Impact of chronic fibrosing interstitial lung disease on healthcare use: association between fvc decline and inpatient hospitalization.

BACKGROUND: Many types of interstitial lung diseases (ILDs) may transition to progressive chronic-fibrosing ILDs with rapid lung function decline and a negative survival prognosis. In real-world clinical settings, forced vital capacity (FVC) measures demonstrating progressive decline may be linked to negative outcomes, including increased risks of costly healthcare resource utilization (HRU). Thus, we assessed the relationship between rate of decline in lung function and an increase in HRU, specifically inpatient hospitalization, among patients with chronic fibrosing ILD. METHODS: This study utilized electronic health records from 01-Oct-2015 to 31-Oct-2019. Eligible patients (≥ 18 years old) had ≥ 2 fibrosing ILD diagnosis codes, clinical activity for ≥ 15 months, and ≥ 2 FVC tests occurring 6 months apart. Patients with missing demographic data, IPF, or use of nintedanib or pirfenidone were excluded. Two groups were defined by relative change in percent of predicted FVC (FVC% pred) from baseline to 6 months: significant decline (≥ 10%) vs. marginal decline/stable FVC (decrease < 10% or increase). The primary outcome was defined as the occurrence of an inpatient hospitalization 6 months after the first FVC value. Descriptive and multivariable analysis was conducted to examine the impact of FVC decline on occurrence of inpatient hospitalization. RESULTS: The sample included 566 patients: 13% (n = 75) with significant decline and 87% (n = 491) with marginal decline/stable FVC; their mean age (SD) was 65 (13.7) years and 56% were female. Autoimmune diagnoses were observed among 40% of patients with significant decline, and 27% with marginal decline/stable FVC. The significant decline group had better lung function at baseline than the marginal/stable group. For patients with FVC% <80% at baseline, reduction of FVC% ≥10% was associated with significantly increased odds of an inpatient hospitalization (odds ratio [OR] 2.85; confidence interval [CI] 1.17, 6.94 [p = 0.021]). CONCLUSION: Decline in FVC% ≥10% was associated with increased odds of inpatient hospitalization among patients with reduced lung function at baseline. These findings support the importance of preserving lung function among patients with fibrosing ILD.

Burden of illness in progressive fibrosing interstitial lung disease.

BACKGROUND: Progressive fibrosing interstitial lung disease (ILD) is a relatively new clinical concept describing a variety of ILDs characterized by progressive pulmonary fibrosis with associated lung function decline and worsening chest imaging. Little is known about health care resource utilization (HCRU) and costs associated with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF). This study analyzed the adjusted HCRU and cost burden among patients with incident non-IPF progressive fibrosing ILD vs matched patients with incident fibrosing ILD that had not yet progressed. METHODS: This was a retrospective study of insured US adults newly diagnosed with non-IPF fibrosing ILD from October 2016 to June 2019, conducted using administrative claims data from the Optum Research Database. Progressive disease was identified using claims-based proxies comprising health care utilization associated with management of progressive fibrosing ILD. Patients in the progressive population were 1:1 propensity score matched to not-yet-progressed patients on the basis of baseline demographic and clinical characteristics. All-cause HCRU and health care costs were presented as weighted per-patient-per-month (PPPM) measures to account for variable follow-up. Differences in study outcomes between matched cohorts were evaluated using Z-tests for continuous measures and Rao-Scott tests for binary measures. RESULTS: The postmatch cohorts comprised 11,025 patients with evidence of progression matched to 11,025 patients with not-yet-progressed fibrosing ILD. Mean (SD) weighted PPPM counts of follow-up health care encounters were significantly higher for the progressive vs not-yet-progressed cohort: ambulatory visits, 4.2 (3.6) vs 3.1 (3.3); emergency department visits, 0.3 (0.5) vs 0.1 (0.3); and inpatient (IP) stays, 0.1 (0.2) vs 0.0 (0.1) (P < 0.001 for all). Among patients with an IP stay, those with progressive disease had more inpatient days than those with not-yet-progressed disease (mean [SD] 1.6 [2.4] days vs 1.0 [1.3] days, P < 0.001). Mean weighted PPPM (SD) all-cause health care costs were also significantly higher for progressive vs not-yet-progressed patients, including total costs ($4,382 [$9,597] vs $2,243 [$4,162], P < 0.001), medical costs ($3,662 [$9,150] vs $1,627 [$3,524], P < 0.001), and pharmacy costs ($720 [$2,097] vs $616 [$2,070], P = 0.002). The difference in medical costs between cohorts was driven primarily by higher inpatient costs for progressive vs not-yet-progressed patients ($1,729 [$7,557] vs $523 [$2,118], P < 0.001). CONCLUSIONS: Progressive fibrosing ILD carries a substantial economic and health care burden. Among patients with incident non-IPF fibrosing ILD, all-cause HCRU and costs were significantly higher for those with a progressive phenotype than for matched patients whose disease had not yet progressed. The cost differential was driven primarily by hospitalizations, which were longer and more frequent for the progressive cohort. Disclosures: This work was funded by Boehringer Ingelheim Pharmaceuticals, Inc. Drs Conoscenti and Shetty are employees of Boehringer Ingelheim (BI). Dr Singer was an employee of BI at the time the study was conducted. Dr Brown was a paid consultant for BI for this study. Dr Bengtson, Ms Anderson, and Dr Brekke are employees of Optum, which was contracted by BI to conduct the study. Medical writing assistance was provided by Yvette Edmonds, PhD (Optum), and was contracted and funded by Boehringer Ingelheim Pharmaceuticals, Inc.

Impact of timing of nintedanib initiation among patients newly diagnosed with idiopathic pulmonary fibrosis.

AIMS: While nintedanib treatment has been shown to slow the progression of idiopathic pulmonary fibrosis (IPF) in patients across varying levels of lung function, the effect of treatment timing on outcomes has not been examined. We assessed hospitalization risk and medical costs among patients with IPF based on the timing of nintedanib initiation after IPF diagnosis. MATERIALS AND METHODS: This retrospective administrative claims study included data from 04/01/2014-09/30/2019 for patients aged ≥40 years who initiated nintedanib within 1 year of IPF diagnosis. Patients were assigned to study cohorts based on the time from IPF diagnosis to nintedanib initiation. All-cause hospitalization and all-cause medical costs were modeled using marginal structural models including inverse probability weights to adjust for both baseline and time-varying characteristics. RESULTS: Of 11,195 patients diagnosed with IPF during the identification period, 449 met the study selection criteria (mean age 72.3 years, 68% male, mean follow-up time 13.3 months). Adjusted hospitalization risk and medical costs both varied significantly by the timing of nintedanib initiation (p < .001 and p = .020, respectively). Adjusted weighted hospitalization risk was higher among untreated vs. treated patients in months 2-3, months 4-6, and months 7-12 after diagnosis (hazard ratio [95% CI] 1.97 [1.09-3.56], p = .026; 2.62 [1.22-5.63], p = .014; and 5.57 [2.31-13.45], p < .001, respectively). Medical costs were 69% higher for patients initiating treatment in months 2-3 vs. month 1 (cost ratio [95% CI] 1.69 [1.20-2.38], p = .003). LIMITATIONS: Disease severity could not be assessed because clinical data were unavailable; however, proxies such as oxygen use were included to adjust for between-cohort differences in disease severity. CONCLUSIONS: Patients who initiate nintedanib promptly after IPF diagnosis may have reduced hospitalization risk and medical costs compared with those who start treatment later. Additional studies are warranted to improve understanding of the impact of prompt antifibrotic therapy on patient outcomes.

Claims-based Prevalence of Disease Progression among Patients with Fibrosing Interstitial Lung Disease Other than Idiopathic Pulmonary Fibrosis in the United States.

Rationale: Chronic fibrosing interstitial lung disease (ILD) with a progressive phenotype is a clinical concept describing the broad group of ILDs characterized by progressive pulmonary fibrosis. The prevalence of progressive fibrotic ILDs other than idiopathic pulmonary fibrosis (IPF) is not well understood. Objectives: We used a novel algorithm to estimate the prevalence range of disease progression among patients with non-IPF fibrotic ILD in a U.S. claims database. Methods: This was a retrospective study including adults with commercial or Medicare Advantage with Part D (MAPD) insurance using administrative claims data from October 2015 to September 2019. Patients likely to have non-IPF fibrosing ILD with a progressive phenotype were identified via an algorithm that incorporated ILD-related diagnosis codes (excluding IPF) and claims-based proxies for fibrotic ILD progression, including pulmonary function tests, chest imaging, oral corticosteroid (OCS) medications, immunosuppressive medications, lung transplant, oxygen therapy, palliative care, and respiratory hospitalization. The prevalence range of non-IPF fibrotic ILD with progressive disease behavior was calculated using strict and lenient case definitions to account for potential imprecision in the progression proxies. Results: Of nearly 9 million study-eligible patients, 17,136 were identified with non-IPF fibrosing ILD. The prevalence of disease progression per 10,000 (95% confidence interval) ranged from 12.14 (11.74-12.54) to 29.05 (28.43-29.67) over a mean observation time of 1.44 years for MAPD enrollees (n = 14,686), and from 0.89 (0.81-0.97) to 2.36 (2.24-2.48) over a mean observation time of 1.29 years for commercial enrollees (n = 2,450). Prevalence estimates increased with age for both insurance types. Among patients with progression, 4,097 met at least two progression proxies not considering OCS (strict case definition) and 9,946 met at least one progression proxy (lenient case definition). The mean (standard deviation) number of proxies met was 2.1 (1.3), and the most common individual proxies met (alone or in combination with other proxies) were OCS use (48.9%), respiratory hospitalization (44.2%), and oxygen therapy (44.1%). Conclusions: This is among the first claims-based estimates of the prevalence of non-IPF chronic fibrosing ILD with a progressive phenotype. Our analysis indicates that this phenotype is rare in the overall population but increases substantially with increasing age.

Healthcare Costs and Resource Utilization Associated with the Use of Empagliflozin Versus Other Antihyperglycemic Agents Among Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: A Real-World Retrospective Cohort Analysis.

INTRODUCTION: Empagliflozin has demonstrated lower rates of cardiovascular outcomes vs. standard of care among patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). However, the impact of empagliflozin compared to other branded antihyperglycemic agents (AHAs) on total cost of care has yet to be quantified. METHODS AND RESULTS: This retrospective cohort study evaluated the impact of empagliflozin (n = 441) on costs and healthcare resource utilization (HCRU) vs. other branded AHAs (n = 13,122) among patients with T2DM and CVD, using the IQVIA PharMetrics® Plus Claims Database (1 August 2013-31 December 2017). Date of the first prescription (index date) for empagliflozin or other branded AHAs was used to classify patients into study cohorts. All-cause costs and HCRU were computed on a per patient per month (PPPM) basis and compared across study cohorts using outcome-appropriate statistical models. Overall, the empagliflozin cohort was younger and had a lower comorbidity burden. After covariate adjustment, the total all-cause costs (mean difference - $412 PPPM; 95% CI - $593, - $214) were significantly lower for the empagliflozin cohort. These cost differences were mainly driven by lower all-cause medical costs (mean difference - $400 PPPM; 95% CI - $577, - $196). For HCRU, the mean adjusted all-cause visits in the physician office and other outpatient settings were lower with empagliflozin vs. other branded AHAs (p < 0.001). CONCLUSIONS: This study demonstrated that the all-cause healthcare costs and HCRU were significantly lower for patients with T2DM and CVD who initiated empagliflozin vs. other branded AHAs. Along with the positive clinical evidence base of empagliflozin, these results can guide healthcare decision makers during therapy selection.

Cost-effectiveness of second-line empagliflozin versus liraglutide for type 2 diabetes in the United States.

AIM: To estimate the cost-effectiveness of sequential use of the sodium-glucose co-transporter-2 inhibitor empagliflozin and glucagon-like peptide-1 receptor agonist liraglutide after metformin in patients with type 2 diabetes (T2D) from the US payer perspective. MATERIALS AND METHODS: An economic simulation model with a lifetime horizon was developed to estimate T2D-related complications (including cardiovascular [CV] death, myocardial infarction, stroke, and renal outcomes) using EMPA-REG OUTCOME data or UK Prospective Diabetes Study risk equations, in patients with or without a history of cardiovascular disease (CVD), respectively. Evidence synthesis methods were used to provide effectiveness inputs for empagliflozin and liraglutide. Population characteristics, adverse event rates, treatment escalation, costs ($2019), and utilities (both discounted 3%/year) were taken from US sources. RESULTS: Compared with second-line liraglutide in the overall T2D population, second-line empagliflozin was dominant as it was associated with lower total lifetime cost ($11 244/patient less) and resulted in a quality-adjusted life-year (QALY) gain (0.32/patient). Second-line empagliflozin was associated with reductions in CV death (by 5%) and lower cumulative complication rates in patients with CVD (by 2%), relative to second-line liraglutide. These findings were consistent among patients with co-morbid CVD, with gains in incremental QALYs (0.43/patient) and lower lifetime cost (by $10 175/patient) relative to second-line liraglutide. Scenario analyses consistently showed dominance for second-line empagliflozin. CONCLUSION: For patients with T2D, use of second-line empagliflozin combined with metformin was a dominant strategy for US payers, associated with extended survival, improved QALYs, and lower costs compared with second-line liraglutide.

Quantifying the Risk Continuum for Cardiovascular Death in Adults with Type 2 Diabetes.

OBJECTIVES: In type 2 diabetes (T2D), the most common causes of death are cardiovascular (CV) related, accounting for >50% of deaths in some reports. As novel diabetes therapies reduce CV death risk, identifying patients with T2D at highest CV death risk allows for cost-effective prioritization of these therapies. Accordingly, the primary goal of this study was to quantify the risk continuum for CV death in a real-world T2D population as a means to identify patients with the greatest expected benefit from cardioprotective antidiabetes therapies. METHODS: This retrospective study included patients with T2D receiving services through an integrated health-care system and used data generated through electronic medical records (EMRs). Quantifying the risk continuum entailed developing a prediction model for CV death, creating an integer risk score based on the final prediction model and estimating future CV death risk according to risk score ranking. RESULTS: Among 59,180 patients with T2D followed for an average of 7.5 years, 15,691 deaths occurred, 6,033 (38%) of which were CV related. The EMR-based prediction model included age, established CV disease and risk factors and glycemic indices (c statistic = 0.819). The 10% highest-risk patients according to prediction model elements had an annual CV death risk of ∼5%; the 25% highest-risk patients had an annual risk of ∼2%. CONCLUSIONS: This study incorporated a prediction modelling approach to quantify the risk continuum for CV death in T2D. Prospective application allows us to rank individuals with T2D according to their CV death risk, and may guide prioritization of novel diabetes therapies with cardioprotective properties.

Cost-effectiveness analysis of empagliflozin versus sitagliptin as second-line therapy for treatment in patients with type 2 diabetes in the United States.

AIM: To estimate the cost-effectiveness of sequential addition of empagliflozin versus sitagliptin after metformin in patients with type 2 diabetes (T2D) with or without cardiovascular disease (CVD) from the perspective of the US healthcare payer. METHODS: An individual simulation model predicted lifetime diabetes-related complications, using UKPDS-OM2 equations in patients without CVD, and EMPA-REG OUTCOME equations in patients with CVD. Additional US-based sources informed inputs for population characteristics, adverse events, non-CV death, treatment escalation, quality of life and costs. Costs and quality-adjusted life-years (QALYs) were discounted 3.0% annually. RESULTS: The incremental cost-effectiveness ratio (ICER) for second-line empagliflozin versus sitagliptin in the overall T2D population was $6967/QALY. Empagliflozin led to longer CVD-free survival (0.07 years) and an 11% reduction in CV death in patients with CVD compared with sitagliptin. Empagliflozin resulted in greater benefits with greater costs in patients with versus without baseline CVD, yielding ICERs of $3589/QALY versus $12 577/QALY, respectively. Results were consistent across a range of deterministic and probabilistic sensitivity analyses and scenarios. CONCLUSION: Compared with sitagliptin, empagliflozin was cost-effective (at $50 000/QALY US threshold) as a second-line treatment to metformin for T2D patients with or without CVD in the United States. Our findings lend additional support for more widespread adoption of guidelines by healthcare decision-makers for T2D treatment.

A risk prediction model for heart failure hospitalization in type 2 diabetes mellitus.

BACKGROUND: Antidiabetic therapies have shown disparate effects on hospitalization for heart failure (HHF) in clinical trials. This study developed a prediction model for HHF in type 2 diabetes mellitus (T2DM) using real world data to identify patients at high risk for HHF. HYPOTHESIS: Type 2 diabetics at high risk for HHF can be identified using information generated during usual clinical care. METHODS: This electronic medical record- (EMR-) based retrospective cohort study included patients with T2DM free of HF receiving healthcare through a single, large integrated healthcare system. The primary endpoint was HHF, defined as a hospital admission with HF as the primary diagnosis. Cox regression identified the strongest predictors of HHF from 80 candidate predictors derived from EMRs. High risk patients were defined according to the 90th percentile of estimated risk. RESULTS: Among 54,452 T2DM patients followed on average 6.6 years, estimated HHF rates at 1, 3, and 5 years were 0.3%, 1.1%, and 2.0%. The final 9-variable model included: age, coronary artery disease, blood urea nitrogen, atrial fibrillation, hemoglobin A1c, blood albumin, systolic blood pressure, chronic kidney disease, and smoking history (c = 0.782). High risk patients identified by the model had a >5% probability of HHF within 5 years. CONCLUSIONS: The proposed model for HHF among T2DM demonstrated strong predictive capacity and may help guide therapeutic decisions.

The cost of cardiovascular-disease-related death in patients with type 2 diabetes mellitus.

OBJECTIVES: To assess the magnitude of difference in all-cause healthcare resource utilization (HCRU) and costs between patients with type 2 diabetes mellitus (T2DM) who died from a cardiovascular disease (CVD)-related cause in the year preceding death vs. those who did not die during this same period. METHODS: A large US administrative claims database was used to identify patients with T2DM who died of a CVD-related cause from July 2012 to April 2015. These patients were matched 1:1 to patients with T2DM who did not die, using direct matching methods. HCRU and costs were assessed in each of the four quarters (Q4: 12-10 months; Q3: 9-7 months; Q2: 6-4 months; and Q1: 3-0 months) prior to death and compared between patient cohorts using paired t-tests and McNemar's tests. RESULTS: A final matched cohort of 7648 patients who died and 7648 patients who did not die were identified. A significantly higher proportion of patients who died utilized inpatient services vs. those who did not die (Q4: 12.6% vs. 4.6%, p < .001; Q3: 14.6% vs. 4.6%, p < .001; Q2: 17.6% vs. 5.5%, p < .001; and Q1: 65.0% vs. 10.1%, p < .001). In addition, patients who died incurred significantly higher all-cause costs (Q4: $8882 vs. $3970, p < .001; Q3: $10,462 vs. $3661, p < .001; Q2: $12,564 vs. $4169, p < .001; and Q1: $36,076 vs. $6319, p < .001). CONCLUSIONS: T2DM patients with a CVD-related death had significantly greater HCRU and costs in the year including and preceding death compared to those who did not die.

Incremental burden of type 2 diabetes in patients experiencing cardiovascular hospitalizations.

OBJECTIVE: To evaluate the incremental economic burden of type 2 diabetes in patients experiencing cardiovascular (CV) hospitalizations. RESEARCH DESIGN AND METHODS: Adults with ≥1 CV hospitalization were identified using a US-based healthcare claims database from 1 July 2011 to 30 June 2014. Outcomes for patients surviving the index hospitalization were compared between patients with vs. without type 2 diabetes (cohorts were identified in the pre-index period). Subsequent CV hospitalizations were evaluated using Cox proportional hazards models. All-cause and CV-related healthcare resource utilization (HCRU) and costs captured on a per-patient per-month (PPPM) basis during a variable follow-up period were evaluated using appropriate multivariable regression models. RESULTS: Of 316,207 patients with ≥1 CV hospitalization, 23% had comorbid type 2 diabetes. The mean age ± SD was 62.6 ± 12.3 years and 64.4% were male. During follow-up, the type 2 diabetes cohort had a 19% higher risk of subsequent CV hospitalizations compared to the non-type-2-diabetes cohort (p < .001). This difference in risk was highest in patients aged 35-44 years. Subsequent all-cause hospitalizations for the type 2 diabetes cohort were longer (mean length of stay, 6.7 vs. 6.3 days; p < .001), with higher total bed-days PPPM (mean, 0.52 vs. 0.43; p < .001), compared to the non-type-2-diabetes cohort. The type 2 diabetes cohort had a significantly higher incremental cost for both the index CV hospitalization (mean cost difference, $1046; p < .001) and all-cause costs PPPM following discharge (mean cost difference, $749; p < .001). CONCLUSIONS: Comorbid type 2 diabetes was associated with an increased risk of subsequent CV hospitalizations and higher costs and HCRU during the follow-up period.

Concordance with prescribing information dosage recommendations for dipeptidyl-peptidase-4 inhibitors among type 2 diabetes mellitus patients with moderate to severe chronic kidney disease.

OBJECTIVE: To estimate the proportion of patients with moderate to severe chronic kidney disease (CKD) whose initial dipeptidyl-peptidase-4 inhibitor (DPP4-i) dosage was concordant with prescribing information (label) recommendations in the United States. METHODS: Adult patients with type 2 diabetes mellitus (T2DM) who initiated a DPP4-i (linagliptin, sitagliptin, saxagliptin) between 1 January 2011 and 30 June 2014 were identified using electronic medical records and administrative claims, with index date being the date of first observed DPP4-i treatment. Patients were required to have chronic kidney disease (CKD) stage 3b, 4 or 5 (estimated Glomerular Filtration Rate [eGFR] value <45 ml/min/1.73 m2) during the 12 month pre-index period. Patients were classified as concordant or not concordant based on whether the first prescribed dose was consistent with label recommendations. Demographics, clinical characteristics, resource use and costs during pre-index were evaluated by DPP4-i concordance status. RESULTS: Of the 492 patients (323 sitagliptin, 57 saxagliptin, 112 linagliptin), 36.2% were prescribed doses that were not concordant with label recommendations (44.9% for sitagliptin, 57.9% for saxagliptin and 0% for linagliptin [which does not require dosage adjustment]). Concordant patients were slightly older (mean age 71 years vs. 68, p = .01) but had similar gender distribution (55% vs. 60% female, p = .31) compared to those who were not concordant. They had lower general health status (Charlson Comorbidity Score 2.6 vs. 2.2, p = .03), and had similar pre-index all-cause total costs ($25,245 vs. $21,972, p = .68) and lower pre-index T2DM-related costs ($1618 vs. $1922, p = .05). CONCLUSIONS: More than a third of DPP4-i patients with CKD stage 3b or higher were prescribed doses not concordant with DPP4-i label dosage recommendations.

Hypoglycemia Incidence Rates and Associated Health Care Costs in Patients with Type 2 Diabetes Mellitus Treated with Second-Line Linagliptin or Sulfonylurea After Metformin Monotherapy.

BACKGROUND: Hypoglycemia poses a significant clinical and economic burden to patients with type 2 diabetes mellitus (T2DM). Minimizing the risk of hypoglycemia is an important component when managing patients with T2DM. Understanding hypoglycemia rates and the associated economic consequences can help to inform health care decision makers. OBJECTIVE: To assess hypoglycemia incidence rates and associated costs in patients who initiated second-line treatment with the antidiabetic agents linagliptin or a sulfonylurea (SU) after metformin. METHODS: A large U.S. administrative claims database was used to identify patients with T2DM (during the identification period July 2011-October 2013) who initiated linagliptin or a SU after metformin use. The date of the first prescription for linagliptin or a SU during the identification period was designated as the index date. Linagliptin users were matched to SU users based on demographic and clinical characteristics identified within a 12-month period before the index date using propensity scores (1:3 ratio, caliper: ±0.001). Rates and costs (2013 U.S. dollars) of hypoglycemia resulting in any health care resource use were quantified during a variable follow-up period (i.e., end of the study, end of the 12-month follow-up, treatment regimen change, or disenrollment, whichever came first). Hypoglycemia rates per 100 person-years were compared using univariate Poisson regression, and hazard of hypoglycemia was obtained from multivariate Cox proportional hazards regression. Mean monthly hypoglycemia-related costs, all-cause costs, and T2DM-related costs were computed for patients with hypoglycemia and compared using t-tests. RESULTS: Propensity-score matching resulted in a sample of 11,536 patients (linagliptin = 2,884; SU = 8,652) with a mean age of 56 years and 59% male. The rate of hypoglycemia (per 100 person-years) was lower in the linagliptin than the SU user groups (2.51 vs. 3.63; P= 0.049). Linagliptin users had a 33% lower risk of hypoglycemia compared with SU users (HR = 0.67; 95% CI = 0.47-0.97; P= 0.031). Among patients who had hypoglycemia, linagliptin users showed numerically lower mean monthly hypoglycemia-related costs compared with SU users ($300 vs. $890; P= 0.092), which was primarily driven by differences in hypoglycemia-related costs in the hospital setting. A similar theme was observed with monthly all-cause costs (linagliptin users, $1,971 vs. SU users, $3,758; P= 0.092). CONCLUSIONS: Linagliptin use was associated with a lower incidence rate of hypoglycemia compared with SU use in patients initiating second-line therapy after metformin monotherapy. Among patients who experienced hypoglycemia, linagliptin users appeared to have lower monthly hypoglycemia-related and all-cause costs than SU users. Careful consideration of newer treatment alternatives may be prudent for optimal T2DM management, especially with regard to hypoglycemia. DISCLOSURES: Funding for the research study and resultant publication was provided by Boehringer Ingelheim. Shetty is an employee of Boehringer Ingelheim. Cai was an employee of Boehringer Ingelheim at the time of the study. Raju and D'Souza are employees of Xcenda, which received research funding from Boehringer Ingelheim for the conduct of this study and for the preparation of this manuscript. All authors contributed to concept and study design. Raju took the lead in data analysis, along with D'Souza, and all authors contributed equally to data interpretation. The manuscript was written by Raju, D'Souza, Cai, and Shetty and revised primarily by Raju, along with Shetty and D'Souza.

A comparison of mortality and costs associated with FOLFOX versus FOLFIRI in stage IV colorectal cancer.

OBJECTIVE: To examine cost and mortality among stage IV colorectal cancer (CRC) patients treated with 5-fluorouracil (5FU)/leucovorin/oxaliplatin (FOLFOX) or 5FU/leucovorin/irinotecan (FOLFIRI). METHODS: Adult CRC patients newly treated with FOLFOX or FOLFIRI were identified from a large database using medical and pharmacy claims for services delivered January 1, 2002 through December 31, 2005. Cancer stage for a subset of patients was abstracted from medical records. Outcomes were annualized costs calculated for 4 years of observation, and deaths as recorded by the National Death Index. Cost was analyzed using generalized linear modeling; mortality was modeled using Cox proportional hazards analysis. RESULTS: Unadjusted annualized median and mean costs were $134,401 and $152,213, respectively, for the FOLFOX cohort (n = 41) and $103,150 and $107,994 for the FOLFIRI cohort (n = 86). Death occurred among five (12%) FOLFOX and 42 (53%) FOLFIRI patients. Adjusted analysis revealed no significant difference in cost between cohorts, even after adjusting for reduced irinotecan costs due to generic availability. Incremental costs associated with one additional life saved per year were only $1,236 higher for patients treated with FOLFOX compared with FOLFIRI. Cox analysis revealed a significant survival advantage for FOLFOX over FOLFIRI (HR = 5.2; 95% CI: 1.7-15.8). CONCLUSIONS: A significant survival benefit was seen for CRC patients receiving FOLFOX versus FOLFIRI; multivariate analysis revealed no significant cost differences. However, the small sample size may have resulted in lack of adequate power to detect a difference between cohorts. There may be factors influencing mortality that were not included in the multivariate modeling.