Economic burden related to fistulas or strictures among commercially insured patients with Crohn's disease in the United States.

BACKGROUND: Crohn's disease (CD) is a chronic, progressive, immune-mediated gastrointestinal condition that can lead to fistulizing or stricturing complications. OBJECTIVE: To quantify the burden of illness related to fistulas and/or strictures in patients with CD. METHODS: Using the Optum Research Database from October 2015 to December 2019, patients with CD were classified according to 1 of 3 condition cohorts: CD with fistula (CD-F), CD with stricture (CD-S), or CD with fistula and stricture (CD-FS). Each cohort was matched to a nonfistula, nonstricture CD cohort. Postdiagnosis per patient per year (PPPY) costs and health care resource utilization were assessed, accounting for variable lengths of follow-up periods. Multivariable generalized linear models were used to estimate the adjusted mean costs in each cohort. RESULTS: The CD-F, CD-S, and CD-FS cohorts included 1,317; 4,650; and 894 patients, respectively. The mean age of patients within the CD-S and their comparator cohorts was higher than in the CD-F or CD-FS cohorts (59.9 vs 49.5 vs 49.6 years). At baseline, cardiovascular disease was the most common comorbidity across all condition and comparator cohorts. Condition cohorts had 2-4 times more inpatient visits, 5-8 times more surgical visits, and 2-3 times more endoscopies PPPY than comparator cohorts. Compared with their respective comparator cohort, patients in the 3 condition cohorts had higher medication, medical, and total health care costs. CONCLUSIONS: This study demonstrates a significant economic burden related to fistulas and/or strictures among patients with CD, highlighting the importance of prevention, early recognition, and appropriate management of CD-related complications. DISCLOSURES: Yanni Fan, Ling Zhang, Jennifer S Thompson, and Kimberly G Brodovicz are employees of Boehringer Ingelheim. Rhonda L Bohn, Monik C Jiménez, and Stephani Gray (Bohn Epidemiology, LLC) are paid consultants to Boehringer Ingelheim. Gil Y Melmed reports receiving grants from Pfizer; consulting fees from Boehringer Ingelheim, AbbVie, Arena, BMS, Celgene, Entasis, Ferring Lilly, Fresenius Kabi, Medtronic, Samsung Bioepis, Janssen, Takeda, Pfizer, Prometheus Labs, and TechLab. We conducted a retrospective study using administrative claims data from the Optum Research Database, a database of a commercially insured population in the United States. All patient data were anonymized and deidentified; therefore, informed consent was not necessary. Restrictions apply to the availability of these data because of a contract between Optum and Boehringer Ingelheim, and data are thus unavailable to the public. For enquiries on the dataset analyzed in this study, please contact Optum (https://www.optum.com).

Effectiveness and safety of empagliflozin in routine care patients: Results from the EMPagliflozin compaRative effectIveness and SafEty (EMPRISE) study.

AIM: To investigate effectiveness and safety outcomes among patients with type 2 diabetes (T2D) initiating empagliflozin versus dipeptidyl peptidase-4 (DPP-4) inhibitor treatment across the broad spectrum of cardiovascular risk. METHODS: In a population-based cohort study we identified 39 072 pairs of 1:1 propensity score-matched adult patients with T2D initiating empagliflozin or DPP-4 inhibitors, using data from 2 US commercial insurance databases and Medicare between August 2014 and September 2017. The primary outcomes were a composite of myocardial infarction (MI)/stroke, and hospitalization for heart failure (HHF). Safety outcomes were bone fractures, lower-limb amputations (LLAs), diabetic ketoacidosis (DKA), and acute kidney injury (AKI). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for more than 140 baseline covariates. RESULTS: Study participants had a mean age of 60 years and only 28% had established cardiovascular disease. Compared to DPP-4 inhibitors, empagliflozin was associated with similar risk of MI/stroke (HR 0.99 [95% CI 0.81-1.21]), and lower risk of HHF (HR 0.48 [95% CI 0.35-0.67] and 0.63 [95% CI 0.54-0.74], based on a primary and any heart failure discharge diagnosis, respectively). The HR was 0.52 (95% CI 0.38-0.72) for all-cause mortality (ACM) and 0.83 (95% CI 0.70-0.98) for a composite of MI/stroke/ACM. Empagliflozin was associated with a similar risk of LLA and fractures, an increased risk of DKA (HR 1.71 [95% CI 1.08-2.71]) and a decreased risk of AKI (HR 0.60 [95% CI 0.43-0.85]). CONCLUSIONS: In clinical practice, the initiation of empagliflozin versus a DPP-4 inhibitor was associated with a lower risk of HHF, ACM and MI/stroke/ACM, a similar risk of MI/stroke, and a safety profile consistent with documented information.

Health Care Costs by Type of Expenditure across eGFR Stages among Patients with and without Diabetes, Cardiovascular Disease, and Heart Failure.

BACKGROUND: CKD is associated with higher health care costs that increase with disease progression. However, research is lacking on the type of health care costs associated with CKD across all stages in a general population with a substantial comorbidity burden. METHODS: Using electronic medical records of an integrated delivery system, we evaluated health care costs by expenditure type in general and in patients with CKD by eGFR and presence of comorbidities. We categorized 146,132 patients with eGFR data in 2016 or 2017 and examined nonmutually exclusive groups according to presence of diabetes mellitus, cardiovascular disease, or heart failure. We used 1 year of follow-up data to calculate outpatient, inpatient, emergency, pharmaceutical, dialysis, and total health care costs by eGFR (Kidney Disease Improving Global Outcomes-defined eGFR categories), adjusted for age, sex, and nonwhite race. RESULTS: Mean total health care costs among patients with CKD without comorbidities were 31% higher than among patients without CKD ($7374 versus $5631, respectively). Hospitalizations accounted for 35% of total costs among those with CKD and no comorbidities but up to 55% among patients with CKD and heart failure. The proportion of costs attributable to hospitalizations accelerated with declining kidney function, reaching as high as 66%. CONCLUSIONS: Poorer kidney function and the presence of diabetes mellitus, cardiovascular disease, or heart failure drive substantial health care costs and increase the proportion of costs attributable to inpatient care. The large contribution of inpatient costs begins in earlier stages of CKD and escalates as kidney function declines. Additional therapies to reduce CKD incidence, slow CKD progression, and lower hospitalization risk are needed to benefit patients and reduce CKD's economic burden.

Preferential prescribing of linagliptin in type 2 diabetes patients in an expanded post-marketing surveillance study in Japan.

AIMS/INTRODUCTION: To evaluate linagliptin prescribing in type 2 diabetes mellitus patients with different comorbidities, an expanded Japanese post-marketing surveillance also collected baseline data for patients initiating other glucose-lowering drugs. MATERIALS AND METHODS: Patients initiating linagliptin monotherapy were enrolled, then the next patient starting monotherapy with another glucose-lowering drug was enrolled (2012-2014). Baseline data were collected and analyzed by the Medical Dictionary for Regulatory Activities system organ class. Analyses were descriptive, and meaningful differences defined as absolute standardized difference >10%. RESULTS: Over 4,200 type 2 diabetes mellitus patients were enrolled. Most system-organ class comorbidities were more common in patients initiating linagliptin versus other glucose-lowering drugs, with meaningful differences observed for metabolism/nutritional (50.5 vs 45.5%, respectively), cardiac (12.2 vs 8.6%, respectively), vascular (56.4 vs 51.3%, respectively) and renal/urinary disorders (9.9 vs 5.7%, respectively). CONCLUSIONS: Expanding the linagliptin Japanese post-marketing surveillance revealed linagliptin prescribing to a type 2 diabetes mellitus population with more comorbidities versus other glucose-lowering drugs. Although such preferential prescribing might be expected, as linagliptin requires no dose adjustment or monitoring in renally or hepatically impaired patients, this innovative post-marketing surveillance approach generated important evidence that could only be shown in such a non-randomized comparative study. These data generated insights important for the design and interpretation of observational studies and spontaneous reports, which are key for public health.

Prevalence and incidence of urinary tract and genital infections among patients with and without type 2 diabetes.

OBJECTIVE: Epidemiological data on genitourinary infections (GUIs) comparing patients with and without type 2 diabetes (T2DM) is scant. We aimed to estimate the incidence of urinary tract infections (UTIs), genital infections (GIs), or any GUI in total and stratified by history of GUI and sex. RESEARCH DESIGN AND METHODS: We identified 39,295 patients in the Kaiser Permanente Northwest health plan with T2DM and an equal number of age and sex matched patients without diabetes. The cohort was followed for up to 9years (2006-2014). We calculated incidence rates and corresponding 95% confidence intervals (CI) of any GUI, UTIs and GIs adjusting for age, sex, race, BMI, presence of chronic kidney disease, annual number of outpatient visits, and diuretic use. RESULTS: Adjusted incidence of any GUI was 97.2/1000person-years (p-y) (95% CI 95.5-98.8) among the T2DM cohort vs. 79.7/1000 p-y (78.3-81.2) among those without diabetes. T2DM was associated with an adjusted 25% increased risk of UTI (rate ratio 1.25, 95% CI 1.22-1.29), a 26% increased risk of GI (1.26, 1.22-1.31) and a 22% increased risk of any GUI (1.22, 1.19-1.25). Incidence rates were lower among those with no GUI history, but the relative risks were similar. Women in both groups had higher incidence rates of GUIs than men. CONCLUSIONS: T2DM was associated with increased risks of any GUI, UTIs and GIs. Incidence rates of UTIs were higher than rates of GIs, but the relative risk of GIs was essentially identical. A similar pattern was observed when stratifying by sex. SIGNIFICANCE OF THE STUDY: RESEARCH QUESTIONS.

Review of patient-reported outcome instruments measuring health-related quality of life and satisfaction in patients with type 2 diabetes treated with oral therapy.

OBJECTIVE: Treatments and their mode of administration may represent a burden for patients and can therefore impact their health-related quality of life (HRQL) or treatment/health satisfaction. Patients with type 2 diabetes mellitus (T2DM) can be treated with oral hypoglycemic agents (OHAs), injectable medications (such as insulin), or a combination of agents. This review aimed to identify patient-reported outcome (PRO) instruments measuring HRQL and/or satisfaction that could differentiate between oral medications based on medication related attributes such as efficacy, tolerability, weight loss, dosing frequency and pill burden. RESEARCH DESIGN AND METHODS: Medline, Embase, PsycINFO, Cochrane Library and the Patient-Reported Outcome and Quality of Life Questionnaires (PROQOLID) biomedical databases were searched to identify instruments and document their development methodology, content and psychometric properties (i.e. validity, reliability), responsiveness and ability to detect changes between treatments. RESULTS: Nineteen instruments were retained based on their potential to differentiate between OHAs. Ten instruments assessed HRQL, amongst which the Audit of Diabetes Dependent Quality of Life, Diabetes 39, Diabetes Health Profile and Impact of Weight on Quality of Life displayed good psychometric properties in T2DM populations and comprehensive HRQL content. Nine instruments assessed satisfaction. Both the Oral Hypoglycemic Agent Questionnaire (OHAQ) and Diabetes Medication Satisfaction (DiabMedSat) Questionnaire have highly relevant content regarding drug attributes. The OHAQ is specific to oral treatment and the DiabMedSat includes HRQL items. The Diabetes Treatment Satisfaction Questionnaire is a standard instrument that is extensively used and provides conclusive results in studies of patients with T2DM. CONCLUSIONS: Very few of the existing PRO instruments are specific to OHAs. Despite satisfaction instruments being recommended to differentiate between OHAs in studies of T2DM based on medication attributes, we find that none of the existing instruments appear to be useful in detecting differences between treatments, therefore limiting their use in clinical and observational research.

Disease burden of urinary tract infections among type 2 diabetes mellitus patients in the U.S.

AIMS: Type 2 diabetes is a reported risk factor for more frequent and severe urinary tract infections (UTI). We sought to quantify the annual healthcare cost burden of UTI in type 2 diabetic patients. METHODS: Adult patients diagnosed with type 2 diabetes were identified in MarketScan administrative claims data. UTI occurrence and costs were assessed during a 1-year period. We examined UTI-related visit and antibiotic costs among patients diagnosed with UTI, comparing those with versus without a history of UTI in the previous year (prevalent vs. incident UTI cases). We estimated the total incremental cost of UTI by comparing all-cause healthcare costs in patients with versus without UTI, using propensity score-matched samples. RESULTS: Within the year, 8.2% (6,014/73,151) of subjects had ≥1 UTI, of whom 33.8% had a history of UTI. UTI-related costs among prevalent versus incident cases were, respectively, $603 versus $447 (p=0.033) for outpatient services, $1,607 versus $1,819 (p=NS) for hospitalizations, and $61 versus $35 (p<0.0001) for antibiotics. UTI was associated with a total all-cause incremental cost of $7,045 (95% CI: 4,130, 13,051) per patient with UTI per year. CONCLUSIONS: UTI is common and may impose a substantial direct medical cost burden among patients with type 2 diabetes.

Evidence-to-policy gap on hepatitis A vaccine adoption in 6 countries: Literature vs. policymakers' beliefs.

BACKGROUND: National vaccine adoption decisions may be better understood by linking multiple data sources. When examining countries' decisions to adopt the hepatitis A vaccine, applying multiple research methods can facilitate assessments of gaps between evidence and policy. We conducted a literature review on hepatitis A and stakeholder interviews about decisions to adopt the vaccine in six countries (Chile, India, South Korea, Mexico, Russia, and Taiwan). METHODS: A systematic literature review was conducted across five literature databases. The review identified and abstracted 340 articles, supplemented by internet search. In addition, we interviewed 62 experts and opinion leaders on hepatitis A and/or vaccines. Data from the two sources were analyzed to identify gaps around epidemiologic data, economic data, and barriers/facilitators of hepatitis A vaccine adoption. RESULTS: Epidemiologic data gaps were found in Chile and Russia, where stakeholders believed data to be more solid than the literature documented. Economic data on hepatitis A was found to be weak across all countries despite stakeholders' agreement on its importance. Barriers and facilitators of vaccine adoption such as political will, prioritization among vaccines, and global or local recommendations were discussed more by stakeholders than the literature. Stakeholders in India and Mexico were not concerned with the lack of data, despite growing recognition in the literature of the epidemiological transition and threat of outbreaks. CONCLUSIONS: Triangulation of results from two methods captured a richer story behind vaccine adoption decisions for hepatitis A. The discrepancy between policymakers' beliefs and existing data suggest a decline in priority of hepatitis A or weak investment in data collection. Filling the confirmed data gaps in seroprevalence or economic data is important to help guide policy decisions. Greater communication of the risk of hepatitis A and the benefits of the vaccine may help countries undergoing the epidemiologic transition.

Assessing the impact of propensity score estimation and implementation on covariate balance and confounding control within and across important subgroups in comparative effectiveness research.

PURPOSE: Researchers are often interested in estimating treatment effects in subgroups controlling for confounding based on a propensity score (PS) estimated in the overall study population. OBJECTIVE: To evaluate covariate balance and confounding control in sulfonylurea versus metformin initiators within subgroups defined by cardiovascular disease (CVD) history comparing an overall PS with subgroup-specific PSs implemented by 1:1 matching and stratification. METHODS: We analyzed younger patients from a US insurance claims database and older patients from 2 Medicare (Humana Medicare Advantage, fee-for-service Medicare Parts A, B, and D) datasets. Confounders and risk factors for acute myocardial infarction were included in an overall PS and subgroup PSs with and without CVD. Covariate balance was assessed using the average standardized absolute mean difference (ASAMD). RESULTS: Compared with crude estimates, ASAMD across covariates was improved 70%-94% for stratification for Medicare cohorts and 44%-99% for the younger cohort, with minimal differences between overall and subgroup-specific PSs. With matching, 75%-99% balance improvement was achieved regardless of cohort and PS, but with smaller sample size. Hazard ratios within each CVD subgroup differed minimally among PS and cohorts. CONCLUSIONS: Both overall PSs and CVD subgroup-specific PSs achieved good balance on measured covariates when assessing the relative association of diabetes monotherapy with nonfatal myocardial infarction. PS matching generally led to better balance than stratification, but with smaller sample size. Our study is limited insofar as crude differences were minimal, suggesting that the new user, active comparator design identified patients with some equipoise between treatments.