congenital hemophilia B is a rare blood disorder, caused by mutations in the F9 gene that lead to dysfunctional, reduced, or no clotting factor IX (FIX), resulting in prolonged bleeding episodes and in severe cases, spontaneous bleeding episodes. Maintaining sufficient FIX activity in the bloodstream through routine prophylactic administration of FIX, is the standard of care for prevention of bleeds in hemophilia B patients in Canada. Breakthrough bleeding (BTB) episodes are treated acutely with additional doses of FIX. In Canada, real-world data for patients with hemophilia B, including clinical outcomes and consumption rates of FIX, are recorded in the Canadian Bleeding Disorders Registry (CBDR). FIX products for patients with hemophilia B are subject to national competitive procurement processes administered by the Canadian Blood Service (CBS) and Héma-Québec. Nonacog beta pegol (N9-GP), an extended half-life (EHL) recombinant FIX concentrate, was recently awarded a CBS contract and subsequently made available across Canada (except Québec) from April 1, 2018 to adult patients. For those patients already on another EHL FIX treatment, a forced switch to N9-GP occurred. The objective of the present study was to estimate the impact on treatment costs of switching from a prior FIX to N9-GP, based on real-world annualized bleed rates (ABRs) and FIX consumption volumes (pre- and post-N9-GP switch) for patients on prophylaxis with their previous treatment and N9-GP, as recorded in the CBDR as of 30 September 2019. Methods: Real-world data from the CBDR for FIX consumption and ABR were used to inform a cost consequence model, developed in Microsoft Excel. Only patients for whom data existed in the CBDR for 6-months pre-switch to N9-GP and who had received ≥3 months of N9-GP treatment were included. Since April 2018, N9-GP replaced eftrenonacog alfa as the EHL product available to adult patients covered by CBS, while nonacog alfa continued to be the recombinant standard half-life (SHL) product available. Based on this, it was assumed that the EHL to N9-GP switches were from eftrenonacog alfa and the SHL switches are from nonacog alfa. For comparison of N9-GP with nonacog alfa and eftrenonacog alfa, treatment of adult males (assumed body weight of 70 kg) with severe hemophilia B was modeled over a 1-year time horizon. Since the competitive procurement process used in Canada results in confidential per-unit FIX prices, a price from a similar market was used for assessment of the cost impact. The German market was selected because all recombinant FIX products available in Canada are reimbursed in Germany. Converting the German per-IU prices, as published in the Lauer-Taxe®, using the Bank of Canada average exchange rate for the previous year, resulted in a price of CAD $2.54, $1.50 and $2.18 per IU for N9-GP, nonacog alfa, and eftrenonacog alfa, respectively. Real-world annualized mean FIX consumption volumes for prophylaxis, per BTB and real-world mean total ABRs for each product were then multiplied by the price per IU for each FIX product to derive estimates of real-world annual treatment costs associated with the use of nonacog alfa and eftrenonacog alfa (pre-switch), and N9-GP (post-switch). Results: Real-world annual prophylaxis consumption volumes, as reported in the CBDR, were reduced following treatment switch to N9-GP (Table 1). The switch to N9-GP was associated with improved ABRs, from 7.38 to 2.56 and 4.76 to 2.68 for patients on prior treatment with nonacog alfa and eftrenonacog alfa, respectively. Comparative treatment costs (for prophylaxis and BTB) based on real-world data were reduced from $643,400 to $412,700 when switching from nonacog alfa to N9-GP and from $486,938 to $358,822 when switching from eftrenonacog alfa to N9-GP. Treatment with N9-GP was therefore associated with a 35.8% and 26.3% reduction in costs following a switch from nonacog alfa, and eftrenonacog alfa, respectively. Conclusion: Real-world FIX consumption and bleeding outcomes data demonstrate that N9-GP is cost-saving compared with nonacog alfa and eftrenonacog alfa (assuming per-IU prices based on German costs converted to Canadian dollars) while also achieving a reduction in ABR, regardless of whether patients previously received an SHL or EHL FIX product. N9-GP can therefore be considered a dominant treatment option compared with nonacog alfa and eftrenonacog alfa for the treatment of hemophilia B. Disclosures MacDonald: Novo Nordisk Canada Inc: Current Employment. Lee:Novo Nordisk A/S: Current Employment. Caillaud:Novo Nordisk Canada Inc: Current Employment. Luckevich:Novo Nordisk Canada Inc.: Current Employment. Bentley:Mtech Access: Consultancy, Other: Consultant for Novo Nordisk.

OBJECTIVES: This study assessed the cost-effectiveness of once-weekly semaglutide 2.4mg injection as adjunct to reduced-calorie meals and increased physical activity (diet and exercise, D&E), in adult patients with obesity (body mass index [BMI] of ≥30 kg/m2) or overweight (BMI 27-30 kg/m2) in the presence of ≥1 weight-related comorbidity, by comparing it with D&E alone or D&E in combination with liraglutide 3.0mg, orlistat, or naltrexone 32mg/bupropion (NB32). METHODS: The safety and efficacy of semaglutide 2.4mg and D&E were sourced from the STEP 1 and STEP 2 trials, while a network meta-analysis informed the relative efficacy vs. other comparators. The Core Obesity Model was used to extrapolate costs and health outcomes (both discounted at 1.5% annually) over 40 years for a cohort with starting age 50 years and starting BMI 37.5 kg/m2, taking D&E alone or in combination with other pharmacotherapies for 1 year. Costs were analyzed from a societal perspective, including publicly and privately funded health expenses, patient co-payments, and indirect costs. RESULTS: Semaglutide 2.4mg reduced weight and reverted prediabetes prevalence more than alternative therapies. This translated into delays in the occurrence of weight-related complications, and gains in life-expectancy between 0.081 years vs. D&E (maximum gain) and 0.030 years vs. liraglutide 3.0mg (minimum gain), and quality-adjusted life-years (QALYs) between 0.103 vs. D&E and 0.039 vs. liraglutide 3.0mg, at additional costs. The incremental cost-utility ratios were 29,677 Canadian dollars (CAD)/QALY gained vs. D&E, CAD12,369/QALY gained vs. liraglutide 3.0mg, CAD25,663/QALY gained vs. orlistat and CAD25,003/QALY gained vs. NB32. The cost-effectiveness acceptability curve showed a high likelihood of subcutaneous semaglutide 2.4 mg injection being considered cost-effective, at willingness-to-pay thresholds of CAD50,000/QALY and beyond. CONCLUSION: Based on this analysis, the use of semaglutide 2.4mg injection can be considered a cost-effective alternative compared with D&E alone, or D&E in combination with other pharmacotherapies.