Sangaralingham, Lindsey R.

Background: High-quality diabetes care is evidence-based, timely, and equitable. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the most recently approved class of glucose-lowering medications with additional cardio- and renal-protective benefits and low risk of hypoglycemia. Cardiovascular and kidney disease are among the most common chronic diabetes complications, whereas hypoglycemia is the most prevalent adverse effect of glucose-lowering therapy. We examine the sociodemographic and clinical factors associated with early SGLT2i initiation and appropriateness of use based on contemporaneous scientific evidence. Materials and Methods: Retrospective analysis of medical and pharmacy claims data from OptumLabs ® Data Warehouse for commercially insured and Medicare Advantage adult beneficiaries with diabetes types 1 and 2, who filled any glucose-lowering medication between January 1, 2013 and December 31, 2016. Demographic (age, sex, race, income), clinical (comorbidities), and insurance-related factors affecting first prescription for a SGLT2i were examined using multivariable logistic regression. Results: Among 1,054,727 adults with pharmacologically treated diabetes, 7.2% ( n = 75,500) initiated a SGLT2i. Patients with prior myocardial infarction (MI) (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91–0.96), heart failure (HF) (OR: 0.93, 95% CI: 0.91–0.94), kidney disease (OR: 0.80, 95% CI: 0.78–0.81), and severe hypoglycemia (OR: 0.96, 95% CI: 0.94–0.98) were all less likely to start a SGLT2i; P < 0.001 for all. SGLT2i were also less likely to be started by patients ≥75 years (OR: 0.57, 95% CI: 0.55–0.59, vs. 18–44 years), Black patients (OR: 0.93, 95% CI: 0.91–0.95, vs. White), and those with Medicare Advantage insurance (OR: 0.63, 95% CI: 0.62–0.64, vs. commercial). Conclusions: Younger, healthier, non-Black patients with commercial health insurance were most likely to start taking SGLT2i. Patients with MI, HF, kidney disease, and prior hypoglycemia were less likely to use SGLT2i, despite evidence supporting their preferential use in these patients. Efforts to address this treatment-risk paradox may help improve health outcomes among patients with type 2 diabetes.

Abstract Background: Direct acting antiviral medications (DAA) have become the mainstay for treatment of chronic hepatitis C virus (HCV) infection. However, some studies have suggested an increased risk of HCC development following use of DAAs for HCV compared with use of interferon-based medications (IFN), while other studies, mostly in Veterans Administration population in the United States, did not show an increase in HCC risk after the use of DAA in patients with HCV. To address these conflicting reports, we investigated the association between use of DAA for HCV and subsequent development of HCC in a large, longitudinal data with broad representation of individuals from various ages, ethnicities, and geographic regions across the United States. Methods: A retrospective cohort study was performed using medical and pharmacy claims from the OptumLabs® Data Warehouse. The study included 9,532 incident HCV cases (2010-2016) of ages 18 years or older treated with DAA or IFN and did not have a prior diagnosis of HCC before initiation of the antiviral therapy. The participants were categorized into DAA-only or IFN-only groups. To account for confounding by indication, inverse probability of treatment weighting (IPTW) was performed to ensure balance in sociodemographic and treatment related factors between treatment groups. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HCC risk, comparing DAA-only regimen with IFN-only regimen (reference). Results: Median follow-up for the entire study cohort was 1.4 years, with a slightly longer follow-up for individuals in the IFN-only group (1.8 years) than for those in the DAA-only group (1.4 years). One hundred and seventy-one incident HCC cases developed during follow-up, with a higher occurrence of HCC in the DAA-only group (n=155; 11.9 cases per 1,000 person-years) than in the IFN-only group (n=16; 8.3 cases per 1,000 person-years). Compared with IFN-only treatment, use of DAA-only for HCV was not associated with an increase in HCC risk (HR=1.47, 95% CI: 0.89-2.42). Similarly, no association was found between use of DAA-only regimen and HCC risk among individuals with cirrhosis (HR=1.28, 95% CI: 0.71-2.31) or those without cirrhosis (HR =1.80, 95% CI: 0.64-5.03). When stratified by sustained virologic response (SVR), a measure of complete viral clearance, we noted a higher HCC risk associated with DAA-only regimen among individuals with SVR (HR=7.83, 95% CI: 1.54-39.88) and a lower risk for DAA-only regimen among those without SVR (HR=0.12, 95% CI: 0.02-0.95); however, the CIs are substantially wide, reflecting the small numbers in these subgroup analyses. Conclusion: Despite some prior reports of increased risk of HCC development following use of DAA for HCV, this ethnically and geographically diverse study did not find compelling evidence indicating an increased HCC risk associated with use of DAA in patients with HCV when compared with use of IFN. Citation Format: Samuel O. Antwi, Holly K. Van Houten, Lindsey R. Sangaralingham, Tushar Patel. Risk of de novo hepatocellular carcinoma development following use of direct acting antiviral medications for treatment of chronic hepatitis C virus infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-150.

Objective The aim of this study was to evaluate national patterns of care for women with overactive bladder (OAB) in an administrative data set and identify potential areas for improvement. Methods We performed an analysis using the OptumLabs Data Warehouse, which contains deidentified administrative claims data from a large national US health insurance plan. The study included women, older than 18 years, with a new OAB diagnosis from January 1, 2007, to June 30, 2017. We excluded those with an underlying neurologic etiology, with interstitial cystitis/painful bladder syndrome, were pregnant, or did not have continuous enrollment for 12 months before and after OAB diagnosis. Trends in management were assessed via the Cochran-Armitage test. Time to discontinuation among medications was compared using t test. Results Of 1.4 million women in the database during the study time frame, 60,246 (4%) were included in the study. Median age was 61 years [interquartile range (IQR), 50–73], and median follow-up was 2.6 years (IQR, 1.6–4.2). Overall, 37% were treated with anticholinergics, 5% with beta-3 agonists, 7% with topical estrogen, and 2% with pelvic floor physical therapy; 26% saw a specialist; and 2% underwent third-line therapy. Median time to cessation of prescription filling was longer for beta-3 agonists versus anticholinergics [median, 4.1 months (IQR, 1–15) vs 3.6 months (IQR, 1–10); P < 0.0001]. Use of third-line therapies significantly increased over the study time frame, from 1.1% to 2.2% ( P < 0.0001). Conclusions Most of the patients do not continue filling prescriptions for OAB medications, and a minority of patients were referred for specialty evaluation. Although third-line therapy use is increasing, it is used in a small proportion of women with OAB. Given these patterns, there may be underutilization of specialist referral and other OAB therapies.

Abstract Rationale Since their approval, there has been no real-world or randomized trial evidence evaluating the effect of the antifibrotic medications pirfenidone and nintedanib on clinically important outcomes such as mortality and hospitalizations. Objectives To evaluate the clinical effectiveness of the antifibrotic medications pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis. Methods Using a large U.S. insurance database, we identified 8,098 patients with idiopathic pulmonary fibrosis between October 1, 2014 and March 1, 2018. A one-to-one propensity score–matched cohort was created to compare patients treated with antifibrotic medications (n = 1,255) with those not on treatment (n = 1,255). The primary outcome was all-cause mortality. The secondary outcome was acute hospitalizations. Subgroup analyses were performed to evaluate mortality differences by drug. Measurements and Main Results The use of antifibrotic medications was associated with a decreased risk of all-cause mortality (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62–0.98; P value = 0.034). However, this association was present only through the first 2 years of treatment. There was also a decrease in acute hospitalizations in the treated cohort (HR, 0.70; 95% CI, 0.61–0.80; P value &lt;0.001). There was no significant difference in all-cause mortality between patients receiving pirfenidone and those on nintedanib (HR, 1.14; 95% CI, 0.79–1.65; P = 0.471). Conclusions Among patients with idiopathic pulmonary fibrosis, antifibrotic agents may be associated with a lower risk of all-cause mortality and hospitalization compared with no treatment. Future research should test the hypothesis that these treatments reduce early, but not long-term, mortality as demonstrated in our study.

184 Background: Population level data regarding incidence of immune-related adverse events (irAE) is lacking. This study evaluated the frequency of irAEs among a large population of patients with non-small cell lung cancer (NSCLC) who received immune checkpoint inhibitors. Methods: Administrative claims data from a large U.S. commercial insurance database (OptumLabs Data Warehouse) were used to retrospectively identify patients with NSCLC who received PD-1 or PD-L1 inhibitors between January 1, 2015 to December 31, 2017. The frequencies of irAEs were reported, identified by having a new medical claim with a corresponding ICD-9 or ICD-10 code during the time period in which the patient was on immunotherapy. Results: Of 2,798 patients with NSCLC (median age at PD-(L)1 initiation: 69 years, interquartile range: 60-75, 1558 male [55.7%], 1240 [44.3%] female), 1,998 (71.4%) received nivolumab, 699 (25.0%) received pembrolizumab, and 101 (3.6%) received atezolizumab. Most patients (1463, 52.3%) received a PD-(L)1 inhibitor as second line therapy; the majority of patients (744) received alkylating agents and antimetabolites prior to receiving PD-(L)1 therapy. See Table 1 for frequencies of irAEs. Conclusions: The current study suggests that the frequencies of some irAEs related to immune checkpoint inhibitor therapies may be higher than those which were reported in the initial trials that led to the FDA approvals for immunotherapies. For example, hypophysitis was noted to occur in 0.6% of patients in the KEYNOTE-024 trial, but was identified in 2.4% of patients in this large cohort. Real world data may refine provider and patient expectations for outcomes beyond what is observed in clinical trials. [Table: see text]