Real-world rates,predictors, and associated costs of hypoglycemia among patients with type 2 diabetes mellitus treated with insulin glargine: results of a pooled analysis of six retrospective observational studies

Abstract

Objective:

To evaluate the real-world rates of hypoglycemia and related costs among patients with type 2 diabetes mellitus (T2DM) who initiated insulin glargine with either a disposable pen or vial-and-syringe.

Methods:

Pooled data were evaluated from six previously published, retrospective, observational studies using US health plan insurance claims databases to investigate adults with T2DM who initiated insulin glargine. The current study evaluated baseline characteristics, hypoglycemic events, and costs during the 6 months prior to and 12 months following insulin glargine initiation. Comparisons were made between patients initiating treatment with a disposable pen (GLA-P) and vial-and-syringe (GLA-V). Multivariate analyses using baseline characteristics as covariates determined predictors of hypoglycemia after initiating insulin glargine.

Results:

This study included 23,098 patients (GLA-P: 14,911; GLA-V: 8187). Overall annual prevalence of hypoglycemia was low (6.3% overall, 2.2% related to hospital admission or emergency department visit). Prevalence was significantly lower with GLA-P (5.5% vs 7.7%; p?<?0.0001). Furthermore, average glycated hemoglobin HbA1c reduction was higher with GLA-P (?1.22% vs ?0.86%; p?=?0.0012). The average annual hypoglycemia-related cost associated with initiating insulin glargine was $293, with GLA-P being 46% lower than GLA-V ($225 vs $417; p?=?0.001). Patients who had already developed microvascular complications at the time of initiating insulin therapy were at higher risk for developing hypoglycemia.

Limitations:

This study is limited by the use of retrospective data and ICD-9-CM codes, which are subject to coding error. In addition, this pooled analysis used unmatched cohorts, with multivariate regression analyses employed to adjust for between-group differences. Finally, results describe a managed care sample and cannot be generalized to all patients with T2DM.

Conclusions:

Patients with T2DM initiating insulin glargine treatment showed low rates of hypoglycemia, especially when using a disposable pen device. Hypoglycemia-related costs were low, contributing a very small proportion to overall diabetes-related healthcare costs.     

Comparison of utilization,cost, adherence,and hypoglycemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/syringe

Abstract

Background:

Studies examining outcomes of different insulin delivery systems are limited. The objective of this study was to compare healthcare utilization, costs, adherence, and hypoglycemia rates in patients with type 2 diabetes mellitus (T2DM) initiating rapid-acting insulin analog (RAIA) using prefilled pen versus vial/syringe.

Methods:

A retrospective analysis was conducted using a US claims database (1/1/2007 to 12/31/2008). Inclusion criteria were: ≥18 years old, with T2DM, ≥12 months of continuous eligibility, and new to RAIA. Difference-in-difference analyses after propensity score matching were conducted to compare changes in outcomes from 6 months prior to and 6 months after initiating RAIA with a prefilled pen versus vial/syringe (Wilcoxon rank-sum test for costs and t-test for other outcomes). Categories of utilization and costs (2009 USD) included total and diabetes-related inpatient, outpatient, and emergency room. Adherence was measured by proportion of days covered (PDC). Hypoglycemia was identified using ICD-9-CM codes.

Results:

Baseline characteristics were similar between the prefilled pen (n?=?239) and vial/syringe (n?=?590) cohorts after matching. Adherence to RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (PDC: 54.6 vs. 45.2%, p?<?0.001). While the increase in diabetes-related pharmacy costs from before to after initiating RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (+$900 vs. +$607, p?<?0.001), the prefilled pen cohort was associated with greater reductions in the total diabetes-related costs (–$235 vs. +$61, p?=?0.006) and the utilization of oral anti-hyperglycemic agents (–1.3 vs. –0.7, p?=?0.016). There were no significant differences in other outcomes.

Limitations:

Claims databases do not provide optimal measures for adherence or T2DM severity, and only capture hypoglycemia events requiring clinical intervention.

Conclusion:

Initiating RAIA with a prefilled pen was associated with better adherence and greater reduction in total diabetes-related costs than a vial/syringe. There was no significant difference in total healthcare costs.     

Economic outcomes with the conversion of insulin delivery methods in hospitals

Purpose: To evaluate the insulin wastage and associated acquisition costs when switching from individual patient supply (IPS) of 3-mL pens of rapid-acting insulin (RAI) aspart to floor stock (FS) dispensing of 3-mL vials of RAI lispro, and with conversion from IPS of 3-mL pens to centralized unit dose (CUD) of 10-mL vials of basal insulin detemir.

Methods: Data from September 2010 to December 2012 from three hospitals in the Roper St. Francis Healthcare (RSFH) were used: Roper Hospital (368 beds), Bon Secours St. Francis Hospital (204 beds), and Roper St. Francis Mt. Pleasant Hospital (85 beds). Insulin wastage and associated acquisition costs were estimated using regression models.

Results: The conversion from IPS of 3-mL pens of insulin aspart to FS of 3-mL vials of lispro was associated with a significant decrease in insulin wastage (204,042 IUs; p?p?p?p?Conclusions: Switching RAI from IPS of 3-mL pens of insulin aspart to one-time unit dose insulin lispro dispensed from FS 3-mL vials as needed significantly reduced insulin wastage and associated acquisition costs at the three combined hospitals. Conversion of basal insulin from IPS of 3-mL pens of insulin detemir to CUD of 10-mL vials of insulin detemir was associated with a significant reduction in insulin wastage and associated acquisition costs at three hospitals combined.     

Resource utilization and healthcare costs for acute coronary syndrome patients with and without diabetes mellitus

Abstract

Objective:

This study compared differences in healthcare costs and resource utilization for acute coronary syndrome (ACS) patients with and without diabetes mellitus (DM).

Methods:

A retrospective cohort study of a large, US employer-based claims database identified adults hospitalized for ACS between 01/01/2005 and 12/31/2006 and categorized them based on DM status. Resource utilization and costs during the index hospitalization and in the 12-month follow-up period were compared for ACS patients with and without DM using the propensity score stratification bootstrapping method, adjusting for differences in demographic and clinical characteristics.

Results:

Of 12,502 patients who met selection criteria, 3,040 (24%) had a history of DM and 9,462 (76%) did not. Patients with DM were older, female, and had higher rates of previous cardiovascular and renal diseases. After the propensity score stratification, patients with DM incurred higher index hospitalization costs ($32,577 vs. $29,150, p?<?0.01) as well as higher total follow-up healthcare costs ($35,400 vs. $24,080, p?<?0.01), including higher inpatient ($17,278 vs. $11,247, p?<?0.01), outpatient ($12,357 vs. $8,853, p?<?0.01), and pharmacy costs ($5,765 vs. $3,980, p?<?0.01).

Limitations:

General limitations exist with any retrospective claims database analysis including potential diagnostic or procedural coding inaccuracies. Additionally, the patient population was representative of a working-age population with employer-sponsored health insurance and results may not be generalizable to other patient populations.

Conclusions:

DM is significantly associated with increased healthcare resource utilization and costs for ACS patients.     

Clinical comorbidities,treatment patterns,and healthcare costs among patients with fibromyalgia newly prescribed pregabalin or duloxetine in usual care

Abstract

Objective:

To assess comorbidities, pain-related pharmacotherapy, and healthcare resource use among patients with fibromyalgia (FM) newly prescribed pregabalin or duloxetine (index event) in usual care settings.

Methods:

Using the LifeLink? Health Plan Claims Database, patients with FM (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1X) were identified. Patients initiated on duloxetine were propensity score-matched with patients initiated on pregabalin (n?=?826; mean age [standard deviation] of 48.3 [9.3] years for both groups). Prevalence of comorbidities, pain-related pharmacotherapy, and healthcare resource use/costs were examined during the 12-month pre-index and follow-up periods.

Results:

Both patient groups had multiple comorbidities and a substantial pain-related and adjuvant medication burden. In the pregabalin group, use of other anticonvulsants decreased significantly (31.6% vs 24.9%), whereas use of serotonin-norepinephrine reuptake inhibitors (SNRIs; 16.5% vs 22.5%) and topical agents (10.1% vs 13.2%) increased in the follow-up period (p?<?0.01). In the duloxetine group, there were significant decreases in the use of other SNRIs (13.0% vs 5.7%), selective serotonin reuptake inhibitors (41.3% vs 21.7%), and tricyclic antidepressants (18.8% vs 13.2%), and an increase in the use of anticonvulsants (28.6% vs 40.1%; p?<?0.0001). There were significant increases (p?<?0.0001) in pharmacy and total healthcare costs in both cohorts, and a significant increase in outpatient costs (p?=?0.0084) in the duloxetine cohort from pre-index to follow-up. There were no significant differences in median total healthcare costs between the pregabalin and duloxetine groups in both the pre-index ($10,159 vs $9,556) and follow-up ($11,390 vs $11,746) periods.

Limitations:

Limitations of this study are typical of those associated with retrospective database analyses.

Conclusions:

Patients with FM prescribed pregabalin or duloxetine were characterized by a significant comorbidity and pain/adjuvant medication burden. Although healthcare costs increased in both groups, there were no statistically significant differences in direct healthcare costs between the two groups.     

Healthcare costs,treatment patterns,and resource utilization among pancreatic cancer patients in a managed care population

Abstract

Background:

Pancreatic adenocarcinoma has few effective treatment options and poor survival. The objective of this study was to characterize treatment patterns and estimate the costs and resource use associated with its treatment in a commercially-insured US population.

Methods:

In this retrospective claims-based analysis, individuals ≥18 years old with evidence of pancreatic adenocarcinoma between January 1, 2001 and December 31, 2010 were selected from a managed care database. Treatment phase (either initial non-metastatic or metastatic) was determined using a claims-based algorithm. Patients in the pancreatic cancer population were matched 1:3 to a control population. Resource use (events/person-years), treatment patterns, and healthcare costs (per-patient per-month, PPPM) were determined during a variable length follow-up period (from first pancreatic cancer diagnosis to earliest of death, disenrollment, or study end).

Results:

In this study, 5262 pancreatic cancer patients were matched to 15,786 controls. Rates of office visits, inpatient visits, ER visits, and inpatient stays, and mean total all-cause healthcare costs PPPM ($15,480 vs $1001) were significantly higher among cancer patients than controls (all p?<?0.001). Mean inpatient costs were the single largest cost driver ($9917 PPPM). Also, mean total all-cause healthcare costs were significantly higher during the metastatic treatment phase vs the initial treatment phase of non-metastatic disease ($21,637 vs $10,358, p?<?0.001).

Conclusions:

These results indicate that pancreatic cancer imposes a substantial burden on the US healthcare system, and that treatment of more advanced disease is significantly more costly than initial treatment of non-metastatic disease.

Limitations:

Additional research is needed to validate the accuracy of the claims-based algorithms used to identify the treatment phase.     

Comparison of medical costs and healthcare resource utilization of post-menopausal women with HR+/HER2− metastatic breast cancer receiving everolimus-based therapy or chemotherapy: a retrospective claims database analysis

Objective:

To analyze medical costs and healthcare resource utilization (HRU) associated with everolimus-based therapy or chemotherapy among post-menopausal women with hormone-receptor-positive, human-epidermal-growth-factor-receptor-2-negative (HR+/HER2?) metastatic breast cancer (mBC).

Methods:

Patients with HR+/HER2? mBC who discontinued a non-steroidal aromatase inhibitor and began a new line of treatment with everolimus-based therapy or chemotherapy (index therapy/index date) between July 20, 2012 and April 30, 2014 were identified from two large claims databases. All-cause, BC-related, and adverse event (AE)-related medical costs (in 2014 USD) and all-cause HRU per patient per month (PPPM) were analyzed for both treatment groups across patients’ first four lines of therapies for mBC. Adjusted differences in costs and HRU between the everolimus and chemotherapy treatment group were estimated pooling all lines and using multivariable generalized linear models, accounting for difference in patient characteristics.

Results:

A total of 3298 patients were included: 902 everolimus-treated patients and 2636 chemotherapy-treated patients. Compared to chemotherapy, everolimus was associated with significantly lower all-cause (adjusted mean difference?=?$3455, p?<?0.01) and BC-related ($2510, p?<?0.01) total medical costs, with inpatient ($1344, p?<?0.01) and outpatient costs ($1048, p?<?0.01) as the main drivers for cost differences. Everolimus was also associated with significantly lower AE-related medical costs ($1730, p?<?0.01), as well as significantly lower HRU (emergency room incidence rate ratio [IRR]?=?0.83; inpatient IRR?=?0.74; inpatient days IRR?=?0.65; outpatient IRR?=?0.71; BC-related outpatient IRR?=?0.57; all p?<?0.01).

Conclusions:

This retrospective claims database analysis of commercially-insured patients with HR+/HER2? mBC in the US showed that everolimus was associated with substantial all-cause, BC-related, and AE-related medical cost savings and less utilization of healthcare resources relative to chemotherapy.     

Real-world treatment patterns and healthcare costs among biologic-naive patients initiating apremilast or biologics for the treatment of psoriasis

Objective: This study compared real-world treatment patterns and healthcare costs among biologic-naive psoriasis patients initiating apremilast or biologics.

Methods: A retrospective cohort study was conducted using the Optum Clinformatics? claims database. Patients with psoriasis were selected if they had initiated apremilast or biologics between January 1, 2014, and December 31, 2015; had 12?months of pre-index and post-index continuous enrollment in the database; and were biologic-naive. The index date was defined as the date of the first claim for apremilast or biologic, and occurred between January 1, 2014, and December 31, 2015. Treatment persistence was defined as continuous treatment without a?>?60-day gap in therapy (discontinuation) or a switch to a different psoriasis treatment during the 12-month post-index period. Adherence was defined as a medication possession ratio (MPR) of ≥ 80% while persistent on the index treatment. Persistence-based MPR was defined as the number of days with the medication on hand measured during the patients’ period of treatment persistence divided by the duration of the period of treatment persistence. Because patients were not randomized, apremilast patients were propensity score matched up to 1:2 to biologic patients to adjust for possible selection bias. Treatment persistence/adherence and all-cause healthcare costs were evaluated. Cost differences were determined using Wilcoxon rank-sum tests.

Results: In all, 343 biologic-naive patients initiating apremilast were matched to 680 biologic-naive patients initiating biologics. After matching, patient characteristics were similar between cohorts. Twelve-month treatment persistence was similar for biologic-naive patients initiating apremilast vs biologics (32.1% vs 33.2%; p?=?0.7079). While persistent on therapy up to 12?months, per-patient per-month (PPPM) total healthcare costs were significantly lower among biologic-naive cohorts initiating apremilast vs biologics ($2,214 vs $5,184; p?p?p?p?Limitations: Data were limited to individuals with United Healthcare commercial and Medicare Advantage insurance plans, and may not be generalizable to psoriasis patients with other insurance or without health insurance coverage.

Conclusion: Biologic-naive patients with similar patient characteristics receiving apremilast vs biologics had significantly lower PPPM costs, even when they switched to biologics during the 12-month post-index period. These results may be useful to payers and providers seeking to optimize psoriasis care while reducing healthcare costs.     

Healthcare utilization changes in relation to treatment intensification with insulin aspart in patients with type 2 diabetes. Data from a large US managed-care organization

ABSTRACT

Objective: Most patients with type 2 diabetes eventually require exogenous insulin therapy to achieve good glycemic control due to the progressive nature of the disease. Insulin aspart is a rapid-acting insulin analog developed for prandial use. This study aimed to illustrate the implications on healthcare costs of adding insulin aspart to basal therapy in a real-world setting.

Methods: Patients with type 2 diabetes who intensified previous basal therapy with insulin aspart were identified from a large commercial US healthcare data source between April 2007 and September 2008. Patients were required to have received basal insulin treatment with or without concomitant oral antidiabetic (OAD) therapy for at least 90 days pre- and post-initiation of insulin aspart. Wilcoxon signed-rank test and McNemar's test were used for continuous and categorical variables, respectively, to analyze the difference of self-comparison between pre- and post insulin aspart add-on.

Results: In total, 1,739 patients with an average age of 56 years were identified, of whom 55% were male. After initiation of insulin aspart, a significant improvement in glycemic control was observed (change in HbA_1c: –0.5%, p=0.0013). Similarly, a reduction of 0.4% in HbA_1c was observed for the subpopulation of 151 patients, who had both pre-and post-index HbA_1c data (p=0.0085). Also, significantly fewer patients used OADs after insulin aspart initiation (56 vs. 64%, p< 0.0001). Overall and diabetes-related healthcare costs also significantly decreased by $2,283 and $2,028, respectively (p≤0.0001). Diabetes-related inpatient visits appear to be the main contributor to total cost (46%); however, after initiation of insulin aspart the number of inpatient visits decreased by 0.50 visits/patient/year (p< 0.05). This decrease was reflected in a large reduction in cost related to inpatient visits ($3,019/patient).

Limitations: A regression to the mean effect may be associated with this pre-post comparison. The ability to make conclusions regarding cause and effect may be limited due to the retrospective design of this study.

Conclusions: Patients with type 2 diabetes achieved better glycemic control and needed less OAD treatment after adding insulin aspart to previous basal therapy. Furthermore, patients experienced on average reduced healthcare utilization after initiation of insulin aspart, which resulted in significant cost savings.     

Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population

Aims: To examine the comorbidity and economic burden among moderate-to-severe psoriasis (PsO) and/or psoriatic arthritis (PsA) patients in the US Department of Defense (DoD) population.

Materials and methods: This retrospective cohort claims analysis was conducted using DoD data from November 2010 to October 2015. Adult patients with ≥2 diagnoses of PsO and/or PsA (cases) were identified, and the first diagnosis date from November 2011 to October 2014 was defined as the index date. Patients were considered moderate-to-severe if they had ≥1 non-topical systemic therapy or phototherapy during the 12 months pre- or 1 month post-index date. Patients without a PsO/PsA diagnosis during the study period (controls) were matched to cases on a 10:1 ratio based on age, sex, region, and index year; the index date was randomly selected. One-to-one propensity score matching (PSM) was conducted to compare study outcomes in the first year post-index date, including healthcare resource utilization (HRU), costs, and comorbidity incidence.

Results: A total of 7,249 cases and 72,490 controls were identified. The mean age was 48.1 years. After PSM, comorbidity incidence was higher among cases, namely dyslipidemia (18.3% vs 13.5%, p?<?.001), hypertension (13.8% vs 8.7%, p?<?.001), and obesity (8.8% vs 6.1%, p?<?.001). Case patients had significantly higher HRU and costs, including inpatient ($2,196 vs $1,642; p?<?.0016), ambulatory ($8,804 vs 4,642; p?<?.001), emergency room ($432 vs $350; p?<?.001), pharmacy ($6,878 vs $1,160; p?<?.001), and total healthcare costs ($18,311 vs $7,795; p?<?.001).

Limitations: Claims data are collected for payment purposes; therefore, such data may have limitations for clinical research.

Conclusions: During follow-up, DoD patients with moderate-to-severe PsO and/or PsA experienced significantly higher HRU, cost, and comorbidity burden.     

Healthcare utilization and costs associated with COPD among SEER-Medicare beneficiaries with NSCLC

Aim: To estimate the healthcare utilization and costs in elderly lung cancer patients with and without pre-existing chronic obstructive pulmonary disease (COPD).

Methods: Using Surveillance, Epidemiology and End Results (SEER)-Medicare data, this study identified patients with lung cancer between 2006–2010, at least 66 years of age, and continuously enrolled in Medicare Parts A and B in the 12 months prior to cancer diagnosis. The diagnosis of pre-existing COPD in lung cancer patients was identified using ICD-9 codes. Healthcare utilization and costs were categorized as inpatient hospitalizations, skilled nursing facility (SNF) use, physician office visits, ER visits, and outpatient encounters for every stage of lung cancer. The adjusted analysis was performed using a generalized linear model for healthcare costs and a negative binomial model for healthcare utilization.

Results: Inpatient admissions in the COPD group increased for each stage of non-small cell lung cancer (NSCLC) compared to the non-COPD group per 100 person-months (Stage I: 14.67 vs 9.49 stays, p?<?.0001; Stage II: 14.13 vs 10.78 stays, p?<?.0001; Stage III: 28.31 vs 18.91 stays, p?<?.0001; Stage IV: 49.5 vs 31.24 stays, p?<?.0001). A similar trend was observed for outpatient visits, with an increase in utilization among the COPD group (Stage I: 1136.04 vs 796 visits, p?<?.0001; Stage II: 1325.12 vs 983.26 visits, p?<?.0001; Stage III: 2025.47 vs 1656.64 visits, p?<?.0001; Stage IV: 2825.73 vs 2422.26 visits, p?<?.0001). Total direct costs per person-month in patients with pre-existing COPD were significantly higher than the non-COPD group across all services ($54,799.16 vs $41,862.91). Outpatient visits represented the largest cost category across all services in both groups, with higher costs among the COPD group ($41,203 vs $31,140.08).

Conclusion: Healthcare utilization and costs among lung cancer patients with pre-existing COPD was ～2–3-times higher than the non-COPD group.     

Major bleeding risk and healthcare economic outcomes of non-valvular atrial fibrillation patients newly-initiated with oral anticoagulant therapy in the real-world setting

Aims: This study compared the risk for major bleeding (MB) and healthcare economic outcomes of patients with non-valvular atrial fibrillation (NVAF) after initiating treatment with apixaban vs rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients who initiated apixaban, rivaroxaban, dabigatran, or warfarin were identified from the IMS Pharmetrics Plus database (January 1, 2013–September 30, 2015). Propensity score matching (PSM) was used to balance differences in patient characteristics between study cohorts: patients treated with apixaban vs rivaroxaban, apixaban vs dabigatran, and apixaban vs warfarin. Risk of hospitalization and healthcare costs (all-cause and MB-related) were compared between matched cohorts during the follow-up.

Results: During the follow-up, risks for all-cause (hazard ratio [HR]?=?1.44, 95% confidence interval [CI]?=?1.2–1.7) and MB-related (HR?=?1.57, 95% CI?=?1.0–2.4) hospitalizations were significantly greater for patients treated with rivaroxaban vs apixaban. Adjusted total all-cause healthcare costs were significantly lower for patients treated with apixaban vs rivaroxaban ($3,950 vs $4,333 per patient per month [PPPM], p?=?.002) and MB-related medical costs were not statistically significantly different ($100 vs $233 PPPM, p?=?.096). Risk for all-cause hospitalization (HR?=?1.98, 95% CI?=?1.6–2.4) was significantly greater for patients treated with dabigatran vs apixaban, although total all-cause healthcare costs were not statistically different. Risks for all-cause (HR?=?2.22, 95% CI?=?1.9–2.5) and MB-related (HR?=?2.05, 95% CI?=?1.4–3.0) hospitalizations were significantly greater for patients treated with warfarin vs apixaban. Total all-cause healthcare costs ($3,919 vs $4,177 PPPM, p?=?.025) and MB-related medical costs ($96 vs $212 PPPM, p?=?.026) were significantly lower for patients treated with apixaban vs warfarin.

Limitations: This retrospective database analysis does not establish causation.

Conclusions: In the real-world setting, compared with rivaroxaban and warfarin, apixaban is associated with reduced risk of hospitalization and lower healthcare costs. Compared with dabigatran, apixaban is associated with lower risk of hospitalizations.