Boehringer Ingelheim Pharmaceuticals Research Articles

543. Sex Differences in Clinical Presentation and Outcomes of Adults Hospitalized with COVID-19 Pneumonia After Administration of Infliximab, Abatacept or Cenicriviroc: Subgroup Analysis from the ACTIV-1 Master Protocol

Abstract Background A growing body of evidence suggests potential sex differences in the clinical outcomes of COVID-19. In this study we evaluated whether sex and baseline clinical variables were associated with treatment effect after receipt of immunomodulators vs placebo in a study population derived from ACTIV-1 IM clinical trial. Methods ACTIV-1 IM is a master protocol that evaluated infliximab, abatacept and cenicriviroc in addition to standard of care in adult patients hospitalized with moderate or severe SARS-CoV-2 infection through randomized, double-blind comparisons to shared placebo. We performed a subgroup analysis of the modified intention-to-treat cohort. Primary outcome was association of sex with time-to-recovery at day 28, key secondary outcomes were 28-day mortality and clinical status at day 14. Results A total of 1381 participants were included. There was no difference in treatment effect for primary endpoint of time-to-recovery based on sex for infliximab (RRR 1.14, 95% CI 0.95-1.37 for males and RRR 1.09, 95% CI 0.90-1.34 for females with interaction p=0.77), abatacept (RRR 1.14, 95% CI 0.95–1.37 for males and RRR 1.13, 95% CI 0.91-1.40 for females with interaction p=0.93) or cenicriviroc (RRR 0.99, 95% CI 0.79–1.24 for males, RRR 0.98, 95% CI 0.77-1.24 for females, interaction p=0.93) substudies. There was no difference in treatment effect by sex for secondary outcomes for infliximab and abatacept substudies. The cenicriviroc substudy was terminated early for futility and found no difference in treatment effects based on sex for secondary outcomes either. Conclusion There was no difference in treatment effect for infliximab, abatacept or cenicriviroc among males vs females. This suggests a more complex interplay of pathogen and host factors deserving further research to identify therapeutic targets for COVID-19. Disclosures Radica Alicic, MD, MSc, Boehringer Ingelheim Pharmaceuticals, Inc.: Advisor/Consultant Caryn Morse, MD, Gilead Sciences Inc.: Grant/Research Support|Janssen: Grant/Research Support|Laurent Pharma: Grant/Research Support|Moderna: Grant/Research Support|Ridgeback Bio: Grant/Research Support William G. Powderly, MD, Merck: Advisor/Consultant

Real-world primary nonadherence to antiobesity medications.

BACKGROUND: Primary nonadherence (PNA), when a medication is newly prescribed but not filled, has been identified as a major research gap potentially impacting the optimal treatment of patients with overweight and obesity who are newly prescribed antiobesity medications (AOMs). OBJECTIVES: To assess PNA among patients with newly prescribed AOMs and to examine factors associated with PNA to AOMs. METHODS: This was a retrospective study that used the Optum Integrated Clinical plus Claims database to identify individuals who had at least 1 prescription order for an AOM the US Food and Drug Administration approved for long-term use. Individuals with prescription orders between January 1, 2012, and February 28, 2019, were identified, and patient demographics, clinical characteristics, medication prescribed, baseline health care utilization, and obesity-related complications were described by PNA status. PNA was defined as no pharmacy claim for the AOM within 60 days of the date of the new prescription order as identified in electronic health record data. A multivariable logistic regression model was used to examine factors associated with PNA. RESULTS: The study sample included a total of 1,563 patients. The mean body mass index was 38.4 kg/m2; 10.7% were prescribed liraglutide 3.0 mg, 26.0% were prescribed lorcaserin, 36.3% of patients were prescribed naltrexone-bupropion, 5.4% were prescribed orlistat, and 21.6% were prescribed phentermine-topiramate. Most patients (91.1%) exhibited PNA, with only 8.9% filling their newly prescribed AOM within 60 days. Both the adherent and nonadherent groups were predominately female sex, White, and covered by commercial insurance. The mean age was similar between the 2 groups. Most obesity-related complications were less prevalent in the adherent group, although the Charlson comorbidity index score was similar between the 2 groups. After adjustment for patient demographics and clinical characteristics, there was not a statistically significant association between the specific AOM and PNA (P = 0.299). Patients with depression or living in the Midwest or South regions were at significantly increased risk of PNA. CONCLUSIONS: The rate of PNA to AOMs was very high, suggesting barriers in effective medical management of patients with overweight and obesity. Future research is warranted to understand reasons for PNA to AOMs and how to address these barriers. DISCLOSURES: Dr Kan, Dr Bae, Dr Dunn, and Dr Ahmad are employees of Eli Lilly and Company. Ms Buysman and Dr Gronroos are employees of Optum. Dr Swindle was an employee of Optum at the time the study was conducted and is currently employed at Evidera. Dr Bengtson is employed at Boehringer Ingelheim Pharmaceuticals, Inc. (Boehringer Ingelheim has no connection to this study), and during the conduct of this study was employed at Optum.

103-LB: Impact of Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) in COVID-19 Patients with Preexisting Type 2 Diabetes (T2D) and Cardiovascular Disease (CVD)

Objective: CVD is the leading cause of death and disability among individuals with T2D. National guidelines recommend an SGLT2i or GLP-1 RA in patients with T2D who have or are at high risk for CVD. This study examined the impact of SGLT2i or GLP-1 RA on clinical outcomes in patients with pre-existing T2D+CVD who developed COVID-19. Methods: Adult patients with T2D+CVD who developed COVID-19 during 03/01/20-05/31/22 and had ≥1 year of health plan enrollment before the COVID-19 diagnosis were identified from the Healthcare Integrated Research Database (HIRD®). Eligible patients were classified as guideline concordant or not based on SGLT2i or GLP-1 RA prescription fills in the year before COVID-19 infection. COVID-19 related and all-cause hospitalization, ICU admission, and mortality were compared between SGLT2i or GLP-1 RA users and non-users. Propensity score (PS) matching and multivariable analyses were performed. Results: A total of 42,646 COVID-19 patients with T2D+CVD were identified with a mean follow-up of 8.6 months. The use of SGLT2i or GLP-1 RA was low (n=8,498; 20%). Patients receiving SGLT2i or GLP-1 RA were younger, had fewer comorbidities, took more CVD prevention medications, and were less likely to be hospitalized during the year before COVID-19 infection than non-users. After PS matching and multivariable adjustment, T2D+CVD patients with COVID-19 who received SGLT2i or GLP-1 RA were 12% less likely to be hospitalized and 10% less likely to be admitted to the ICU due to COVID-19 compared to those who did not (n=8,479 each group; both p<0.05). Reductions were also observed for all-cause hospitalization (6%), ICU admission (7%), and mortality (10%), but the results were not statistically significant. Conclusion: The findings suggest that SGLT2i and GLP-1 RA may improve outcomes in T2D+CVD patients with COVID-19 and support existing national guidelines. Disclosure C. Nguyen: Employee; HealthCore Inc. C. L. Crowe: Employee; HealthCore Inc. E. Kuti: Employee; Boehringer Ingelheim Inc. B. M. K. Donato: Employee; Boehringer Ingelheim Pharmaceuticals Inc. R. L. Djaraher: None. L. J. Seman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. N. Graeter: None. T. P. Power: None. V. Willey: Other Relationship; Novo Nordisk A/S. Funding Boehringer Ingelheim

83-OR: Defining the Transcriptome and Epitranscriptome of the ß-Cell Compensation to Insulin Resistance

Type 2 diabetes (T2D) is characterized by decreased functional β-cell mass and poor compensation to insulin resistance. Thus, understanding of the mechanism(s) responsible for the physiological adaptation of β-cells to states of high metabolic demand is desirable. We aimed to dissect the transcriptome and m6A mRNA methylation landscape in the β-cell adaptation to insulin resistance. To this end we conducted RNA-sequencing in sorted β-cells and m6A-sequencing in whole islets from three mouse models: a) a dietary model (60% high-fat diet: Control-HF), b) a genetic model (liver-specific insulin receptor KO mouse on chow: LIRKO-C), and c) a superimposed dietary and genetic model of insulin resistance (LIRKO on a high fat diet: LIRKO-HF). These data were compared to littermate controls fed a chow diet (Control-C). Control-HF, LIRKO-C and LIRKO-HF each presented an increase in insulin resistance compared to Control-C. However, LIRKO-C and LIRKO-HF presented a robust insulin secretion capacity and a graded increase in β-cell proliferation and mass compared to Control-C. First, we correlated the transcriptome with surrogates of β-cell adaptation such as insulin secretion, β-cell mass or proliferation. Next, we intersected the genes that positively correlated with β-cell compensation with single-cell RNA seq datasets performed in islets from humans with or without T2D. This bioinformatics analyses identified extracellular matrix (ECM) as the most enriched pathway in the β-cell adaptation to insulin resistance. On the other hand, m6A-sequencing of Control-C, LIRKO-C and LIRKO-HF islets and the intersection of this dataset with the differentially methylated genes in human T2D islets, revealed enrichment in pathways associated with chromatin modifications. Together, these results point to ECM pathways as being important in the transcriptomic remodeling and that m6A acts on chromatin-modifying enzymes in the β-cell compensation to mammalian insulin resistance. Disclosure D.F.De jesus: None. Z.Zhang: Research Support; SinoVac. J.Wei: None. N.K.Brown: None. J.Hu: None. S.Kahraman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. E.Dirice: None. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding American Diabetes Association (7-21-PDF-140 to D.F.DJ.); National Institutes of Health (R01067536)

746-P: Semaglutide Increases the Proportion of People with T2D Achieving a Metabolic Composite Endpoint

Hyperglycemia, high BP and dyslipidemia are common risk factors for CVD. The aim of this study was to assess the proportion of participants treated with once-weekly (OW) semaglutide, or a comparator, achieving a metabolic composite target endpoint in the SUSTAIN trials. Participants from SUSTAIN 1-5, 7-10 and SUSTAIN China with uncontrolled T2D treated with OW semaglutide vs comparators (incl. placebo) were pooled, and the proportion achieving the endpoint (HbA1c <7%, BP <140/90 mmHg and non-HDL cholesterol <130 mg/dL) was assessed. Endpoints were analyzed using on treatment without rescue medication data for each trial, using a binomial logistic regression model with treatment, region/country, and stratification factor as fixed effects and baseline value (HbA1c/BP/Non-HDL) as covariate. Pooled analysis was conducted using logistic regression with treatment and trial as fixed effects and baseline value as covariate. Treatment with 0.5 and 1 mg OW semaglutide was associated with higher odds (OR range 1.4-24.4) of achieving the endpoint vs comparators (Figure). The proportion of participants reaching the composite endpoint across all trials was 24% and 32% for 0.5 mg and 1.0 mg semaglutide, respectively, vs 11% for comparators (p<0.0001). The results indicate that OW semaglutide may assist with the co-management of T2D and cardiometabolic risk factors, which could reduce the risk of CVD in people with T2D. Disclosure L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. C.H.Sorli: Employee; Acerus Pharmaceuticals. A.Ahmann: Advisory Panel; Medtronic. B.Ahrén: Speaker's Bureau; Novo Nordisk, Nestlé Health Science, Stock/Shareholder; Novo Nordisk, AstraZeneca, Eli Lilly and Company. M.Capehorn: Advisory Panel; Novo Nordisk, Lilly Diabetes, Boehringer Ingelheim Pharmaceuticals Inc., Research Support; Boehringer Ingelheim Inc., Novo Nordisk, Lilly, Speaker's Bureau; Novo Nordisk, Lilly, Boehringer Ingelheim Inc. P.Hu: Employee; Novo Nordisk (China). I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp & Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. W.Liu: Employee; Novo Nordisk (China). H.W.Rodbard: Advisory Panel; Merck Sharp & Dohme Corp., Pacira BioSciences, Inc., Research Support; Eli Lilly and Company, Medtronic, Sanofi, Novo Nordisk. Z.Shen: Employee; Novo Nordisk (China).

123-LB: Implementing a Multidisciplinary Model of CGM Care in Real-World Pharmacy Practice—A Clinical Consensus for Canadian Pharmacists

Background: Continuous glucose monitoring (CGM) devices have transformed diabetes care, but there is a lack of guidance for pharmacists to follow when onboarding patients to begin using CGM systems. Our study aimed to develop a blueprint for best practices for pharmacists to support people living with diabetes (PWD) using CGM systems. Methods: We used a modified DELPHI process to gather insights from 11 Key Opinion Leaders (KOLs) across Canada, including two endocrinologists, one family physician, and eight pharmacists. Consensus was reached for each criterion when 75% agreement was achieved. Criteria for CGM device initiation, short-term or episodic CGM use, and best practices for CGM onboarding and monitoring were developed based on the results. Results: Amongst the ideal candidates for CGM use are PWD using insulin, those with type 1 diabetes, individuals not reaching their A1C target, those experiencing frequent hypoglycemia, pregnant individuals, and others at risk of hypoglycemia. Best practices for onboarding and monitoring included shared decision-making conversations, a comprehensive overview of cost and coverage options, customized alerts and alarms, and timely follow-up sessions. Discussion: The KOL group ensured a comprehensive and diverse perspective. The developed blueprint provides a valuable resource for pharmacists to improve the use of CGM devices and enhance diabetes management for their patients. Incorporating these best practices into clinical practice has the potential to transform diabetes care and improve outcomes. Disclosure A. S. Sihota: Consultant; Novo Nordisk Canada Inc., Other Relationship; Becton, Dickinson and Company. S. Sivapalan: Advisory Panel; Novo Nordisk, Pfizer Inc., AstraZeneca, Consultant; Pear Healthcare Solutions Inc., Other Relationship; Boehringer Ingelheim (Canada) Ltd., GlaxoSmithKline plc., Novo Nordisk, Bristol-Myers Squibb Company, Pfizer Inc., AbbVie Inc., Ferring Pharmaceuticals, AstraZeneca. T. Smith: Advisory Panel; Novo Nordisk Canada Inc., Dexcom, Inc., Emergent Biosolutions. I. Halperin: Advisory Panel; Sanofi, Speaker's Bureau; 3Boehringer Ingelheim Canada Ltd. /Ltée, Abbott Diabetes, Dexcom, Inc., Novo Nordisk. A. B. Jain: Advisory Panel; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bayer Inc., Insulet Corporation, Takeda Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Research Support; Abbott, Amgen Canada, Novo Nordisk, Speaker's Bureau; Abbott, Amgen Canada, Dexcom, Inc., AstraZeneca, Novo Nordisk, Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Pfizer Inc. A. Chin: Other Relationship; Abbott Diabetes, BMO Bank of Montreal, Diabetes Canada, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care, Inc., Research Support; Novavax, Centricity Research. W. Chow: Advisory Panel; GlaxoSmithKline plc., Pfizer Inc., Speaker's Bureau; Abbott Diagnostics, AstraZeneca, Bayer Inc., Bausch Health, Canada, Boehringer Ingelheim (Canada) Ltd., Eisai Inc., Novo Nordisk. S. Jin: Advisory Panel; Dexcom, Inc., Eisai Inc., Novo Nordisk Canada Inc., Board Member; Wounds Canada, Consultant; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals Inc., Canadian Collaborative Research Network, Diabetes Canada, GlaxoSmithKline plc., HLS Therapeutics Inc., MDBriefcase, Novo Nordisk Canada Inc., AstraZeneca, Speaker's Bureau; Eisai Inc., Dexcom, Inc., Novo Nordisk Canada Inc. T. Molberg: None. S. Patil: None. R. Siemens: Consultant; Canadian Collaborative Research Network, Novartis Canada, AstraZeneca, Montmed, Sanofi, MDBriefcase, Other Relationship; Abbott Diabetes, Amgen Canada, Boehringer Ingelheim and Eli Lilly Alliance, GlaxoSmithKline plc., HLS Therapeutics, Novo Nordisk, Dexcom Canada, Diabetes Canada. Funding Dexcom Canada

870-P: Empagliflozin and the Risk of Gout—Analysis from the Empagliflozin Comparative Effectiveness and Safety (EMPRISE) Study

Hyperuricemia is frequently observed in patients with type 2 diabetes (T2D) and is associated with increased risk of gout. Empagliflozin lowers serum urate levels by enhancing its urinary excretion. Using claims data from 2 commercial insurance datasets and Medicare (2014-2019), we evaluated the association between treatment with empagliflozin and the risk of incident gout in routine clinical practice. After excluding patients with a history of gout or gout medications, we identified 102,262 pairs of 1:1 propensity score-matched adults with T2D initiating empagliflozin or a DPP4 inhibitor (DPP4i) (Cohort 1), and 131,216 pairs initiating empagliflozin or a GLP-1 receptor agonist (GLP-1RA) (Cohort 2). We estimated pooled HR and RD/1,000 PY with their 95% CI adjusting for 141 baseline covariates and conducted stratified analyses within multiple subgroups (Table). Over a mean follow-up of ~8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared with patients initiating DPP4i [HR, 0.69 (0.60, 0.79); RD -2.27 (-3.08, -1.46)] or GLP-1RA [HR 0.83 (0.73, 0.94); RD -0.99 (-1.66, -0.32)]. Results were consistent within sex, age, BMI, HF, CKD subgroups and among users of diuretics (Table). In clinical practice, the initiation of empagliflozin was associated with a lower risk of incident gout compared with the initiation of DPP4i or GLP-1RA. Disclosure H.Tesfaye: None. J.M.Paik: None. L.Zabotka: None. P.T.Htoo: Employee; Johnson & Johnson. N.Schmedt: Employee; Boehringer Ingelheim International GmbH. L.Koeneman: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.J.Seman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. D.J.Wexler: Other Relationship; Novo Nordisk A/S. E.Patorno: Research Support; Boehringer Ingelheim Inc., National Institutes of Health, Patient-Centered Outcomes Research Institute, US Food and Drug Administration.

1619-P: Creation of a Mouse Model That Phenocopies Human MODY8—A Valuable Tool to Interrogate Exocrine–Endocrine Cross Talk

Despite the intimate anatomical relationship between the two compartments of the pancreas, little is known about the biological components mediating the exocrine-endocrine communication in regulating glucose homeostasis. Maturity-onset diabetes of the young, type 8 (MODY8) is a dominantly inherited autosomal form of monogenic diabetes, caused by heterozygous mutations in the carboxy ester lipase (CEL) gene expressed in acinar cells. MODY8 is characterized by chronic pancreatitis (CP) and exocrine dysfunction from childhood, followed by diabetes in adulthood. Heterozygous MODY8 mice develop CP but are normoglycemic. Here, we report a refined mouse model that bears the mutation present in MODY8 patients on one allele, and the humanized normal variable number of tandem repeat (VNTR) of CEL with 16 repeats (16R) on the other, mimicking the genetic make-up seen in MODY8 patients. This mouse model (MODY8/16R) acts as a unique tool to directly interrogate the dynamic communication between the exocrine and endocrine compartments by phenotyping longitudinally from weaning to age 2 yrs. Preliminary histopathological analyses of the pancreata reveal features of CP in some lobes, including inflammation, fibrosis and fat infiltration, mirroring the disease in humans. Moreover, confocal microscopy showed the presence of zymogen granules containing mutant CEL within beta cells. These data argue that the mutant CEL protein is transferred from acinar cells to beta cells in pathological conditions, with implications of directly impacting beta cell viability. Examination of glucose homeostasis revealed that inducing stress (e.g. a high-fat diet) leads to glucose intolerance in MODY8/16R mice compared to their control littermates. In conclusion, the availability of a MODY8/16R mouse model provides a unique opportunity to carefully characterize the endocrine-exocrine communication in the pancreas in a longitudinal manner that is otherwise not possible in humans. Disclosure K.El jellas: None. S.Kahraman: Employee; Boehringer Ingelheim Pharmaceuticals Inc. M.E.Lowe: Other Relationship; MilliporeSigma, Wolters Kluwer Health. A.Molven: None. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding National Institutes of Health (U01135095)

An online survey among US patients with immune-mediated conditions: Attitudes about biosimilars.

BACKGROUND: Few surveys about biosimilars have been conducted among US patients. OBJECTIVE: To evaluate attitudes about biosimilars among patients with rheumatoid arthritis (RA), psoriasis and/or psoriatic arthritis (PsO/A), and/or inflammatory bowel disease (IBD). METHODS: WebMD, LLC fielded a 16-item online survey to members of the US Dynata consumer panel meeting these criteria: aged 18 years or older; self-reported specialist diagnosis of RA, PsO/A, or IBD of at least 1 year; and not currently receiving an infliximab biosimilar. A quota of 500 was set, stratified by region and condition. The survey was exempt by the institutional review board, exploratory, and not registered. RESULTS: Overall, 44% (n = 221) of patients were on a biologic; 56% (n = 279) were not on a biologic (40% [n = 199] were biologic naive and 16% [n = 80] used biologics in the past). Among all patients, 66% were unaware of biosimilars and 24% were aware (10% unsure). After being shown the US Food and Drug Administration definition of a biosimilar, main concerns were side effects (59%), long-term safety (50%), and not knowing a lot (46%). Among current users, 43% would switch to a biosimilar and 26% would not (32% unsure). Of those unwilling to switch, 51% were concerned about side effects, 42% about financial support, and 40% about efficacy. When those not on a biologic were asked if their doctor prescribed an original anti-tumor necrosis factor α but their insurance required its biosimilar, 49% would switch and 8% would not (43% unsure). 51% of patients surveyed thought pharmacist-level substitution of an interchangeable biosimilar was acceptable with notification. Survey findings were consistent among the RA, PsO/A, and IBD subgroups. CONCLUSIONS: Although two-thirds of patients surveyed were unaware of biosimilars, the majority were potentially receptive to biosimilar treatment after being provided with the definition of a biosimilar. Patients expressed a desire to know more about biosimilars in general, how they compare with original biologics, their benefits, and cost. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals Inc. (BIPI). WebMD, LLC, fielded the survey. BIPI was given the opportunity to review the article for medical and scientific accuracy and intellectual property considerations. Dr Gibofsky is a consultant/advisor for AbbVie Inc., Biosplice Therapeutics, Lilly, Novartis Pharmaceuticals Corporation, and Pfizer Inc., and he is on the speakers' bureau for AbbVie Inc., Amgen, Lilly, and Pfizer Inc., and has stock ownership in AbbVie Inc., Amgen, Bristol-Myers Squibb Company, Horizon Pharma plc, and Pfizer Inc. Dr Peyrin-Biroulet reports that he has received personal consulting fees from Merck Sharp & Dohme, AbbVie, Janssen, Takeda, Celltrion, Pfizer, Bristol-Myers Squibb Company, Pharmacosmos, Shire, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, UCB-Pharma, Hospira, BIPI, and Lilly. Dr McCabe is an employee of BIPI. Dr McGrath was an employee of BIPI at the time the survey was conducted. Mr Jacobson, Mr Franklin, and Ms O'Hara-Levi report no disclosures.

Real-world impact of empagliflozin on total cost of care in adults with type 2 diabetes: Results from an outcomes-based agreement.

BACKGROUND: Value-based health care is expanding through payment models such as outcomes-based agreements between manufacturers and payers. OBJECTIVE: To describe the total-cost-of-care outcomes of an outcomes-based agreement evaluating the real-world impact of empagliflozin vs other type 2 diabetes mellitus (T2DM) drugs among all patients with T2DM, with and without cardiovascular disease (within and beyond the requirement of the agreement). METHODS: In this prospective real-world analysis, members from the health plan of an integrated health care delivery system from the commercial and Medicare Advantage lines of business, who qualify under the confines of the contract, were included for analysis. Thus, members aged 18 years and older who were continuously enrolled in the identification (January 1, 2018, to December 31, 2018) and measurement periods (≤1 year post-index) with a T2DM diagnosis were retained. Patients using empagliflozin and empagliflozin-combination drugs constituted the empagliflozin group; those using all other antihyperglycemics, the nonempagliflozin group. Patients with type 1 diabetes, or those using metformin or insulin monotherapy, at index were excluded. Eligible members were followed for up to the earliest occurrence of disenrollment date, discontinuation (60-day medication fill gap allowed) of empagliflozin (or nonempagliflozin containing) medication, or the end of the measurement period. We compared, using Student's t-test and summary statistics (for reporting the outcomes agreement) and a propensity-matched difference-in-difference model (for the followup evaluation beyond the requirement of the agreement), the mean all-cause total cost of care (pharmacy plus medical) per patient per month (PPPM) between the 2 groups, including a subgroup of members with a baseline cardiovascular disease diagnosis. RESULTS: There were 4,577 (3,069 and 1,508 in the commercial and Medicare) and 33,712 (15,571 and 18,141 in the commercial and Medicare) in the empagliflozin and nonempagliflozin groups, respectively. The difference in mean total cost PPPM was $75 lower for empagliflozin vs nonempagliflozin groups, driven mainly by lower medical costs in the empagliflozin group (-$465 PPPM). However, the difference was not statistically significant in the propensity score-matched model. CONCLUSIONS: Although empagliflozin had higher pharmacy costs, the total cost of care for patients with T2DM and with established cardiovascular disease were comparable to the group of patients with all other T2DM, driven mainly by lower medical costs. DISCLOSURES: The authors report no conflicts of interest beyond being employees of the 2 organizations involved in this outcomes-based agreement. Ms. Palli is a former employee of Boehringer Ingelheim Pharmaceuticals, Inc., who was affiliated at the time of study conduct.

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.

Endothelin Receptor Antagonists for Kidney Protection: Lessons from the SONAR Trial.

Endothelin Receptor Antagonists for Kidney Protection: Lessons from the SONAR Trial.

994-P: DINAMO—Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents with Type 2 Diabetes (T2D) : Innovative Study Design and Baseline Characteristics

T2D in youth remains challenging to manage and there is need for an expanded treatment armamentarium. The DINAMO study was designed to overcome recruitment difficulties that plagued previous T2D studies in youth. Within 3 years, DINAMO enrolled 158 patients aged to &amp;lt;18 years at 64 sites in 12 countries with HbA1c 6.5-10.5% on metformin and/or insulin. Unique to this study, participants with a modifiable exclusion initially could be re-screened up to 5 times. Patients were randomized to linagliptin (5 mg) , empagliflozin (mg) , or placebo (1:1:1) . At week 12, 50% of empagliflozin patients who could not attain HbA1c &amp;lt;7.0% were re-randomized to either remain on mg or increase to 25 mg. HbA1c change from baseline to week 26 was the primary efficacy endpoint and safety was evaluated over 52 weeks. The main reason for screen failure was HbA1c out of range (57%) . Baseline characteristics of participants are shown below. The study will be completed in fall 2022. Innovative approaches (e.g., testing multiple agents against a single placebo, re-screening patients with modifiable exclusion criteria, using a consortium model to consolidate efforts of several centers, and creating a Steering Committee to adjust study design) can successfully overcome the challenges of conducting clinical trials in youth with T2D. Disclosure L.M. Laffel: Advisory Panel; Medtronic, Roche Diabetes Care. Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Stock/Shareholder; DreaMed Diabetes, Ltd. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. G.J. Klingensmith: Research Support; AstraZeneca, Novo Nordisk, Takeda Pharmaceutical Company Limited. Stock/Shareholder; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. C. Schroeder: Employee; Boehringer Ingelheim Inc. D. Neubacher: Employee; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. J. Marquard: Employee; Boehringer Ingelheim Inc. P. Zeitler: Consultant; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Takeda Pharmaceutical Company Limited. S.M. Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. Research Support; Jaeb Center for Health Research, Provention Bio, Inc. Other Relationship; National Institute of Diabetes and Digestive and Kidney Diseases. Funding Boehringer Ingelheim

20-OR: The Renal and Vascular Effects of Combined SGLT2 and Angiotensin Converting Enzyme Inhibition

The goal of this mechanistic trial was to determine the kidney and cardiovascular effects of combined treatment with an SGLT2i (empagliflozin 25mg QD) and an ACEi (ramipril 10mg QD) for 4 weeks in patients at risk of renal hyperfiltration. In this randomized, double-blind, placebo-controlled, cross-over trial, measurements were obtained following each of the 4 treatment phases: 1) no treatment, 2) 4-week ramipril treatment alone, 3) 4-week empagliflozin-ramipril combination treatment, and 4) 4-week placebo-ramipril combination treatment. The primary endpoint was GFR after empagliflozin-ramipril treatment compared to placebo-ramipril. At the end of each study phase the following measurements were performed under clamped euglycemia (4-6 mmol/L) : inulin (GFR) and paraaminohippurate (effective renal plasma flow, ERPF) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, non-invasive cardiac output monitoring, plasma and urine biochemistry. Empagliflozin-ramipril treatment resulted in an 8ml/min/1.73m2 lower GFR (p=0.0061) , lower absolute proximal fluid reabsorption rate (p=0.0092) , lower absolute proximal sodium reabsorption rate (p=0.0056) , and lower urinary 8-isoprostane (p=0.0084) relative to placebo-ramipril treatment. Empagliflozin-ramipril treatment resulted in additive blood pressure lowering effects (SBP p=0.0112; DBP p=0.0032) and a lower total peripheral resistance (p=0.0368) . There were no other significant changes observed with the addition of empagliflozin. SGLT2i-ACEi combination treatment resulted in an expected GFR “dip”, suppression of oxidative stress markers, and additive declines in blood pressure and total peripheral resistance in this mechanistic study. These changes are consistent with a protective physiological profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding an SGLT2i to conservative therapy. Disclosure Y. Lytvyn: None. K. Kimura: Employee; 3Boehringer Ingelheim Canada Ltd./Ltée. N. Peter: Employee; Boehringer Ingelheim Pharma GmbH &amp; Co.KG. V.S. Lai: Advisory Panel; Baxter. J. Tse: None. L. Cham: None. B.A. Perkins: Advisory Panel; Abbott Diabetes, Insulet Corporation, Sanofi. Board Member; Novo Nordisk. Research Support; BMO Bank of Montreal, Novo Nordisk. Other Relationship; Abbott Diabetes, Insulet Corporation, Medtronic, Novo Nordisk. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. D. Cherney: Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk, Mitsubishi Tanabe Pharma Corporation, Sanofi. Funding Boehringer Ingelheim and CIHR, Diabetes Canada and the Heart and Stroke Richard Lewar Centre of Excellence and the Heart and Stroke Foundation of Canada

515-P: Harnessing Simulation-Based Corrective Mentoring in Continuing Medical Education to Improve Clinical Decision Making and Identify Persisting Educational Needs

Rationale: Due to the vast number of treatment options and clinical presentations of patients with T2DM, providers are challenged to individualize treatment. Incorporating corrective mentoring into decision-based continuing medical education (CME) is a proven method to improve clinical decision-making while simultaneously elucidating persisting educational needs. Methods: Vindico Medical Education and Syandus partnered to develop four virtual clinical scenarios designed to encourage optimal decision making for patients with T2DM by providing immediate feedback via simulated corrective mentoring. Results: A total of 765 primary care providers (PCPs) and 103 endocrinology providers participated in the simulation. Across all four simulations, only 15% of decisions were optimal on the first selection. At baseline, the most challenging topics were evaluating comorbidities and optimizing the use of SGLT-2 inhibitors (13% and 3% optimal decisions made, respectively) . However, after corrective mentoring, there was a 400% relative increase in optimal decisions made. Relative to PCPs, endocrinology providers were 11% more likely to eliminate non-ideal treatment options for a patient with T2DM, obesity, and ASCVD. Similarly, endocrinologists were 14% more competent than PCPs regarding the use of an SGLT-2 inhibitor for a patient with T2DM and worsening kidney disease. The reason for these findings may be that, relative to endocrinologists, PCPs are nearly twice as concerned with optimizing A1C control versus managing comorbidities such as kidney disease or obesity. Conclusion: The use of corrective mentoring in simulation-based CME is an impactful way to encourage clinical decision-making in alignment with the latest evidence-based care. Moreover, these data highlight the need to educate PCPs on the importance of considering comorbidities when individualizing treatment for patients with T2DM. Disclosure K.Robinson: None. D.Seifert: Other Relationship; Amgen Inc., Merck &amp; Co., Inc. J.Frederick: None. R.A.Esgro: None. Funding Independent Educational Grants from Boehringer Ingelheim Pharmaceuticals, Inc. and Lilly USA, LLC; and Merck &amp; Co., Inc.

P-123 A phase Ia/Ib, open-label, dose-escalation study of the TRAILR2 agonist BI 905711 in combination with chemotherapy in patients with advanced gastrointestinal cancers

Activation of the tumor necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAILR2) induces apoptosis via the extrinsic pathway. Targeting TRAILR2 is therefore an attractive therapeutic strategy in oncology, but some early TRAILR2 agonists showed limited clinical success due to low efficacy or severe hepatotoxicity. The tetravalent bispecific antibody BI 905711 represents a novel, liver-sparing, TRAILR2 agonist, which cross-links TRAILR2 with cadherin 17 (CDH17) to induce CDH17-dependent TRAILR2 oligomerisation. CDH17, a membrane protein highly expressed in gastrointestinal (GI) cancers, is not expressed in normal hepatocytes. Thus, using CDH17 as a liver-sparing anchor may avoid hepatotoxicity while increasing selectivity to cancer cells. In preclinical models of GI cancer, including colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), BI 905711 showed activity both as a single agent and in combination with chemotherapeutic agents (Garcia-Martinez et al., Mol Cancer Ther 2021;20:96–108). Preclinical studies also showed synergism of BI 905711 and SoC chemotherapy, particularly irinotecan. This phase Ia/Ib open-label, multicentre study (NCT05087992) aims to determine the maximum tolerated dose (MTD) and recommended dose for expansion (RDE), pharmacokinetics (PK), and preliminary efficacy of BI 905711 in combination with chemotherapy (FOLFIRI; irinotecan, leucovorin, and fluorouracil) with or without bevacizumab in patients with advanced, refractory GI cancers. Up to 100 patients with histologically or cytologically confirmed, advanced, unresectable or metastatic GI cancers will be enrolled. In phase Ia, approximately 20 patients with CRC will receive intravenous BI 905711 at escalating doses (starting dose 0.6 mg/kg) on day 3 of 14-day cycles, plus FOLFIRI and bevacizumab (5 mg/kg IV infusion over 30 mins) on day 1. BI 905711 dose escalation will be guided by a Bayesian logistic regression model with overdose control based on dose-limiting toxicities (DLTs) during the MTD evaluation period (first two 14-day cycles). BI 905711 will be administered until disease progression, unacceptable toxicities or another reason requiring treatment discontinuation. In phase Ib, patients with CRC or PDAC will be enrolled to one of two dose expansion cohorts. In the CRC cohort, patients who have progressed after prior oxaliplatin-based therapy will be randomised in a 2:1 ratio to receive FOLFIRI and bevazicumab with or without BI 905711. In the PDAC cohort, patients with CDH17-positive PDAC who have progressed after prior platin/gemcitabine-based first-line therapy will receive FOLFIRI plus BI 905711. In both cohorts, BI 905711 will be administered at the RDE determined in phase Ia. A safety run-in will be included in the PDAC cohort to confirm the RDE defined in phase Ia prior to enrolling further patients. Primary endpoints are the MTD based on the occurrence of DLTs (phase Ia), and confirmed objective response (OR) according to RECIST 1.1 (phase Ib). Secondary endpoints include PK assessments (phase Ia), progression-free survival, tumour shrinkage, duration of OR and disease control (phase Ib). Further endpoints include assessment of immunogenic response and pharmacodynamic biomarker modulation (including caspase activation and changes in circulating tumour DNA levels). Patient recruitment is active and the study is ongoing. NCT05087992. Medical writing assistance, supported financially by Boehringer Ingelheim Pharmaceuticals Inc., was provided by Jane Saunders of Ashfield MedComms, an Ashfield Health Company, during the preparation of this abstract. The authors received no direct payment. Boehringer Ingelheim.

858-P: Predictors of HbA1c and Weight Response to Sodium–Glucose Cotransporter 2 Inhibitors (SGLT2i) in the Association of British Clinical Diabetologist (ABCD) UK Nationwide Audit

SGLT2i treatment is associated with weight and Hba1c reduction. Previous work has demonstrated clinical predictors of HbA1c and weight reduction with canagliflozin. We aim to analyse predictors of HbA1c and weight change across the class. Methods: People with type 2 diabetes treated with any SGLT2i in the ABCD nationwide audit and available baseline and follow-up data were included. Multiple linear regression model was used to assess independent predictors of Hba1c and weight change. Analysis was performed using Stata 16. Results: Data for 275individuals were included (n=13925 Empagliflozin, n=106Dapagliflozin, n=2976 Canagliflozin) . Baseline (mean±SD) were: age 59.8±10.5 years, baseline Hba1c 9.1±1.6%, weight 97.7±22.2kg, BMI 33.8±6.9kg/m2 and eGFR 81.8±13.6. Median (IQR) diabetes duration was 8.3 years (4.4-12.7) and follow-up time 1.5 years (0.7-2.7) . 61.3% were men. HbA1c fell by 0.87% (95%CI 0.85-0.89; p&amp;lt;0.01) . Factors associated with greater Hba1c reductions include: older age (ß=0.01, p&amp;lt;0.01) ; shorter diabetes duration (ß=-0.01, p&amp;lt;0.01) ; higher HbA1c (ß=0.65, p&amp;lt;0.01) ; greater weight loss (ß=0.02, p&amp;lt;0.01) ; higher alanine aminotransferase (ALT) (ß=0.005, p&amp;lt;0.01) ; higher baseline eGFR (ß=0.002, p&amp;lt;0.01) and canagliflozin or empagliflozin use (vs. dapagliflozin; p&amp;lt;0.05) . Weight fell by 3.0kg (95%CI 2.2-3.8; p&amp;lt;0.01) . Predictors of greater weight reductions include: older age (ß=0.05, p&amp;lt;0.01) ; lower HbA1c (ß=-0.29, p&amp;lt;0.01) ; higher weight (ß=0.03, p&amp;lt;0.01) or BMI (ß=0.17, p&amp;lt;0.01) and larger HbA1c reductions (ß=0.41, p&amp;lt;0.01) . Empagliflozin was superior to dapagliflozin (p=0.01) - no other differences between drugs were noted. Conclusion: Our models demonstrate that baseline characteristics can help predict clinical outcomes with SGLT2i. Individual patient levels factors appear to provide only weak predictive value but may still be useful in assisting therapeutic choices. Disclosure T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. A. Gallagher: Other Relationship; Dexcom, Inc. S. Sivappriyan: None. K. Dhatariya: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH. R.P. Raghavan: Speaker's Bureau; Novo Nordisk. Other Relationship; Lilly Diabetes, Novo Nordisk. A. Bickerton: None. J. Elliott: Advisory Panel; Abbott. Speaker's Bureau; Abbott, Dexcom, Inc., Insulet Corporation, Novo Nordisk. G. Rayman: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None. Funding The ABCD SGLT2 audits are funded by unrestricted grants from Boehringer Ingelheim, AstraZeneca and Napp Pharmaceuticals

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Sub-stratification of type-2 high airway disease for therapeutic decision-making: A 'bomb' (blood eosinophils) meets 'magnet' (FeNO) framework.

Comparison of early diabetic retinopathy staging in asymptomatic patients between autonomous AI-based screening and human-graded ultra-widefield colour fundus images

Learning ObjectivesUpon completion of this activity, participants will:Compare diabetic retinopathy (DR) severity scores of ophthalmologically asymptomatic people with diabetes between outputs from an artificial intelligence (AI)-based system and human-graded ultra-widefield (UWF) color fundus imaging, according to a clinical study.Compare manual 7F-mask gradings vs UWF full-field gradings and describe the correlation with patient characteristics, according to a clinical study.Describe clinical implications of the comparison between the DR severity scores of ophthalmologically asymptomatic people with diabetes outputs using outputs from an AI-based system and human-graded UWF color fundus imaging, according to a clinical study.Accreditation StatementsIn support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye; (4) view/print certificate.Credit hours1.0Release date:Expiration date:Post-test link:https://www.medscape.org/eye/posttest964708Authors/Editors disclosure informationS.S. has disclosed the following relevant financial relationships: Served as consultant or advisor for Allergan, Inc.; Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis Pharmaceuticals Corporation; Optos; Roche; Served as a speaker or a member of a speakers bureau for Allergan, Inc.; Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos; Roche; Received research funding from Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos; Is employed by or has an executive role as Data Monitoring Chair for Phase 2 study sponsored by Bayer HealthCare Pharmaceuticals; Scientific Committee Member of EyeBio Steering Committee for FOCUS sponsored by Novo Nordisk. Other: Trustee member for Macular Society Scientific/Research Advisory Committee Member for Sight UK, Retina UK, Macular Society.Journal CME author disclosure informationLaurie Barclay has disclosed no relevant financial relationships.

Burden of hospitalization for heart failure in the United States: a systematic literature review.

BACKGROUND: Heart failure (HF) affects approximately 6 million Americans, with prevalence projected to increase by 46% and direct medical costs to reach $53 billion by 2030. Hospitalizations are the largest component of direct costs for HF; however, recent syntheses of the economic and clinical burden of hospitalization for heart failure (HHF) are lacking. OBJECTIVE: To synthesize contemporary estimates of cost and clinical outcomes of HHF in the United States. METHODS: A systematic literature review was conducted using MEDLINE and Embase to identify articles reporting cost or charge per HHF in the United States published between January 2014 and May 2019. Subgroups of interest were those with both HF and renal disease or diabetes, as well as HF with reduced or preserved ejection fraction (HFrEF or HFpEF). RESULTS: 23 studies reporting cost and/or charge per HHF were included. Sample sizes ranged from 989 to approximately 11 million (weighted), mean age from 65 to 83 years, and 39% to 74% were male. Cost per HHF ranged from $7,094 to $9,769 (median) and $10,737 to $17,830 (mean). Charge per HHF ranged from $22,162 to $40,121 (median), and $50,569 to $50,952 (mean). Among patients with renal disease, HHF mean cost ranged from $9,922 to $41,538. For those with HFrEF or HFpEF, mean cost ranged from $11,600 to $17,779 and $7,860 to $10,551, respectively. No eligible studies were identified that reported HHF costs or charges among patients with HF and diabetes. Cost and charge per HHF increased with length of stay, which ranged from 3 to 5 days (median) and 4 to 7 days (mean). CONCLUSIONS: This synthesis demonstrates the substantial economic burden of HHF and the variability in estimates of this burden. Factors contributing to variability in estimates include length of stay, age and sex of the sample, HF severity, and frequencies of comorbidities. Further research into cost drivers of HHF is warranted to understand potential mechanisms to reduce associated costs. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals. Osenenko, Deighton, and Szabo are employees of Broadstreet HEOR, which received funds from Boehringer Ingelheim Pharmaceuticals for this work. Kuti and Pimple are employees of Boehringer Ingelheim Pharmaceuticals. This study was presented in abstract form at the 2020 American Heart Association (AHA) Quality of Care and Outcomes Research (QCOR) 2020 Scientific Sessions (May 15-16, Virtual Meeting).