Impact of Elexacaftor/Tezacaftor/Ivacaftor on Healthcare Resource Utilization and Associated Costs Among People With Cystic Fibrosis in the US: A Retrospective Claims Analysis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US. METHODS: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. RESULTS: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. CONCLUSIONS: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

Disease burden in people with cystic fibrosis heterozygous for F508del and a minimal function mutation.

BACKGROUND: People with cystic fibrosis (CF) heterozygous for F508del-CFTR and a minimal function CFTR mutation (F/MF) that results in no CFTR protein or results in CFTR protein that is not responsive to tezacaftor, ivacaftor, and tezacaftor/ivacaftor in vitro comprise a sizeable percentage of the US CF population. This retrospective, cross-sectional, observational study aimed to characterize CF burden in this subpopulation. METHODS: People ≥2 years of age in the US CF Foundation Patient Registry with a CF diagnosis, F/MF genotype, and ≥1 encounters in 2017 were included. Descriptive analyses assessed lung function, nutritional parameters, microbiology, hospitalization and pulmonary exacerbation rates, and CF-related complications. Results were stratified by age group; select characteristics were summarized by percent predicted FEV1 (ppFEV1) and ethnicity. RESULTS: 5348 people met inclusion criteria. Rates of positive bacterial cultures, pulmonary exacerbations, and hospitalizations were generally higher in older age groups. Prevalence of prescribed symptomatic CF therapies was substantial and also generally higher in older age groups. ppFEV1 was lower in older age groups. A greater percentage of adolescents and adults reported complications, including cirrhosis, osteoporosis, osteopenia, and sinus disease, than younger age groups. Increased prevalence of cultured Pseudomonas aeruginosa and prescribed chronic therapy was seen with decreasing ppFEV1. In each age group, ppFEV1 was slightly higher in the non-Hispanic cohort than in the Hispanic cohort. CONCLUSIONS: People with F/MF genotypes have substantial disease burden that worsened in older age groups consistent with the progressive nature of CF, indicating need for additional treatment options in this subpopulation.

Treating Type 1 Diabetes Mellitus with a Rapid-Acting Analog Insulin Regimen vs. Regular Human Insulin in Germany: A Long-Term Cost-Effectiveness Evaluation.

OBJECTIVE: The aim of the present study was to evaluate the cost effectiveness of rapid-acting analog insulin relative to regular human insulin in adults with type 1 diabetes mellitus in Germany. METHODS: The PRIME Diabetes Model, a patient-level, discrete event simulation model, was used to project long-term clinical and cost outcomes for patients with type 1 diabetes from the perspective of a German healthcare payer. Simulated patients had a mean age of 21.5 years, duration of diabetes of 8.6 years, and baseline glycosylated hemoglobin of 7.39%. Regular human insulin and rapid-acting analog insulin regimens reduced glycosylated hemoglobin by 0.312 and 0.402%, respectively. Compared with human insulin, hypoglycemia rate ratios with rapid-acting analog insulin were 0.51 (non-severe nocturnal) and 0.80 (severe). No differences in non-severe diurnal hypoglycemia were modeled. Discount rates of 3% were applied to future costs and clinical benefits accrued over the 50-year time horizon. RESULTS: In the base-case analysis, rapid-acting analog insulin was associated with an improvement in quality-adjusted life expectancy of 1.01 quality-adjusted life-years per patient (12.54 vs. 11.53 quality-adjusted life-years). Rapid-acting analog insulin was also associated with an increase in direct costs of €4490, resulting in an incremental cost-effectiveness ratio of €4427 per quality-adjusted life-year gained vs. human insulin. Sensitivity analyses showed that the base case was driven predominantly by differences in hypoglycemia; abolishing these differences reduced incremental quality-adjusted life expectancy to 0.07 quality-adjusted life-years, yielding an incremental cost-effectiveness ratio of €74,622 per quality-adjusted life-year gained. CONCLUSIONS: Rapid-acting analog insulin is associated with beneficial outcomes in patients with type 1 diabetes and is likely to be considered cost effective in the German setting vs. regular human insulin.

Insulin dosing and outcomes among commercially insured patients with type 2 diabetes in the United States.

PURPOSE: The purpose of this study was to examine costs, resource use, adherence, and hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) treated with increasing doses of 100-U/mL (U-100) insulin regimens. METHODS: Data from Truven's Health Analytics Commercial Claims and Encounters database from January 1, 2008, through January 31, 2011, were used. Regressions were used to examine the associations among costs, resource use, adherence, and receipt of a hypoglycemic event and index dose of insulin. Specifically, general linear models with a γ-distribution and log link were used to examine costs, whereas logistic and negative binomial regressions were used to examine resource use and hypoglycemic events. All analyses controlled for patient characteristics, preindex comorbidities, general health, use of antidiabetic medications, and visits to an endocrinologist. FINDINGS: The study focused on 101,728 individuals with T2DM who received an outpatient prescription for U-100 insulin. In general, costs and resource use are highest among patients treated with the highest dose of insulin (>300 U/d). For example, all-cause and diabetes-related hospitalizations and office visits were highest in the highest-dose cohort. Costs generally followed the same pattern. Patients who were prescribed the lowest dose of insulin (10-100 U/d) generally had higher all-cause or diabetes-related inpatient and emergency department costs and resource use compared with those patients with an index dose >100 to 150, >150 to 200, and >200 to 300 U/d. There were generally no significant differences in rates of hypoglycemic events based on index dose. IMPLICATIONS: These results suggest significant differences in patient outcomes based on dosing of insulin. Those patients with T2DM using insulin at the highest and lowest dose ranges have the highest costs and resource use.

Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes.

OBJECTIVE: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years) diagnosed with diabetes. METHODS: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin. RESULTS: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10-100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10-100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100-150 units/day were significantly more likely to experience a hypoglycemic event. CONCLUSION: These results suggest that, for elderly individuals with diabetes, there is a higher patient burden among those who receive the lowest and highest insulin doses.

Health state utilities for skeletal-related events secondary to bone metastases.

INTRODUCTION: Patients with bone metastases often experience skeletal-related events (SREs). Although cost-utility models are used to examine treatments for metastatic cancer, limited information is available on utilities of SREs. The purpose of this study was to estimate the disutility of four SREs: spinal cord compression, pathological fracture, radiation to bone, and surgery performed to stabilize a bone. METHODS: General population participants from the UK and Canada completed time trade-off (TTO) interviews to assess the utility of health states drafted based on literature review, clinician interviews, and patient interviews. Respondents first rated a health state describing cancer with bone metastases. Then, the SREs were added to this health state. RESULTS: Interviews were completed with 187 participants (50.8 % male, 80.2 % white). Cancer with bone metastases without an SRE had a mean utility of 0.47 (SD = 0.43) on a standard utility scale (1 = full health, 0 = death). Of the SREs, spinal cord compression was associated with the greatest disutility (i.e., the utility decrease): -0.32 with paralysis and -0.22 without paralysis. Surgery had a disutility of -0.07. Leg, arm, and rib fractures had disutilities of -0.06, -0.04, and -0.03. Two weeks of daily radiation treatment had a disutility of -0.06, while two radiation appointments had the smallest impact on utility (-0.02). CONCLUSION: All SREs were associated with statistically significant utility decreases, suggesting a perceived impact on quality of life beyond the impact of cancer with bone metastases. The resulting disutilities may be used in cost-utility models examining treatments to prevent SREs secondary to bone metastases.

Insulin use in long term care settings for patients with type 2 diabetes mellitus: a systematic review of the literature.

OBJECTIVE: To summarize currently available data about insulin therapy in patients with diabetes mellitus (DM), focusing on patients with type 2 DM (T2DM), in long term care (LTC) settings. DATA SOURCES: Ovid Medline, EMBASE, Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database, last accessed on November 12, 2012. STUDY ELIGIBILITY CRITERIA: We included studies that reported insulin use in patients with T2DM, and studies with combined samples of patients with type 1 DM or T2DM, that were conducted in LTC settings. Excluded were review articles and studies published before 2000. RESULTS: We identified 11 articles that met all inclusion and exclusion criteria. Insulin use in patients with DM in LTC settings varied widely, from 2.7% to 58.0%. It is difficult to draw conclusions from these proportions, as many studies did not define whether their populations were exclusively patients with T2DM. Despite recommendations against its use by the American Diabetes Association, the American Geriatrics Society, and the American Medical Directors Association, treatment with sliding-scale insulin (insulin injections adjusted to current blood glucose levels) was prevalent in the LTC setting. Although the recommended target hemoglobin A1c (A1C) for this patient population varies from ≤6.5% to ≤8.0%, higher A1C values (8.0%-8.9%) were associated with better patient outcomes in a study examining insulin treatment in community-dwelling elderly patients enrolled in an outpatient LTC setting. Insulin pen-devices seemed associated with a high incidence of needle-stick injuries in workers in LTC settings but, compared with insulin vials, showed cost advantages for use in very short-term (≤30 days) patients with DM in LTC settings. LIMITATIONS: Paucity of available data; only published studies for which full-text articles could be retrieved and which were identified by our search strategy were included; insufficient detail about patient samples were available in many included studies; and potential biases across studies might be introduced by funding sources or study designs. CONCLUSIONS: Available data about insulin therapy in patients with DM in LTC settings are very scarce and great treatment variability of this patient population seems to prevail in the current clinical practice. Additional, randomized, prospective clinical trials are needed to expand our knowledge and allow clinicians to make informed treatment decisions for patients with DM in LTC settings.