Glucose-lowering treatment patterns in patients with diabetic kidney disease.

OBJECTIVES: Recent trials of glucose-lowering drugs (GLDs) have drawn attention to renal outcomes. Our goal was to understand how patients with diabetic kidney disease (DKD) are treated in general practices in the United States. STUDY DESIGN: Retrospective cohort study using a national-level claims data set and electronic health records. METHODS: Patients (≥ 18 years) with type 2 diabetes, whose estimated glomerular filtration rates (eGFRs) were between 15 and 89 mL/min/1.73 m2 between 2016 and 2018, were selected. Use of different GLDs during a 12-month period was examined across all eGFR levels. RESULTS: Of the 25,486 sample patients, 69.2%, 18.9%, 9.6%, and 2.3% had an eGFR in the ranges of 60 to 89, 45 to 59, 30 to 44, and 15 to 29 mL/min/1.73 m2, respectively. Metformin was used by nearly 33% of patients with an eGFR of 30 to 44 mL/min/1.73 m2 and by 10% of patients with an eGFR less than 30 mL/min/1.73 m2. Less than 10% (across all eGFR levels) of patients used glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors. Use of insulin was more frequent among patients with a lower eGFR (P < .05). The findings were similar in subgroups with different hemoglobin A1c levels (< 7% and ≥ 7%). CONCLUSIONS: Real-world treatment of DKD in the United States is suboptimal. Inappropriate use of some GLD classes, especially in advanced DKD stages, was found along with lower than expected use of modern agents that are considered safe and effective to treat glycemic outcomes. Efforts may be needed to improve understanding of safety, glycemic efficacy, and overall clinical value of GLDs across DKD stages.

Impact of Sustained Weight Loss on Cardiometabolic Outcomes.

Obesity increases the risk of developing type 2 diabetes, hypertension, and hyperlipidemia. We sought to determine the impact of obesity maintenance, weight regain, weight loss maintenance, and magnitudes of weight loss on future risk and time to developing these cardiometabolic conditions. This was a retrospective cohort study of adults receiving primary care at Geisinger Health System between 2001 and 2017. Using electronic health records, patients with ≥3-weight measurements over a 2-year index period were identified and categorized. Obesity maintainers (OM) had obesity (body mass index ≥30 kg/m²) and maintained their weight within ±3% from baseline (reference group). Both weight loss rebounders (WLR) and weight loss maintainers (WLM) had obesity at baseline and lost >5% body weight in year 1; WLR regained ≥20% of weight loss by end of year 2 and WLM maintained ≥80% of weight loss. Incident type 2 diabetes, hypertension, and hyperlipidemia, and time-to-outcome were determined for each study group and by weight loss category for WLM. Of the 63,567 patients included, 67% were OM, 19% were WLR, and 14% were WLM. The mean duration of follow-up was 6.6 years (SD, 3.9). Time until the development of electronic health record-documented type 2 diabetes, hypertension, and hyperlipidemia was longest for WLM and shortest for OM (log-rank test p <0.0001). WLM had the lowest incident type 2 diabetes (adjusted hazard ratio [HR] 0.676 [95% confidence interval [CI] 0.617 to 0.740]; p <0.0001), hypertension (adjusted HR 0.723 [95% CI 0.655 to 0.799]; p <0.0001), and hyperlipidemia (adjusted HR 0.864 [95% CI 0.803 to 0.929]; p <0.0001). WLM with the greatest weight loss (>15%) had a longer time to develop any of the outcomes compared with those with the least amount of weight loss (<7%) (p <0.0001). In an integrated delivery network population, sustained weight loss was associated with a delayed onset of cardiometabolic diseases, particularly with a greater magnitude of weight loss.

Cardiovascular Disease in Patients With Type 2 Diabetes: A Qualitative Analysis of Knowledge, Attitudes, and Beliefs of Health Care Professionals.

Guidelines for the management of patients with type 2 diabetes mellitus (T2DM) recommend SGLT-2 (sodium-glucose cotransporter 2) inhibitors and GLP-1 RAs (glucagon-like peptide 1 receptor agonists) as second-line agents for patients with, or at risk for, cardiovascular disease. A better understanding of guideline implementation will further the provision of evidence-based health care to patients. Interviews and surveys of clinicians were conducted to understand providers' knowledge, attitudes, and beliefs related to the 2019 American Diabetes Association Standards of Care for T2DM. There was a lack of widespread knowledge of the guidelines and comfort with their use. Clinicians require additional training and education on the efficacy of the new medications and accompanying clinical guidelines.

Impact of Weight Change in Adults with Type 2 Diabetes Mellitus: A Literature Review and Critical Analysis.

OBJECTIVE: Weight reduction is a key component of diabetes management in adults with type 2 diabetes mellitus (T2DM), yet the benefits of weight loss in T2DM patients have been difficult to quantify. We examined the medical literature regarding the relationships between weight change and 1) glycemic control and 2) cost and resource use. METHODS: Systematic searches were conducted in the electronic databases Embase, MEDLINE, and the Cochrane Database of Systematic Reviews to identify publications regarding the impact of weight change on T2DM outcomes from 2007 onward. Identified publications were screened for relevance against predefined eligibility criteria, and methodological approaches and results were extracted. Evidence for the impact of weight change on outcomes was evaluated and used to identify strengths, limitations, and gaps in the current literature. RESULTS: The number of studies meeting eligibility criteria for each outcome was: glycemic control (n=38) and cost and resource use (n=11). The relationship between weight change and glycemic control was dependent on the interplay of multiple factors, eg, the weight loss interventions employed, the antidiabetic medication classes used, the time horizon, and baseline BMI and glycemic control. With respect to cost and resource use, the review indicated that savings were associated with weight loss, and increased costs were associated with weight gain. CONCLUSION: Studies regarding weight change in T2DM patients demonstrated varying effects on glycemic control and a positive association with costs and resource use, where weight loss was associated with decreased costs and resource use. Future studies may be able to clarify these relationships.

Hemophilia without prophylaxis: Assessment of joint range of motion and factor activity.

BACKGROUND: Recurrent joint bleeding in hemophilia results in arthropathy and functional impairment. The relationship of arthropathy development and factor activity (FA) has not been reported in patients with FA levels <15%-20%. METHODS: During the Centers for Disease Control and Prevention Universal Data Collection, joint range-of-motion (ROM) measurements were taken at each comprehensive visit. Data were extracted from male patients with hemophilia (PWH) age ≥2 years with baseline factor activity levels ≤40%, excluding those prescribed prophylaxis, and used to calculate a proportion of normal ROM (PN-ROM) measure. Data were analyzed using regression models. RESULTS: There were 6703 eligible PWH with 30 102 visits. PN-ROM declined with increasing age, and was associated with hemophilia severity, race/ethnicity, obesity, and viral illnesses. PWH ≥30 years old with fFA ≤2% and those ≥50 years old with FA ≤5% had mean PN-ROM values >10% less than controls; those ≥40 years old with FA <1% had values >20% less than controls. In the multivariable analysis, subjects with <1% FA had a 0.43% greater decrease (-0.49 to -0.37, 95% confidence interval) in PN-ROM each year relative to those with 16%-40% factor activity. A less pronounced effect was seen with 1%-5% or 6%-9% FA. CONCLUSION: The effect of FA on ROM loss is far greater than that of any of the other characteristics, especially with FA <10%. This emphasizes the need to maintain a high index of suspicion for arthropathy in individuals with moderate and low-mild hemophilia.

Healthcare Costs of Diabetes and Microvascular and Macrovascular Disease in Individuals with Incident Type 2 Diabetes Mellitus: A Ten-Year Longitudinal Study.

OBJECTIVE: The objective of this study was to estimate the incremental long-term costs associated with T2DM attributable to vascular diseases. RESEARCH DESIGN AND METHODS: This retrospective cohort study identified newly diagnosed (incident) T2DM patients in 2007 (baseline to 01/01/2006) using the HealthCore Integrated Research Database, a repository of nationally representative claims data. Incident T2DM patients were 1:1 exact matched on age, gender and other factors of interest to non-DM patients, and followed until the earlier of 8 follow-up years or death. Patients with documented vascular disease diagnosis were identified during the study period. All-cause and T2DM/vascular disease-related annual healthcare costs were examined for each follow-up year. RESULTS: The study included 13,883 individuals with T2DM and matched non-DM controls. Among individuals with T2DM, 11,792 (85%) had vascular disease versus 9251 (66.6%) non-T2DM between 01/01/2006 and 12/31/2015. Among T2DM patients, mean all-cause annual costs were greater than in non-T2DM patients ($13,806 vs $7,243, baseline, $21,745 vs $8,524, post-index year 1, $12,756-$14,793 vs $8,349-$9,940 years 2-8, p< 0.001), respectively. A similar trend was observed for T2DM/vascular disease-related costs (p< 0. 001). T2DM/vascular disease-related costs were largest during post-index year 1, accounting for the majority of all-cause cost difference between T2DM patients and matched non-DM controls. Incident T2DM individuals without vascular disease at any time had significantly lower costs compared to non-DM controls (p< 0. 001) between years 2-8 of follow-up. CONCLUSION: Vascular disease increased the cost burden for individuals with T2DM. The cost impact of diabetes and vascular disease was highest in the year after diagnosis, and persisted for at least seven additional years, while the cost of T2DM patients without vascular disease trended lower than for matched non-DM patients. These data highlight potential costs that could be offset by earlier and more effective detection and management of T2DM aimed at reducing vascular disease burden.

Correlations between patient-reported outcomes and self-reported characteristics in adults with hemophilia B and caregivers of children with hemophilia B: analysis of the B-HERO-S study.

PURPOSE: Pain, anxiety, depression, and other aspects of health-related quality of life (HRQoL) are important issues for people with hemophilia and caregivers of children with hemophilia. Patient-reported outcome (PRO) instruments may be used to assess aspects of HRQoL; however, the use of PROs in clinical management of patients with hemophilia is limited and inconsistent. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the impact of hemophilia B on HRQoL and other psychosocial aspects in affected adults and caregivers of children with hemophilia B. This post hoc analysis assessed correlations between PRO scores and psychosocial questions commonly asked in comprehensive care settings among B-HERO-S respondents. PATIENTS AND METHODS: B-HERO-S consisted of two online surveys, one administered to adults with hemophilia B (n=299) and one administered to caregivers of children with hemophilia B (n=150). The adult survey included EQ-5D-5L with visual analog scale, BPI, HAL, and PHQ-9. The caregiver survey included PHQ-9 and GAD-7. Questions related to demographics, hemophilia treatment, and psychosocial questions asked in comprehensive care visits were also included in the surveys. A post hoc analysis was performed to assess correlations between responses to selected psychosocial questions with PRO scores. RESULTS: For adults with hemophilia B, greater pain severity and pain interference scores were associated with work-related problems, functional limitations, and relationship, psychological, and treatment issues. Significant correlations were also noted between some of these psychosocial outcomes and depressive symptoms. For caregivers, greater depression and anxiety were associated with employment issues, their child's functional, relationship, and psychological issues, having had difficulty or concerns with treatment/factor availability or affordability, and having less frequent HTC visits. CONCLUSION: High correlations were observed between PRO scores measuring pain, depression, and anxiety and questions commonly used in the comprehensive care setting to assess the psychosocial impact of hemophilia.

Incidence and Prevalence of Microvascular and Macrovascular Diseases and All-cause Mortality in Type 2 Diabetes Mellitus: A 10-year Study in a US Commercially Insured and Medicare Advantage Population.

PURPOSE: The relationship between type 2 diabetes mellitus (T2DM) and increased microvascular and macrovascular disease and mortality is well established; however, data for the broad US T2DM population, especially by age, are limited. To help address this issue, we conducted a cohort study in a large national US commercially insured/Medicare Advantage population that incorporated a broad range of different age groups, including a large subset of younger individuals, during a 10-year study period. METHODS: This longitudinal study combined health plan claims and mortality data to identify incident T2DM patients and 1:1 directly matched non-DM controls. T2DM individuals (n = 13,883) were identified by a medical claim with a T2DM diagnosis or T2DM medication pharmacy claim in 2007; non-DM controls had no DM medical or pharmacy claims over the entire study period (January 1, 2006 to December 31, 2015). The outcomes assessed were incidence, prevalence, time to vascular disease and all-cause mortality, as well as age-stratified incidence and mortality based on Centers of Disease Control and Prevention-defined age strata. FINDINGS: Individuals with T2DM developed vascular disease at twice the rate as non-DM controls, 197 versus 98 per 1000 person-years, respectively. Vascular disease (composite) rates increased by age in T2DM/non-DM groups, 107.1/28.2 (18-44 years), 166.3/70.3 (45-64 years), and 391.0/199.7 (≥65 years) per 1000 person-years. The largest rate ratio was observed in younger individuals. All-cause mortality over follow-up was higher in T2DM individuals (27.5%) than in non-DM controls (19.6%). The largest increases in vascular disease prevalence and mortality among T2DM individuals were observed in the first year of follow-up. IMPLICATIONS: T2DM has a substantial effect on microvascular and macrovascular disease and all-cause mortality rates in all age groups. These outcomes appear to occur early after T2DM diagnosis, and have more pronounced, nearly fourfold, relative impact on younger individuals with T2DM compared to matched non-DM controls.

Injectable Antihyperglycemics: A Systematic Review and Critical Analysis of the Literature on Adherence, Persistence, and Health Outcomes.

INTRODUCTION: Improving real-world medication adherence to injectable antihyperglycemics in type 2 diabetes mellitus (T2DM) is a clinical challenge. Quantification of the level of adherence required to achieve a minimal clinically important difference (MCID) in glycemic control would assist in meeting this goal. The study objective was to review the literature regarding the relationships of medication adherence and persistence with health outcomes in adult T2DM patients using injectable antihyperglycemics. METHODS: Systematic searches were conducted using electronic databases to identify publications over the last decade. Publications were screened against established eligibility criteria. Study data were extracted, evaluated, and used to identify strengths, limitations, and gaps in current evidence. RESULTS: Eligibility criteria were met by 38 studies, and this report analyzed 34 studies related to glycemic control (n = 25), healthcare resource use (n = 9), and healthcare costs (n = 14). Eight of these studies examined adherence to glucagon-like peptide-1 receptor agonists (GLP-1 RA), including 1 study regarding adherence to GLP-1 RA or to insulin, and 1 study investigating a GLP-1 RA/insulin combination; the remaining studies involved insulin. Studies used a broad range of measures to classify adherence and persistence, and most measures were unable to reliably evaluate the complexities of patient behavior over time. Better adherence to injectable antihyperglycemic medications was generally found to be associated with improved glycemic control, although no studies attempted to identify a MCID. Although higher diabetes-related pharmacy and total healthcare costs were reported for adherent or persistent patients, these patients tended to have lower diabetes-related and all-cause medical costs. CONCLUSION: Results of this review confirmed the effectiveness of injectable antihyperglycemic medications for glycemic control, suggesting that there are clinical and financial consequences to nonadherence. Although attempts were made to quantify the effects of nonadherence, the interpretation of study results was limited by the lack of a MCID and inadequate study design. FUNDING: Novo Nordisk, Inc., Plainsboro Township, NJ, USA. Plain language summary available for this article.

Correction to: A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA.

The article "A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA", written by Pierre Johansen, Barnaby Hunt, Neeraj N. Iyer, Tam Dang-Tan, Richard F. Pollock was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 27, 2018 without Open Access.

A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release and Dulaglutide for Bringing Patients to HbA1c and Weight Loss Treatment Targets in the USA.

INTRODUCTION: The SUSTAIN 3 and 7 clinical trials compared the efficacy and safety of once-weekly semaglutide relative to exenatide extended-release (ER) and dulaglutide, respectively, in the treatment of patients with type 2 diabetes (T2D). The trials included a series of clinically relevant single and composite endpoints focused on improving glycemic control and reducing body weight, while avoiding hypoglycemia. The present study combined SUSTAIN 3 and 7 outcomes with short-term treatment costs to evaluate the relative cost of control of once-weekly semaglutide versus exenatide ER and dulaglutide. METHODS: Proportions of patients reaching three endpoints were taken from SUSTAIN 3 and 7 for comparisons with exenatide ER and dulaglutide, respectively. The endpoints investigated were HbA1c < 7.0%, HbA1c < 7.0% without hypoglycemia or weight gain, and a ≥ 1.0% HbA1c reduction with ≥ 5.0% weight loss. Annual per patient treatment costs were based on US wholesale acquisition costs from July 2018. Relative cost of control was calculated by plotting the ratio of the treatment costs and the ratio of the proportions of patients reaching each endpoint on the cost-efficacy plane. RESULTS: Once-weekly semaglutide 0.5 mg and 1.0 mg were most effective at bringing patients to each of the three endpoints across both SUSTAIN trials. The efficacy-to-cost ratios for once-weekly semaglutide 0.5 mg and 1.0 mg were also superior to all comparators when assessing both the single endpoint of HbA1c < 7.0% and the two composite endpoints including weight loss and hypoglycemia. CONCLUSIONS: The present study showed that once-weekly semaglutide 0.5 mg and 1.0 mg offer superior cost of control versus exenatide ER and dulaglutide in terms of achieving single and composite endpoints, based on an analysis of retrieved dropout data. Once-weekly semaglutide 0.5 mg and 1.0 mg would therefore represent good value for money in the USA, particularly in the attainment of multi-model T2D treatment goals. FUNDING: Novo Nordisk A/S.

Effect of Weight Change on Economic Outcomes Among Persons with Type 2 Diabetes Mellitus in the United States: Beyond Glycemic Control.

BACKGROUND: Previous studies report weight loss to be associated with significantly lower total health care costs among patients with type 2 diabetes mellitus (T2DM). The effect of weight change on health care costs, independent of glycemic control and after controlling for time-varying covariates among T2DM patients, remains unknown. OBJECTIVE: To evaluate the effect of weight change, independent of glycemic control, on all-cause and T2DM-related health care resource utilization (HCRU) and costs among T2DM patients in the United States. METHODS: A retrospective cohort study was conducted using a linked data extract composed of IQVIA's RWI Data Adjudicated Claims-US and Ambulatory Electronic Medical Record data. Adults (aged ≥ 18 years) with T2DM receiving ≥ 1 oral antidiabetic drug (OAD) medication, glucagon-like peptide-1 receptor agonist (GLP-1RA), and/or short- or long-acting insulin between January 1, 2010, and December 31, 2014 were included (the date of the first observed medical claim with a diagnosis code or medication prescription claim was the index date). Baseline characteristics were evaluated in the 6-month pre-index period. Weight loss (3%, 5%, or 7% from baseline) was evaluated over two 6-month periods (months 1-6 and 7-12) following the index date. Covariates included time-varying weight, hemoglobin A1c (A1c), costs, and HCRU within each 6-month period. Outcomes of interest (all-cause and T2DM-related HCRU and costs) were evaluated in the 6-month (months 13-18) and 12-month (months 13-24) periods following the initial 1- to 6-month and 7- to 12-month post-index periods. Structural nested mean models were used to evaluate the effect of weight change on these outcomes, independent of glycemic control. RESULTS: 1,407 patients were included (mean age = 55 years; 55% male), with a mean baseline weight of 102.2 kg (median = 99.7 kg) and a mean baseline A1c of 7.4% (median = 6.9%). In adjusted analysis, weight loss was associated with significantly lower all-cause and T2DM-related annual total health care costs. Compared with those showing no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $500, $800, and $1,100 in savings, respectively, in all-cause annual total health care costs per patient in the year following the weight loss. Similarly, compared with those with no weight change, a 3%, 5%, and 7% weight loss resulted in approximately $200, $300, and $400 in savings, respectively, in T2DM-related annual total health care costs per patient in the following year. Even greater savings (up to ~$2,000 and ~$800 in all-cause and T2DM-related annual costs per patient, respectively) were experienced by those who lost weight compared with those who gained weight. CONCLUSIONS: After accounting for glycemic control, this study found that weight loss was associated with additional significant reductions in all-cause and T2DM-related annual total health care costs. Understanding the role of weight loss in T2DM may provide useful evidence for decision makers as they evaluate therapy options for T2DM. DISCLOSURES: This study was funded by Novo Nordisk. Dang-Tan, Smolarz, and Iyer are employees of Novo Nordisk. Karkare and DeKoven (employees of IQVIA) and Fridman (employed by AMF Consulting) were contracted by Novo Nordisk to conduct this study. Fridman also reports personal fees from Shire, GSK, and CSL Behring, outside of the submitted work. Lu, an employee of IQVIA, accessed the database and conducted the statistical analysis for this study.

Cost-effectiveness and budget impact of liraglutide in type 2 diabetes patients with elevated cardiovascular risk: a US-managed care perspective.

BACKGROUND: The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcomes Results (LEADER) clinical trial demonstrated that liraglutide added to standard-of-care (SoC) therapy for type 2 diabetes (T2D) with established cardiovascular disease (CVD) or elevated cardiovascular (CV) risk was associated with lower rates of death from CVD, nonfatal myocardial infarction (MI), or nonfatal stroke than SoC alone. OBJECTIVE: The objective of this study was to assess the cost-effectiveness (CE) and budget impact of liraglutide vs SoC in T2D patients with established CVD or elevated CV risk, over a lifetime horizon from a US managed care perspective. METHODS: A cohort state-transition model (costs and benefits discounted at 3% per year) was used to predict diabetes-related complications and death (CV and all-cause). Events, treatment effects, and discontinuation rates were from LEADER trial; utility and cost data (US$, 2017) were from literature. Sensitivity analysis explored the impact of uncertainty on results. Additionally, a budget impact analysis was conducted to evaluate the financial impact of liraglutide use in this population, with displacement from dulaglutide, assuming a health care plan with 1 million members. RESULTS: Liraglutide patients experienced 6.3% fewer events, had event-related cost-savings of $15,182, gained additional life-years of 0.67 and quality-adjusted life-years (QALYs) of 0.57, and had additional total costs ($60,928) vs SoC. Liraglutide was cost-effective with an incremental CE ratio of $106,749/QALY which was below the willingness-to-pay threshold of $150,000/QALY accepted by the Institute of Clinical and Economic Research. Liraglutide was cost-effective across all sensitivity analyses, except when the hazard ratio for all-cause mortality varied. The budget impact was neutral, with a per-plan-per-year and per-member-per-month cost-savings of $266,334 and $0.02, respectively. CONCLUSION: From a US-managed care perspective, for T2D patients with established CVD or elevated CV risk, liraglutide is a cost-effective and a budget neutral treatment option for health care plans.

Incremental health care resource utilization and expenditures associated with autosomal-dominant polycystic kidney disease.

PURPOSE: Incremental health care resource utilization and expenditures associated with autosomal dominant polycystic kidney disease (ADPKD) were estimated. METHODS: Study data were from a large administrative claims database. Individuals aged 18 years or older enrolled in tracked health plans for 12 months from April 1, 2011 through March 31, 2012, and with an International Classification of Disease, Ninth Revision, Clinical Modification diagnosis code for "polycystic kidney, autosomal dominant" (753.13) or for "polycystic kidney, unspecified type" (753.12) were identified as having ADPKD, and linked one-to-one with individuals without ADPKD based on age and gender. Zero-inflated negative binomial models estimated incremental health care resource utilization and expenditures, adjusting for risk factors. RESULTS: A total of 3,844 individuals with ADPKD who satisfied selection criteria were linked one-to-one with 3,844 individuals without ADPKD. Multivariate, regression models adjusting for risk factors revealed incremental mean (standard error) resource use associated with ADPKD of 0.68 (0.090) hospital days, equal to 68 additional hospital days per 100 ADPKD patients, and 6.9 (0.28) outpatient visits, equal to 690 additional visits per 100 ADPKD patients. Mean (standard error) incremental total expenditures associated with ADPKD were US$8,639 ($470). Mean incremental expenditures were largest for outpatient expenditures at US$4,918 ($198), followed by mean incremental hospital expenditures of US$2,603 ($263), and mean incremental medication expenditures of US$1,589 ($77). Based on sub-group analysis, mean incremental total expenditures were US$2,944 ($417) among ADPKD patients without end-stage renal disease and US$38,962 ($6,181) for those with end-stage renal disease. CONCLUSION: ADPKD was associated with considerable incremental health care resource utilization and expenditures. Significant illness burden was found even before patients reached end-stage renal disease.

Reliability and validity of patient-reported outcome instruments in US adults with hemophilia B and caregivers in the B-HERO-S study.

OBJECTIVE: To assess the reliability and validity of six patient-reported outcomes (PRO) instruments for evaluating health-related quality of life in adults with mild-severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls. METHODS: Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ-5D-5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ-9]), or caregivers only (Generalized Anxiety Disorder 7-Item [GAD-7] scale). Construct validity and item-total correlation were assessed using Pearson product-moment correlation, internal consistency was assessed using Cronbach's alpha coefficient, and known-group validity was assessed by comparisons to self-reported characteristics based on the Kruskal-Wallis test. RESULTS: Patient-reported outcomes instruments generally showed satisfactory reliability for adults (n = 299) and caregivers (n = 150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ-9 and GAD-7 did not show significant differences among caregiver age groups. CONCLUSIONS: Patient-reported outcomes instruments administered in B-HERO-S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders.

Cost of Achieving HbA1c Treatment Targets and Weight Loss Responses with Once-Weekly Semaglutide Versus Dulaglutide in the United States.

INTRODUCTION: The National Health and Nutrition Examination Surveys show that many people with type 2 diabetes (T2D) in the USA fail to achieve recommended treatment targets. In the SUSTAIN 7 randomized controlled trial, once-weekly semaglutide (0.5 and 1.0 mg) was superior to comparative doses of dulaglutide (0.75 and 1.5 mg) in reducing glycated hemoglobin (HbA1c) and body weight in people with T2D. The present study estimated the cost per patient achieving HbA1c treatment targets and weight loss responses with once-weekly semaglutide and dulaglutide in the USA. METHODS: Numbers needed to treat and annual cost per patient achieving HbA1c targets (including a triple composite endpoint of HbA1c < 7% without hypoglycemia and no weight gain) or weight loss responses were calculated on the basis of data from SUSTAIN 7 and the annual cost of treatment from a US healthcare payer perspective. RESULTS: More patients reached HbA1c targets with once-weekly semaglutide than with dulaglutide, and once-weekly semaglutide showed lower costs of control for all modeled endpoints. The cost per patient achieving the triple composite endpoint was USD 11,916 with once-weekly semaglutide 1.0 mg and USD 15,204 with dulaglutide 1.5 mg, representing a 28% larger cost with dulaglutide 1.5 mg. The cost of reaching the target was 68% larger with dulaglutide 0.75 mg versus once-weekly semaglutide 0.5 mg. For each patient achieving an HbA1c < 7%, the cost would be 18% larger with dulaglutide 1.5 mg than with once-weekly semaglutide 1.0 mg. CONCLUSIONS: The cost of bringing one patient to the triple composite endpoint of an HbA1c < 7% without hypoglycemia and no weight gain would be 28% and 68% higher with dulaglutide 1.5 mg relative to once-weekly semaglutide 1.0 mg and dulaglutide 0.75 mg relative to once-weekly semaglutide 0.5 mg, respectively. Once-weekly semaglutide therefore provides better value for money than dulaglutide for the treatment of people with T2D in the USA. FUNDING: Novo Nordisk A/S.

Factors associated with pain severity, pain interference, and perception of functional abilities independent of joint status in US adults with hemophilia: Multivariable analysis of the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

INTRODUCTION: Levels of pain and dysfunction appear to differ among people with hemophilia despite similar levels of joint disease. OBJECTIVE: To determine patient characteristics that influence pain and function independent of joint status. METHODS: US adults with hemophilia completed a survey that included information on clinical characteristics, demographics, and patient-reported outcome instruments assessing pain (Brief Pain Inventory v2 Short Form [BPI]), functional impairment (Hemophilia Activities List [HAL]), and health status (EQ-5D-5L). Additionally, physiotherapists optionally completed a clinical joint evaluation (Hemophilia Joint Health Score [HJHS]). Associations were examined using simple and multiple regression models. RESULTS: Of 381 adults enrolled, 240 had complete HJHS scores (median age, 32 years). After controlling for HJHS and opiate use, anxiety/anxiolytic use was significantly associated with worse pain severity and interference scores. After controlling for HJHS, the most significant predictors of functional impairment were older age, unemployment, more severe hemophilia, and greater pain. EQ-5D-5L pain/discomfort was associated with worse outcomes on most HAL scores. CONCLUSION: Unemployment, anxiety, and depression were each associated with both greater pain and functional disability after controlling for joint status. Continued attention to pain and psychosocial issues will be important in improving clinical care and research efforts in the hemophilia population.

Patient-reported outcomes and joint status across subgroups of US adults with hemophilia with varying characteristics: Results from the Pain, Functional Impairment, and Quality of Life (P-FiQ) study.

INTRODUCTION: Pain and functional impairment associated with joint disease are major problems for people with hemophilia, and impact on health-related quality of life (HRQoL) may vary across groups defined by demographic and treatment-related characteristics. OBJECTIVE: To evaluate differences in overall HRQoL, pain, function, and joint status between P-FiQ study subgroups. METHODS: Adult males with hemophilia and a history of joint pain/bleeding completed a pain history and the patient-reported outcome instruments EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), International Physical Activity Questionnaire (IPAQ), and Hemophilia Activities List (HAL); optionally, joint status was assessed (Hemophilia Joint Health Score v2.1 [HJHS]). Scores were analyzed between subgroups across sets of participant characteristics. RESULTS: A total of 381 adult males with hemophilia were enrolled, with median age of 34 years. Worse scores on EQ-5D-5L index, BPI pain severity/interference, HAL overall score, and HJHS were generally associated with being college educated, unemployment, self-reporting both acute and chronic pain, and self-reporting anxiety/depression. CONCLUSIONS: Measures of joint status and HRQoL were consistently lower in participants who had higher educational levels, were unemployed, self-reported having both acute and chronic pain, and self-reported having anxiety/depression. A greater understanding of the association of these factors with disease outcomes may improve individualized patient management.

Impact of hemophilia B on quality of life in affected men, women, and caregivers-Assessment of patient-reported outcomes in the B-HERO-S study.

INTRODUCTION: Health-related quality of life (HRQoL) is impaired in patients with hemophilia; however, the impact in mild/moderate hemophilia B and affected women is not well characterized. OBJECTIVE: To evaluate factors that affect HRQoL in adults with hemophilia B and caregivers of affected children. METHODS: US adult patients and caregivers of affected children completed distinct ~1-hour online surveys including patient-reported outcome instruments. RESULTS: In total, 299 adult patients and 150 caregivers participated. Adults with moderate hemophilia reported poorer health status (median EQ-5D-5L index score, 0.63) than those with mild (0.73) or severe (0.74) hemophilia. Women reported greater pain severity than men on the Brief Pain Inventory v2 Short Form (median, 7.00 vs 5.00). Based on the Patient Health Questionnaire, mild or worse depression was observed in >50% of adult respondents, and depression was reported more often in those with moderate and severe hemophilia vs those with mild hemophilia. Most caregivers reported at least mild depression. CONCLUSION: Pain, functional impairment, and depression/anxiety are present at higher-than-expected levels in individuals with hemophilia B. The large proportion of individuals with mild/moderate hemophilia and women with reduced health status suggests significant unmet needs in this population.

Internal consistency and item-total correlation of patient-reported outcome instruments and hemophilia joint health score v2.1 in US adult people with hemophilia: results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

BACKGROUND: The Pain, Functional Impairment, and Quality of Life study was an observational, cross-sectional assessment of the impact of pain on functional impairment and quality of life in adult people with hemophilia (PWH) of any severity in the USA who experience joint pain and/or bleeding. OBJECTIVE: To assess internal consistency (IC) and item-total correlation (ITC) of assessment tools used in the Pain, Functional Impairment, and Quality of Life study. METHODS: Participants completed 5 patient-reported outcome instruments (EQ-5D-5L with visual analog scale, Brief Pain Inventory v2 Short Form [BPI], International Physical Activity Questionnaire [IPAQ], Short Form 36 Health Survey v2 [SF-36v2], and Hemophilia Activities List [HAL]) and underwent an optional physiotherapist-administered musculoskeletal exam (Hemophilia Joint Health Score v2.1) during routine visits. Reliability assessment included IC and ITC of each instrument. RESULTS: A total of 381 adult PWH (median age, 34 years) were enrolled. Participants were predominantly white/non-Hispanic (69.2%); 75% had congenital hemophilia A, and 70.5% had severe hemophilia. A total of 310 subjects reported bleeding within the past 6 months (mean [SD] number of bleeds, 7.1 [13.00]). IC was generally high across the instruments employed (Cronbach's alpha 0.79-0.98) with the exception of HAL use of transportation (0.58) and IPAQ total physical activity (0.51). ITC was high (Pearson's product-moment correlation coefficient >0.20) for all items except the "vigorous intensity activities" item of IPAQ, which was applicable to less than one-third of participants. The ITCs were generally highest in domains/scores that measured the functional consequences of hemophilic arthropathy on mobility and pain. CONCLUSION: The demonstrated reliability (IC/ITC) of the patient-reported outcome instruments and Hemophilia Joint Health Score v2.1 support a role for these instruments in evaluating adult PWH in US clinical and research settings.