Healthcare resource utilisation and direct medical cost for individuals with 5q spinal muscular atrophy in Sweden.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, progressive, neuromuscular disorder. Recent advances in treatment require an updated assessment of burden to inform reimbursement decisions. OBJECTIVES: To quantify healthcare resource utilisation (HCRU) and cost of care for patients with SMA. METHODS: Cohort study of patients with SMA identified in the Swedish National Patient Registry (2007-2018), matched to a reference cohort grouped into four SMA types (1, 2, 3, unspecified adult onset [UAO]). HCRU included inpatient admissions, outpatient visits, procedures, and dispensed medications. Direct medical costs were estimated by multiplying HCRU by respective unit costs. Average annual HCRU and medical costs were modelled for SMA versus reference cohorts to estimate differences attributable to the disease (i.e., average treatment effect estimand). The trajectory of direct costs over time were assessed using synthetic cohorts. RESULTS: We identified 290 SMA patients. Annualised HCRU was higher in SMA patients compared with reference cohorts. Highest risk ratios were observed for inpatient overnight stays for type 1 (risk ratio [RR]: 29.2; 95% confidence interval [CI]: 16.0, 53.5) and type 2 (RR: 23.3; 95% CI: 16.4,33.1). Mean annual direct medical costs per patient for each year since first diagnosis were greatest for type 1 (€114,185 and SMA-attributable: €113,380), type 2 (€61,876 and SMA-attributable: €61,237), type 3 (€45,518 and SMA-attributable: €44,556), and UAO (€4046 and SMA-attributable: €2098). Costs were greatest in the 2-3 years after the first diagnosis for all types. DISCUSSION AND CONCLUSION: The economic burden attributable to SMA is significant. Further research is needed to understand the burden in other European countries and the impact of new treatments.

Corrigendum: Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

[This corrects the article DOI: 10.3389/ti.2022.10528.][This corrects the article DOI: 10.3389/ti.2023.12367.].

Estimating Changes in Weight and Metabolic Parameters Before and After Treatment With Cariprazine: A Retrospective Study of Electronic Health Records.

PURPOSE: Weight gain and associated negative cardiometabolic effects can occur as a result of mental illness or treatment with second-generation antipsychotics (SGAs), leading to increased rates of morbidity and mortality. In this analysis, we evaluated the effect of the SGA cariprazine on weight and metabolic parameters in a real-world, retrospective, observational dataset. METHODS: Electronic health records from the Optum Humedica database (October 1, 2014-December 31, 2020) were analyzed during the 12-month period before starting cariprazine (baseline) and for up to 12 months following cariprazine initiation; approved and off-label indications were included. Body weight trajectories were estimated in the overall patient cohort and at 3-, 6-, and 12-month timepoints (primary objective). Changes in hemoglobin A1c (HbA1c), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were also evaluated (secondary objectives). Percentages of patients with clinically relevant shifts in body weight, total cholesterol, and fasting triglycerides were also determined. Discontinuation rates for metabolic regulating medications were calculated. Average predicted values were estimated by linear mixed-effects regression models. FINDINGS: A total of 2,301 patients were included; average duration of follow-up was 133.7 days. Average predicted weight change for patients during the cariprazine overall follow-up period was +2.4 kg, with predicted weight changes of +0.8 kg (n = 811), +1.1 kg (n = 350), and +1.4 kg (n = 107) at months 3, 6, and 12, respectively. Overall, the majority of patients did not experience clinically significant (≥7%) weight gain (82.8%) or loss (90.5%) after starting cariprazine. Average predicted HbA1c levels (n = 189) increased during baseline (0.15%/year) and decreased during cariprazine treatment (-0.2%/year). Average predicted triglyceride levels (n = 257) increased during baseline (15.0 mg/dL/year) and decreased during cariprazine treatment (-0.7 mg/dL/year). Predicted LDL (n = 247) and HDL (n = 255) values decreased during baseline (-7.3 and -1.1 mg/dL/year, respectively); during cariprazine treatment, LDL increased by 5.6 mg/dL/year and HDL decreased by -0.6 mg/dL/year. During follow-up, most patients did not shift from normal/borderline to high total cholesterol (<240 to ≥240 mg/dL; 522 [90.2%]) or fasting triglyceride (<200 to ≥200 mg/dL; 143 [88.8%] patients) levels; shifts from high to normal/borderline levels occurred in 44 (61.1%) patients for total cholesterol and 38 (57.6%) patients for fasting triglycerides. After starting cariprazine, the discontinuation rate per 100 patient-years was 60.4 for antihyperglycemic medication and 87.4 for hyperlipidemia medication. IMPLICATIONS: These real-world results support short-term clinical trial findings describing a neutral weight and metabolic profile associated with cariprazine treatment and they expand the dataset to include long-term follow-up.

Use of electronic health data to identify patients with moderate-to-severe osteoarthritis of the hip and/or knee and inadequate response to pain medications.

BACKGROUND: No algorithms exist to identify important osteoarthritis (OA) patient subgroups (i.e., moderate-to-severe disease, inadequate response to pain treatments) in electronic healthcare data, possibly due to the complexity in defining these characteristics as well as the lack of relevant measures in these data sources. We developed and validated algorithms intended for use with claims and/or electronic medical records (EMR) to identify these patient subgroups. METHODS: We obtained claims, EMR, and chart data from two integrated delivery networks. Chart data were used to identify the presence or absence of the three relevant OA-related characteristics (OA of the hip and/or knee, moderate-to-severe disease, inadequate/intolerable response to at least two pain-related medications); the resulting classification served as the benchmark for algorithm validation. We developed two sets of case-identification algorithms: one based on a literature review and clinical input (predefined algorithms), and another using machine learning (ML) methods (logistic regression, classification and regression tree, random forest). Patient classifications based on these algorithms were compared and validated against the chart data. RESULTS: We sampled and analyzed 571 adult patients, of whom 519 had OA of hip and/or knee, 489 had moderate-to-severe OA, and 431 had inadequate response to at least two pain medications. Individual predefined algorithms had high positive predictive values (all PPVs ≥ 0.83) for identifying each of these OA characteristics, but low negative predictive values (all NPVs between 0.16-0.54) and sometimes low sensitivity; their sensitivity and specificity for identifying patients with all three characteristics was 0.95 and 0.26, respectively (NPV 0.65, PPV 0.78, accuracy 0.77). ML-derived algorithms performed better in identifying this patient subgroup (range: sensitivity 0.77-0.86, specificity 0.66-0.75, PPV 0.88-0.92, NPV 0.47-0.62, accuracy 0.75-0.83). CONCLUSIONS: Predefined algorithms adequately identified OA characteristics of interest, but more sophisticated ML-based methods better differentiated between levels of disease severity and identified patients with inadequate response to analgesics. The ML methods performed well, yielding high PPV, NPV, sensitivity, specificity, and accuracy using either claims or EMR data. Use of these algorithms may expand the ability of real-world data to address questions of interest in this underserved patient population.

Healthcare Service Use Patterns Among Patients with Acid Sphingomyelinase Deficiency Type B: A Retrospective US Claims Analysis.

INTRODUCTION: Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease. Patients with ASMD type B experience multiple morbidities, potentially leading to early mortality. Before the 2022 approval of olipudase alfa for non-neuronopathic ASMD manifestations, only symptom management was offered. Data on healthcare services used by patients with ASMD type B are limited. This analysis used medical claims data to evaluate real-world healthcare service use by patients with ASMD type B in the United States of America (USA). METHODS: The IQVIA Open Claims patient-level database (2010-2019) was cross-examined. Two patient cohorts were identified: the primary analysis cohort, which included patients with at least two claims associated with ASMD type B (ICD-10 code E75.241) and more total claims with ASMD type B than any other ASMD types, and the sensitivity analysis cohort, which included patients with a high probability of having ASMD type B identified using a validated machine-learning algorithm. Claims for ASMD-associated healthcare services were recorded, including outpatient visits, emergency department (ED) visits, and inpatient hospitalizations. RESULTS: The primary analysis cohort included 47 patients; a further 59 patients made up the sensitivity analysis cohort. Patient characteristics and healthcare service use were similar in both cohorts and were consistent with established characteristics of ASMD type B. Overall, 70% of the primary analysis cohort from this study were aged < 18 years, and the liver, spleen, and lungs were the most frequently affected organs. Cognitive, developmental, and/or emotional problems and respiratory/lung disorders caused most outpatient visits; respiratory/lung disorders accounted for most ED visits and hospitalizations. CONCLUSION: This retrospective analysis of medical claims data identified patients with ASMD type B who had characteristics typical of this condition. A machine-learning algorithm detected further cases with a high probability of having ASMD type B. High use of ASMD-related healthcare services and medications was observed in both cohorts.

Acid sphingomyelinase deficiency (ASMD) type B, historically known as Niemann­Pick type B, is a rare illness. People with acid sphingomyelinase deficiency type B experience damage to many organs of the body (such as the liver and lungs), which may lead to early death. Until recently, no treatment has been available, and people were only treated for their symptoms. Now, a treatment called olipudase alfa has been approved in Europe, Japan, and the USA. People with ASMD type B may need lots of tests, surgeries, medications, and physician visits; however, we do not know how often these healthcare services are used. This study used medical claims to find out more about the healthcare services used by people with ASMD type B. To find as many people with ASMD type B as possible, we identified two groups of people. The first group included people with diagnosis codes for ASMD type B, the other group was identified as having a high likelihood of ASMD type B. The people in each group were similar in age and the illnesses/symptoms they had. The liver, spleen, and lungs were the most frequently damaged organs, and most physician visits were for mental, developmental, and/or emotional problems, and breathing or lung diseases. Breathing or lung disease and bleeding problems caused the most emergency department visits and hospitalizations. Overall, the use of healthcare services was high in people with ASMD type B. This study shows the need for specific treatments for people with ASMD.

Real-World Treatment Patterns of Antiviral Prophylaxis for Cytomegalovirus Among Adult Kidney Transplant Recipients: A Linked USRDS-Medicare Database Study.

Limited data exist on cytomegalovirus (CMV) antiviral treatment patterns among kidney transplant recipients (KTRs). Using United States Renal Database System registry data and Medicare claims (1 January 2011-31 December 2017), we examined CMV antiviral use in 22,878 KTRs who received their first KT from 2011 to 2016. Three-quarters of KTRs started CMV prophylaxis (85.8% of high-, 82.4% of intermediate-, and 32.1% of low-risk KTRs). Median time to prophylaxis discontinuation was 98, 65, and 61 days for high-, intermediate-, and low-risk KTRs, respectively. Factors associated with receiving CMV prophylaxis were high-risk status, diabetes, receipt of a well-functioning kidney graft, greater time on dialysis before KT, panel reactive antibodies ≥80%, and use of antithymocyte globulin, alemtuzumab, and tacrolimus. KTRs were more likely to discontinue CMV prophylaxis if they developed leukopenia/neutropenia, had cardiovascular disease, or received their kidney from a deceased donor. These findings suggest that adherence to the recommended duration of CMV-prophylaxis for high and intermediate-risk patients is suboptimal, and CMV prophylaxis is overused in low-risk patients.

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.

Cost-effectiveness of valbenazine compared with deutetrabenazine for the treatment of tardive dyskinesia.

AIMS: To evaluate clinical and economic outcomes associated with valbenazine compared with deutetrabenazine in patients with tardive dyskinesia (TD) using a model that accounts for multiple dimensions of patient health status. MATERIALS AND METHODS: A discretely integrated condition event model was developed to evaluate the cost-effectiveness of treatment with valbenazine and deutetrabenazine in a synthetic cohort of 1,000 patients with TD who were receiving antipsychotic medication to treat an underlying psychiatric disorder. Clinical inputs were derived from relevant clinical trials or from publicly available sources. Patients were assessed over 1 year using ≥50% improvement from baseline in Abnormal Involuntary Movement Scale (AIMS) total score as the primary definition of response. Response at 1 year using Clinical Global Impression of Change (CGIC) score ≤2 was also assessed. Health outcomes included quality-adjusted life years (QALYs), life years, proportion responding to treatment at 1 year, and number of psychiatric relapses. RESULTS: Regardless of the definition used for response, patients treated with valbenazine were more likely to have responded to treatment at 1 year, lived longer, and accrued more QALYs than patients who received deutetrabenazine. Using the AIMS response criterion, the incremental cost-effectiveness ratio was $9,951/QALY for valbenazine compared with deutetrabenazine. By comparison, using the CGIC response criterion valbenazine dominated deutetrabenazine with valbenazine-treated patients accumulating more QALYs (3.4 vs 3.3 years) and incurring lower lifetime costs ($252,311 vs $283,208) than deutetrabenazine-treated patients. LIMITATIONS: There are no head-to-head trials of valbenazine and deutetrabenazine, so probabilities of response used in the model were calculated based on an indirect treatment comparison of results from individual trials with one drug or the other, using only those metrics reported across trials. CONCLUSIONS: In patients with TD, treatment with valbenazine is highly cost-effective compared with deutetrabenazine.

Oral Corticosteroid Treatment Patterns of Patients in the United States with Persistent Asthma.

BACKGROUND: Patients with poor asthma control may receive oral corticosteroid (OCS) therapy despite the risk for adverse effects. OBJECTIVE: We assessed OCS use frequency and treatment patterns in patients with persistent asthma in the United States (US). METHODS: We used the IBM MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid Multistate Claims research databases to identify patients from January 1, 2012, to December 31, 2017, who were ≥12 years old, met the 2-year Healthcare Effectiveness Data and Information Set criteria for persistent asthma, and were continuously enrolled ≥6 months before (baseline) and ≥24 months after (follow-up) the persistent asthma index date. Patients were classified as high OCS use (defined as ≥450 mg of OCS prescribed within a 90-day period during follow-up), low use (use OCS but not meeting high use criteria), or no OCS use. RESULTS: We identified 435,675 patients, of whom 65% used OCS and 19% were classified as high OCS users at some point during follow-up. The annual prevalence of high OCS use ranged from 5.3% in 2013 to 7.6% in 2017. During the entire follow-up, high and low OCS users filled an average of 2.2 and 0.8 OCS prescriptions and received an average daily dosage of 2.2 and 0.3 mg, respectively. Once the patients became high OCS users, the average daily OCS dosage was relatively stable (5.1-7.1 mg) over 3 years. CONCLUSIONS: Patients with persistent asthma in the US have substantial exposure to OCS. OCS therapy should be considered carefully to avoid associated adverse effects.

Healthcare resource utilization and cost among patients with type 1 diabetes in the United States.

BACKGROUND: Approximately 5%-10% of patients with diabetes are diagnosed with type 1 diabetes mellitus (T1DM), the incidence and prevalence of which is projected to increase through 2050. Despite this, T1DM-related health care resource utilization (HCRU) and economic burden in the United States have not been adequately assessed, since previous studies used various cost definitions and underlying methods to examine these outcomes. OBJECTIVE: To assess HCRU and costs incurred by patients with T1DM in the United States. METHODS: This retrospective cohort study used IBM Watson MarketScan data from 2011 to 2015 and Optum's electronic medical record (EMR) and integrated data (i.e., linked EMR and administrative claims data) from 2011 to 2016. Included patients had ≥ 1 T1DM diagnosis (the earliest diagnosis date was designated as the index date), were continuously enrolled for ≥ 6 months during their pre-index baseline periods, and had ≥ 1 pharmacy claim for insulin or an insulin pump within ± 90 days of the index date. Baseline demographic and clinical characteristics were summarized descriptively. Average monthly HCRU and costs per patient per month (PPPM) paid by the health plan and patient were assessed. Costs were adjusted for inflation to 2018 U.S. dollars. RESULTS: We identified 181,423 patients with T1DM who met the selection criteria in MarketScan, 84,759 in the Optum EMR, and 8,948 in the Optum integrated databases. Most patients were male (range across databases: 52.6%-53.1%), relatively young (medians: 33-35 years, overall range: 0-100 years), and had a Charlson Comorbidity Index score of 1 (69.2%-73.0%) across all databases. Total all-cause and diabetes-related costs ranged from $1,482 to $1,522 and $733 to $780 PPPM, respectively, during the follow-up period. Pharmacy costs contributed most to the total cost of care, accounting for 55.3% ($431) to 61.1% ($448) of total diabetes-related costs. On an annualized basis, patients had an average of 0.2-0.9 all-cause hospitalizations and 0.1-0.3 diabetes-related hospitalizations during follow-up. The median costs per diabetes-related hospitalization ranged from $6,548 to $8,439, accounting for 4%-7% of total monthly diabetes-related costs. Patients had an average of 0.4-0.5 all-cause and 0.1-0.2 diabetes-related emergency department (ED) visits annually; the median costs of ED visits were $972-$1,499, contributing about 2% of monthly diabetes-related costs during follow-up. CONCLUSIONS: In this large, retrospective, observational study of pediatric and adult patients with T1DM, diabetes-related costs totaled nearly $800 per month. Pharmacy costs contributed to over half of diabetes-related costs, indicating the substantial economic burden associated with the treatment of T1DM. Additional research is needed to determine risk factors associated with costly events (e.g., hospitalizations and ED visits) and indirect costs associated with T1DM. DISCLOSURES: JDRF International provided funding for this project and manuscript. JDRF International also contracted with Evidera, a research and consulting firm for the biopharma industry, for its participation in the project and in the development of this manuscript. The Leona M. and Harry B. Helmsley Charitable Trust provided JDRF International with funding. Simeone, Shah, and Ganz are employed by Evidera and do not receive any payment or honoraria directly from Evidera's clients. LeGrand is an employee of JDRF International. Bushman was employed by JDRF International during the conduct of the study and development of this manuscript. Sullivan and Koralova are employees of The Leona M. and Harry B. Helmsley Charitable Trust.

Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With Medication Use and Health Outcomes in Elderly Patients With Dementia.

Importance: Atypical antipsychotics (AAPs) are often used off-label to manage dementia-associated neuropsychiatric symptoms. In 2005, the US Food and Drug Administration (FDA) issued a boxed warning for the use of AAPs in elderly patients. The long-term association of this warning with health outcomes is unknown to date. Objective: To assess the long-term association of the 2005 FDA boxed warning on AAPs with psychiatric medication and opioid use, health events, and quality of life among elderly individuals with dementia. Design, Setting, and Participants: For this cross-sectional study, data were analyzed from the household component of the Medical Expenditure Panel Survey (MEPS), the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) fielded between January 1, 1996, and December 31, 2014. This interrupted time-series analysis applied to 3-year moving means derived from the 1996-2014 MEPS, NAMCS, and NHAMCS. All survey respondents included in this analysis were 65 years or older and had dementia. Data analysis was performed from December 1, 2017, to March 15, 2018. Exposures: The 2005 FDA boxed warning on AAPs. Main Outcomes and Measures: Use of psychiatric medications and opioids, prevalence of cerebrovascular and cardiovascular events, prevalence of falls and/or fractures, 2-year mortality, and health-related quality of life assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey scores. Results: A total of 2430 (MEPS) and 5490 (NAMCS and NHAMCS) respondents were identified, corresponding to weighted populations of 22 996 526 (MEPS) and 65 502 344 (NAMCS and NHAMCS) noninstitutionalized elderly individuals with dementia (mean [SD] age, 81.06 [1.13] years; 63.1% female). In the MEPS sample, compared with before 2005, AAP use (from an annual slope of 0.99 to -0.18 percentage points), cerebrovascular events (0.75 to -0.50 percentage points), and falls and/or fractures (-1.72 to -0.40 percentage points) decreased and opioid use (0.04 to 1.29 percentage points), antiepileptic use (-0.42 to 1.21 percentage points), cardiovascular events (-0.13 to 1.30 percentage points), and 2-year mortality risk (-0.68 to 0.18 percentage points) increased. Health-related quality of life remained relatively unchanged. The NAMCS and NHAMCS sample yielded similar findings. Conclusions and Relevance: These data suggest that the 2005 FDA boxed warning was associated with some unintended negative patient outcomes.

Public Health Impact and Cost-Effectiveness of Non-live Adjuvanted Recombinant Zoster Vaccine in Canadian Adults.

OBJECTIVES: In Canada, incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are increasing, posing a significant burden on the healthcare system. This study aimed to determine the public health impact and cost effectiveness of an adjuvanted recombinant zoster vaccine (RZV) compared to no vaccination and to the live attenuated vaccine (ZVL) in Canadians aged 60 years and older. METHODS: A multi-cohort Markov model has been adapted to the Canadian context using recent demographic and epidemiologic data. Simulations consisted of age-cohorts annually transitioning between health states. Health outcomes and costs were discounted at 1.5% per year. The perspective of the Canadian healthcare payer was adopted. A coverage of 80% for the first RZV and ZVL dose and a compliance of 75% for the second RZV dose were assumed. RESULTS: RZV was estimated to be cost effective compared with no vaccination with an incremental cost-effectiveness ratio (ICER) of $28,360 (Canadian dollars) per quality-adjusted life-year (QALY) in persons aged ≥ 60 years, avoiding 554,504 HZ and 166,196 PHN cases. Compared with ZVL, RZV accrued more QALYs through the remaining lifetime and an increase in costs of approximately $50 million resulting in an average ICER of $2396. Results were robust under deterministic and probabilistic sensitivity analyses. HZ incidence rate and persistence of vaccine efficacy had the largest impact on cost effectiveness. CONCLUSIONS: The cost-utility analysis suggested that RZV would be cost effective in the Canadian population compared with no vaccination and vaccination with ZVL at a willingness-to-pay threshold of $50,000.

More than 95% of adults aged 50 are infected with varicella-zoster virus and are at risk of developing herpes zoster, also known as shingles. This risk is higher in older people and in people with a reduced immune system. Shingles causes a painful rash and may trigger persistent pain and other complications that greatly reduce quality of life. In Canada, Zostavax is the only existing approved vaccine against shingles. It has been offered in a publicly funded program in Ontario to those aged 65­70 years since September 2016. Shingrix, is a new shingles vaccine that has recently been approved by Health Canada for adults aged ≥ 50 years. The present model suggests that Shingrix confers higher protection against shingles compared to Zostavax, with a greater reduction in shingles episodes. The increase in vaccination costs would be partially offset by reduced healthcare visit and medication expenses. For these reasons, provincial health plans may consider offering Shingrix to people aged ≥ 50 years.

Retrospective Cohort Analysis of the Reduced Burden of Hypoglycemia Associated with Dipeptidyl Peptidase-4 Inhibitor Use in Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The use of antihyperglycemic agents (AHA), especially insulin and sulfonylureas (SU), is a risk factor for hypoglycemia. Despite the significant clinical and economic burdens associated with hypoglycemia and the decreasing use of SU in favor of other oral AHA, relatively little is known about hypoglycemia trends specific to the use of non-insulin AHA. We sought to estimate annual hypoglycemia event rates and costs among patients with type 2 diabetes mellitus (T2DM) who started either SU or dipeptidyl peptidase-4 inhibitors (DPP-4i) and to predict rates and costs in the absence of DPP-4i. METHODS: Truven's MarketScan Commercial Claims database was used to estimate hypoglycemia event rates and costs from 2007 to 2013. Hypoglycemia, defined using diagnosis codes, was assessed during the 12 months following SU (n = 245,201) or DPP-4i (n = 176,786) initiation by adults with T2DM. Coefficients from a Poisson regression model used to estimate the impact of patient characteristics on hypoglycemia rates for patients who started SU were used to predict rates for patients who started DPP-4i had they started SU instead. RESULTS: Hypoglycemia events per 100 patient-years (costs per event) ranged from 5.4 ($565) in 2007 to 10.4 ($1154) in 2013 for patients starting SU; rates (costs) for patients starting DPP-4i ranged from 3.2 ($308) in 2007 to 6.4 ($482) in 2013. Predicted hypoglycemia rates would have been 5.3-9.9 per 100 person-years for patients who started DPP-4i had they started SU instead. Starting DPP-4i, rather than SU, would have resulted in national savings of $750.3 million in healthcare costs due to avoided hypoglycemia events during this period. CONCLUSIONS: Hypoglycemia rates and costs were consistently higher for patients who started SU rather than DPP-4i. The overall burden of hypoglycemia could be lowered substantially in the USA if, when feasible, patients with T2DM initiate DPP-4i instead of SU. FUNDING: Merck & Co., Inc., Kenilworth, NJ USA.

Economic burden of hospital admissions for patients with acute bacterial skin and skin structure infections in the United States.

Objectives: We estimated the total US hospital costs associated with acute bacterial skin and skin structure infection (ABSSSI) admissions as well as the admissions that may have been potential candidates for outpatient parenteral antimicrobial therapy (OPAT). Methods: We assessed inpatient admissions for ABSSSI from the Premier database (2011-2014), focusing on all admissions of adults with length of stay (LOS) ≥ 1 days and a primary diagnosis of erysipelas, cellulitis/abscess, or wound infection. We performed a detailed analysis of 2014 admissions for patient, treatment, hospital, and economic characteristic variables. Using published selection criteria, we identified a subset of patients admitted in 2014 who may have been potential candidates for OPAT. Results: We analyzed 277,971 admissions. In 2014, most admissions were for cellulitis without major complications or comorbidities; mean ± SD LOS was 4.0 ± 3.0 days, and total hospital cost per admission was $6400 ± $6874, 54% of which was attributable to room costs. Among 2014 admissions, 14% involved patients with clinical characteristics suggesting that they were consistent with guideline recommendations for exclusive treatment with OPAT. Compared with all admissions in the year, these admissions were of younger patients (aged 50 vs. 55 years), admitted more frequently for cellulitis (90% vs. 70%), with shorter LOS (2.8 ± 1.8 days), and lower mean total hospital cost per admission ($4080 ± $3066). Conclusions: Admissions for ABSSSI impose a substantial cost to US hospitals, with half of costs attributable to room costs. When extrapolated to all US patients admitted to the hospital for ABSSSI during 2014, had OPAT guidelines been universally followed, admissions may have been reduced by 14%, thereby saving US hospitals $161 million.

Real-World Clinical Effectiveness and Cost Savings of Liraglutide Versus Sitagliptin in Treating Type 2 Diabetes for 1 and 2 Years.

INTRODUCTION: This study compared the clinical and economic outcomes of long-term use of liraglutide versus sitagliptin for the treatment of type 2 diabetes (T2DM) in real-world practice in the USA. METHODS: We identified adult patients (≥ 18 years old) with T2DM who initiated liraglutide or sitagliptin in 2010-2014 using a large claims database. Quarterly glycemic control measures and annual healthcare costs were assessed during the 1st and 2nd years of persistent medication use. Their associations with medication use (liraglutide or sitagliptin) were estimated using multivariable regression models adjusted for patient demographic and clinical characteristics. RESULTS: A total of 3113 patients persistently used liraglutide (N = 493) or sitagliptin (N = 2620) for ≥ 1 year [mean age (standard deviation, SD): 53 (8.5) vs. 56 (9.7) years; 48.3% vs. 62.3% males; both p < 0.05]; 911 (including 113 liraglutide users) were persistent users for ≥ 2 years. During the 1st-year follow-up, liraglutide users (versus sitagliptin users, after adjustment) experienced larger glycated hemoglobin (HbA1c) reductions from baseline (ranging from 0.34%-point in quarter 1 to 0.21%-point in quarter 4); higher likelihoods of obtaining HbA1c reductions of ≥ 1%-points or ≥ 2%-points [odds ratios (ORs) range 1.47-2.04]; and higher likelihoods of reaching HbA1c goals of < 6.5% or < 7% (ORs range 1.51-2.12) (all p < 0.05). Liraglutide users also experienced HbA1c reductions from baseline in the 2nd-year follow-up (0.53-0.33%-point, all p < 0.05). Although liraglutide users incurred higher healthcare costs than sitagliptin users during the 1st-year follow-up, they had $2674 (per patient) lower all-cause medical costs (adjusted cost ratio: 0.67, p < 0.05) and similar total costs (all-cause and diabetes-related) in the 2nd year. CONCLUSION: Long-term use of liraglutide for 1 or 2 years was associated with better glycemic control than using sitagliptin. Savings in medical costs were realized for liraglutide users during the 2nd year of persistent treatment, which offset differences in pharmacy costs. FUNDING: Novo Nordisk Inc.

The burden of severe hypoglycemia in type 2 diabetes.

AIMS: More than 29 million people in the US have type 2 diabetes mellitus (T2DM), a chronic metabolic disorder characterized by a progressive deterioration of glucose control, which eventually requires insulin. Abnormally low levels of blood glucose, a feared side-effect of insulin treatment, may cause severe hypoglycemia (SHO), leading to emergency department (ED) admission, hospitalization, and long-term complications; these, in turn, drive up the costs of T2DM. This study's objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T2DM using insulin. METHODS: Using Truven MarketScan claims, we identified adult T2DM patients using basal and basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010-2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including ED visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated, and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts. RESULTS: We identified 66,179 patients using basal and 81,876 patients using basal-bolus insulin, of which ∼1.1% (basal) to 3.2% (basal-bolus) experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. those in the inpatient and outpatient SHO groups), 27% (basal) and 40% (basal-bolus) experienced at least one SHO-related hospitalization. One-third of basal and about one-quarter of basal-bolus patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. Inpatient SHO patients using basal insulin stayed in the hospital, including time in the ED, for 2.8 days and incurred $6896 in costs; patients using basal-bolus insulin stayed in the hospital for 2.6 days and incurred costs of $5802. Forty-to-fifty percent of inpatient SHO patients were hospitalized again for SHO. Inpatient SHO patients using basal insulin incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the other two groups ($2935 vs $1819 and $1638), corresponding to 61% and 79% higher monthly costs; patients using basal-bolus insulin also incurred significantly higher monthly costs than patients in the other groups ($3606 vs $2731 and $2607), corresponding to 32% and 38% higher monthly costs. LIMITATIONS: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders. CONCLUSIONS: The burden associated with SHO is not negligible. Nearly one in three patients using only basal insulin and one in four patients using basal-bolus regimens who experienced SHO were hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incurred at least $1,116 (62%) and $875 (70%) more per month than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T2DM.

The burden of severe hypoglycemia in type 1 diabetes.

AIMS: Approximately 1.25 million people in the US have type 1 diabetes mellitus (T1DM), a chronic metabolic disease that develops from the body's inability to produce insulin, and requires life-long insulin therapy. Poor insulin adherence may cause severe hypoglycemia (SHO), leading to hospitalization and long-term complications; these, in turn, drive up costs of SHO and T1DM overall. This study's objective was to estimate the prevalence and costs of SHO-related hospitalizations and their additional longer-term impacts on patients with T1DM using basal-bolus insulin. METHODS: Using Truven MarketScan claims, we identified adult T1DM patients using basal-bolus insulin regimens who were hospitalized for SHO (inpatient SHO patients) during 2010-2015. Two comparison groups were defined: those with outpatient SHO-related encounters only, including emergency department (ED) visits without hospitalization (outpatient SHO patients), and those with no SHO- or acute hyperglycemia-related events (comparison patients). Lengths of stay and SHO-related hospitalization costs were estimated and propensity score and inverse probability weighting methods were used to adjust for baseline differences across the groups to evaluate longer-term impacts. RESULTS: We identified 8,734 patients, of which 4.2% experienced at least one SHO-related hospitalization. Among those who experienced SHO (i.e. of those in the inpatient and outpatient SHO groups), 31% experienced at least one SHO-related hospitalization, while 9% were treated in the ED without subsequent hospitalization. Approximately 79% of patients were admitted directly to the hospital; the remainder were first assessed or treated in the ED. The inpatient SHO patients stayed in the hospital, including time in the ED, for 1.7 days and incurred $3551 in costs. About one-third of patients were hospitalized again for SHO. Inpatient SHO patients incurred significantly higher monthly costs after their initial SHO-related hospitalization than patients in the two other groups ($2084 vs $1313 and $1372), corresponding to 59% or 52% higher monthly costs for inpatient SHO patients. LIMITATIONS: These analyses excluded patients who did not seek ED or hospital care when faced with SHO; events may have been miscoded; and we were not able to account for clinical characteristics associated with SHO, such as insulin dose and duration of diabetes, or unmeasured confounders. CONCLUSIONS: The burden associated with SHO is not negligible. About 4% of T1DM patients using basal-bolus insulin regimens are hospitalized at least once due to SHO. Not only did those patients incur the costs of their SHO hospitalization, but they also incur red at least $712 (52%) more in costs per month after their hospitalization than outpatient SHO or comparison patients. Reducing SHO events can help decrease the burden associated with SHO among patients with T1DM.

Comparing Healthcare Costs Associated with Oral and Subcutaneous Methotrexate or Biologic Therapy for Rheumatoid Arthritis in the United States.

BACKGROUND: Methotrexate (MTX) is the primary disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Optimizing the use of oral and subcutaneous MTX may delay the use of expensive biologic therapies; the effect of such a delay on overall medical costs is currently unknown. OBJECTIVE: To compare the 5-year healthcare costs of treatment pathways for patients with RA who initiate oral MTX in the United States. METHODS: We identified patients with RA in the Symphony Health Solutions database (Integrated Dataverse) who initiated treatment with oral MTX in 2009 and had RA-related claims for each year through 2014. We then grouped the patients into 4 treatment cohorts, including those who (1) continued to use oral MTX, (2) switched to subcutaneous MTX, (3) switched to subcutaneous MTX and then added or switched to a biologic therapy, and (4) added or switched to a biologic therapy. The costs (in 2015 US dollars) for pharmaceuticals, office visits, hospitalizations, and emergency department visits were estimated for each cohort. RESULTS: Of the total 35,640 patients in this study, 15,599 patients continued to use oral MTX, with an average cost of $47,464 per patient in the full study period; 1802 patients switched to subcutaneous MTX, with an average per-patient cost of $59,058; 711 patients switched to subcutaneous MTX and then added or switched to a biologic agent, with an average per-patient cost of $175,391 and a mean time to a biologic use of 1184 days; and 17,528 patients added or switched to a biologic from oral MTX, with an average per-patient cost of $212,595 and a mean time to a biologic use of 478 days. Biologic treatments were responsible for the cost differences between the cohorts; the nondrug costs were similar across the groups. CONCLUSION: Our findings that patients who switched to subcutaneous MTX incurred lower costs than patients who only used oral MTX before using biologics may provide useful information for patients and providers who are choosing between continued MTX use and adding or switching to a biologic based on treatment guidelines.