Helfinstine, David A.

Abstract Rationale Patients with idiopathic pulmonary fibrosis (IPF) living in disadvantaged neighborhoods have worse composite outcomes and pulmonary function. Although the current FDA approved drugs reduce lung function decline and may improve mortality for this progressive and fatal disease, equitable access to therapy remains a challenge, which may be contributing to low antifibrotic uptake. Existing understanding of social determinants of health in IPF is derived from local registries and special subpopulations, such as Veterans. The aim of our study is to investigate the association between neighborhood-level deprivation indicators and both the distribution of patients with IPF and outcomes in a large national database. Methods We performed a retrospective cohort analysis between October 1st, 2014, and December 31st 2022, using the Optum Labs Data Warehouse, a large de-identified administrative claims database. We used claims data from commercial, Medicare Advantage, and Medicare Fee-for-Service enrollees across the United States. Diagnosis of IPF was defined using ICD-9 and ICD-10 codes. Social deprivation index (SDI), assessed at the zip code tabulation area level, was determined based on 7 demographic characteristics from the 2015-2019 American Community Survey. Patients were grouped in quintiles based on SDI at diagnosis, where higher values reflect greater deprivation. Hazard ratios (HR) were calculated for all-cause mortality as primary and hospitalization as secondary outcome. Results A total of 96,143 patients (mean age 75.1 years ± 6.9 years) were included in the study, 23.5% received antifibrotics. As area deprivation increased, proportion of female, Black, and Hispanic patients increased, whereas, proportion of male, White, and Asian patients decreased. Similarly, antifibrotic use declined slightly, while prescription of steroids and oxygen increased with SDI. Residing in most disadvantaged neighborhoods increased risk of hospitalization (HR, 1.13 [95% CI 1.09 - 1.17] and all-cause mortality (HR, 1.15 [95% CI 1.11 - 1.19]) after adjusting for covariates over median follow-up of 301 days and 680 days, respectively. Conclusion Gender and racial disparities were evident among IPF patients who live in resource-limited areas. Our study shows that greater proportion of female, Black, and Hispanic IPF patients were disproportionately represented in more socioeconomically deprived areas. Furthermore, as area-level disadvantage increased, fewer patients received antifibrotics, while more patients were on steroids and oxygen therapy potentially indicating more advanced disease. Moreover, living in disadvantaged neighborhoods was associated with worse all-cause mortality and hospitalizations. Identifying individuals who live in socioeconomically disadvantaged areas is essential to provide equitable care and improve outcomes for this life-threatening disease. This abstract is funded by: None

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrosing interstitial lung disease that continues to have high morbidity and mortality. There are only 3 approved medications, (nintedanib, pirfenidone and nerandomilast) which marginally slow FVC decline and only nerandomilast having some mortality benefit. All three have no effect on quality of life (exacerbations and hospitalizations). There is an urgent need to find more effective treatment options. Since IPF is predominantly a disease of the elderly with a peak prevalence in those 65 and older, it is common for these individuals to have other comorbidities such as Hyperlipidemia (HLD). Interestingly, in a prior small study of IPF patients, there is evidence to suggest clinical benefit from ezetimibe, a medication used to treat HLD. This study aims to further evaluate the clinical benefits of ezetimibe in patients with IPF in a large national cohort. Methods We conducted this study using the Optum Labs Data Warehouse (OLDW). The OLDW contains de-identified administrative claims data, including medical and pharmacy claims and enrollment records. This study used claims data from commercial, Medicare Advantage (MA), and Medicare Fee-for-service (FFS) enrollees between October 1st, 2014, and December 31st, 2021. Diagnosis of IPF was defined using ICD-9 and ICD-10 codes. Patients without a diagnosis of IPF were excluded. P < 0.05 was set to determine statistical significance. Two matched patient cohorts depending on ezetimibe use were defined. Primary outcome was all-cause mortality, and secondary outcome was hospitalizations. Results We identified 7724 patients with IPF. After adjusting for age, age group, gender, race, health plan, year of IPF diagnosis, smoking, diabetes, statin treatment, and antifibrotic treatment, two cohorts were identified and matched, patients treated with ezetimibe (n = 3862) and patients not treated with ezetimibe (n = 3862). Among the patients with IPF treated with ezetimibe, ezetimibe use was associated with a reduction in all-cause mortality (hazard ratio [95% CI]: 0.704 [0.660 - 0.752], p-value: <0.001) and hospitalizations(hazard ratio [95% CI]: 0.907 [0.857 - 0.959], p-value: 0.001) compared to patients not treated with ezetimibe. Conclusion In patients with IPF, treatment with ezetimibe may be associated with improved clinical outcomes. Further studies are necessary to confirm benefits, assess anti-fibrotic effects, and inform implementation in management of IPF. As IPF remains a disease with limited treatment options, repurposing drugs continues to offer an avenue to find affordable, safe and already approved medications for use. This abstract is funded by: None

PURPOSE This national study was undertaken to determine screening mammography rates among transgender and gender diverse (TGD) individuals. METHODS TGD individuals and cisgender women who qualified to receive screening mammography based on American College of Radiology guidelines were identified in the longitudinal OptumLabs Data Warehouse. The primary end point was the percentage of patients who had high rates of screening (>75% recommended screenings). Multivariable analyses were conducted in a matched population of transgender men to cisgender women to identify and adjust for factors associated with high adherence. Individuals were matched at a 1:4 ratio (transgender men: cisgender women) on age, race/ethnicity, year of enrollment in their health care plan, and duration of follow-up. RESULTS This study focused on 10,478 TGD individuals (3,778 transgender men; 1,294 transgender women; 5,406 with gender dysphoria not meeting other TGD criteria, NMOT) and 6,218,369 cisgender women. For transgender men, transgender women, individuals with gender dysphoria NMOT, and cisgender women, high mammography rates were observed in 41.1% (95% CI, 39.5 to 42.6), 7.4% (95% CI, 6.0 to 8.8), 11.9% (95% CI, 11.0 to 12.7), and 38.3% (95% CI, 38.3 to 38.4), respectively ( P < .0001). When transgender men were compared with 15,112 matched cisgender women, an age-based differential association was observed between sex and high mammography rates (interaction P = .0003); compared with cisgender women, transgender men appeared more likely to manifest high rates of screening at age 40-49 years (odds ratios [ORs], 1.38 [95% CI, 1.28 to 1.50]; P < .0001) and 50-59 years (OR, 1.57 [95% CI, 1.35 to 1.81]; P < .0001) but not in the older age groups. CONCLUSION The relatively high rates of screening mammography in cisgender women and transgender men suggest clinicians are offering mammography to individuals who are at average or high breast cancer risk, as compared with cisgender women, and not to transgender women at low risk.

605 Background: Patients with stage I testicular cancer (TCa) have excellent survival, and surveillance after orchiectomy is often preferred. Limited data exist on survivorship outcomes of surveillance versus adjuvant therapy. We compared systemic health outcomes between patients managed with surveillance and those treated with upfront therapy. Methods: Claims data from the OptumLabs Data Warehouse (2007–2022) identified stage I TCa patients managed with surveillance, chemotherapy, or radiation. Adjuvant therapy was defined as chemotherapy or radiation within 4 months of diagnosis with no further therapy. Chemotherapy codes were required within 42 days to ensure multiple cycles were not given. Propensity score–matched cohorts were created using logistic regression. A 3-year analysis evaluated new diagnoses of cardiopulmonary complications, metabolic syndrome, men’s health, psychological, and miscellaneous systemic conditions. Outcomes were stratified by treatment group. Chi-square tests and Cox regression analyses compared survivorship outcomes between adjuvant therapy and surveillance. Results: Eight-hundred forty-two patients had 3 years of coverage: 531 surveillance, 159 chemotherapy, and 152 radiation. No significant differences were found in cardiopulmonary, metabolic, psychological, or other systemic outcomes between therapy and surveillance (Table 1). Men’s health diagnoses were more frequent with chemotherapy (35.2% vs 23.9%, p=0.027) compared to surveillance. However, Cox regression showed no significant time-to-event differences on time-to-event analysis between groups. Conclusions: Adjuvant chemotherapy may be associated with higher rates of men’s health complications (infertility, erectile dysfunction, hypogonadism), but over time the risk is not significantly different than surveillance. Propensity-score matched survivorship outcomes: A) surveillance vs chemotherapy; B) surveillance vs radiation. A) Surveillance (N=159) Chemotherapy (N=159) p value Cardiopulmonary Complications 0.157 Yes 14 (8.8%) 22 (13.8%) No 145 (91.2%) 137 (86.2%) Men’s Health Complications 0.027 Yes 38 (23.9%) 56 (35.2%) No 121 (76.1%) 103 (64.8%) Metabolic Syndrome Complications 0.631 Yes 53 (33.3%) 49 (30.8%) No 106 (66.7%) 110 (69.2%) Miscellaneous Systemic Disorders 0.879 Yes 25 (15.7%) 26 (16.4%) No 134 (84.3%) 133 (83.6%) Psychological Diagnoses 0.401 Yes 29 (18.2%) 35 (22.0%) No 130 (81.8%) 124 (78.0%) B) Surveillance (N=152) Radiation (N=152) p value Cardiopulmonary Complications 0.682 Yes 12 (7.9%) 14 (9.2%) No 140 (92.1%) 138 (90.8%) Men’s Health Complications 0.630 Yes 51 (33.6%) 55 (36.2%) No 101 (66.4%) 97 (63.8%) Metabolic Syndrome Complications 0.086 Yes 42 (27.6%) 56 (36.8%) No 110 (72.4%) 96 (63.2%) Miscellaneous Systemic Disorders 0.650 Yes 25 (16.4%) 28 (18.4%) No 127 (83.6%) 124 (81.6%) Psychological Diagnoses 0.650 Yes 28 (18.4%) 25 (16.4%) No 124 (81.6%) 127 (83.6%)

1530 Background: Regular breast cancer screening reduces mortality. The American College of Radiology (ACR) recommends annual screening mammography for asymptomatic, average risk 1) transgender and gender diverse (TGD) men (individuals assigned female sex at birth but identify as men) age 40+ and with residual breast tissue and 2) TGD women (individuals assigned male sex at birth but identify as women) age 40+ and on gender-affirming hormone therapy for 5+ years. This nationwide study investigated screening mammography in TGD individuals. Methods: Four cohorts were identified with complex algorithms of medical and pharmacy data in the OptumLabs Data Warehouse, a longitudinal, administrative insurance claims database that includes patients with commercial insurance and Medicare Advantage: 1) TGD men, 2) TGD women, 3) individuals with gender dysphoria not meeting other TGD criteria (NMOT), and 4) cisgender women -- all of whom met ACR screening criteria. The primary endpoint was the percentage of individuals with high adherence, defined as completing >75% of recommended screenings; comparisons were made across the cohorts (Chi-square test). Multivariable logistic regression was used to compare adherence between TGD men and cisgender women with adjustment for demographics and with 1:4 matching (on race/ethnicity, age group, year of healthcare plan enrollment, and duration of follow-up). Results: 10,478 TGD individuals (3,778 TGD men; 1,294 TGD women; and 5,406 with gender dysphoria NMOT) and 6,218,369 cisgender women were identified. For TGD men, TGD women, individuals with gender dysphoria NMOT, and cisgender women, high adherence was observed in 41.1% (95% confidence interval (CI): 39.5, 42.6%); 7.4% (95% CI: 6.0, 8.8%); 11.9% (95% CI: 11.0, 12.7%); and 38.3% (95% CI: 38.3, 38.4%), respectively, p < 0.0001. No screening ever in these same populations was observed in 23.6% (95% CI: 22.2, 24.9%); 81.3% (95% CI: 79.2, 83.4%), 72.8% (95% CI: 71.6, 74%), and 35.9% (95% CI: 35.8, 35.9%), respectively, p < 0.0001. When TGD men were matched and compared to 15,112 cisgender women, a differential association was observed between gender and high adherence by age group (p < 0.0001); compared to cisgender women, the likelihood of high adherence in TGD men ages 40-49 (n = 2,472), 50-59 (n = 852), 60-69 (n = 320), and 70+ (n = 134) were as follows: odds ratios (OR‘s): 1.38 (95% CI: 1.28, 1.50), p < 0.0001; 1.57 (95% CI: 1.35, 1.81), p < 0.0001; 0.812 (95% CI: 0.619, 1.065), p = 0.1316; and 1.277 (95% CI 0.835, 1.951), p = 0.2595, respectively. Conclusions: This study found that TGD men manifest relatively high adherence to screening mammography, whereas TGD women and individuals with gender dysphoria NMOT manifest low adherence. Future research should focus on improving breast cancer screening in these underserved populations.

ABSTRACT Background Multiple outpatient therapies have been developed for COVID‐19 in high‐risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population. Methods We performed a retrospective cohort study using de‐identified administrative claims data from OptumLabs Data Warehouse. Patients were included if they were age ≥ 18 years, diagnosed with COVID‐19 between January 2022 and December 2023, and underwent SOT prior to COVID‐19. The primary outcome was 30‐day hospitalization. Stabilized inverse probability of treatment weighting was used to account for potential confounding variables. Results 4192 SOT recipients with COVID‐19 were identified. 1403 received an outpatient COVID‐19 therapy, including anti‐spike monoclonal antibodies ( N = 748, 53.3%), molnupiravir ( N = 327, 23.3%), ritonavir‐boosted nirmatrelvir ( N = 217, 15.5%), or remdesivir ( N = 141, 10.0%). In weighted analysis compared to no treatment, anti‐spike monoclonal antibodies (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.28–0.55; p < 0.001), molnupiravir (HR 0.56, 95% CI 0.36–0.89; p = 0.013), and nirmatrelvir (HR 0.47, 95% CI 0.25–0.89; p = 0.020) were associated with reduced hospitalization risk, while remdesivir (HR 1.00, 95% CI 0.50–1.98; p = 0.992) was not. Hospitalization rates were similar between the treatment agents, apart from remdesivir showing a higher risk compared to anti‐spike monoclonal antibodies. Conclusions Outpatient COVID‐19 therapies were largely associated with improved outcomes among SOT recipients. These treatment agents showed similar rates of 30‐day hospitalization, except for remdesivir. The choice of outpatient COVID‐19 therapy in SOT recipients should primarily account for patients’ individual circumstances and drug‐drug interactions rather than differential therapeutic efficacy. image

PURPOSE: For the past 5 years, most major antiemesis guidelines have included olanzapine-containing regimens among the recommended options for prophylaxis with highly emetogenic chemotherapy (HEC). We analyzed the uptake of olanzapine in clinical practice and the changing composition of multidrug antiemetic regimens. METHODS: A retrospective analysis was performed using an OptumLabs deidentified database of medical and pharmacy claims, which was filtered for patients starting HEC in the interval of 2006 to Q2 of 2021. Descriptive statistics were used to analyze patient characteristics and year-by-year antiemetic prescribing patterns, coinciding with cycles 1 and 2 of chemotherapy. RESULTS: A total of 63,154 distinct patients were included. The median age was 58 years (range, 18-88). Breast (45.2%) and hematologic (20.8%) cancers were the most common diagnoses. In 2016, olanzapine was prescribed to 1.4% of patients with cycle 1 of HEC. Prescriptions increased modestly each year, and by 2021, 13.9% of patients received olanzapine with their first cycle of chemotherapy. An additional 5.7% of patients received olanzapine for breakthrough symptoms or enhanced prophylaxis during cycle 2. In 2021, more than three-quarters of patients were prescribed antiemetics in a guideline-concordant manner, with an olanzapine-containing quadruplet (12.2%), an NK1-receptor antagonist triplet (64.5%), or an olanzapine triplet (suppressed for small sample size). CONCLUSION: Despite inclusion in major antiemesis guidelines, there has been relatively slow uptake of olanzapine for prophylaxis with HEC. This finding highlights the challenges of disseminating information and keeping prescribing systems updated with the newest evidence in supportive oncology.

232 Background: Olanzapine has an important role in preventing and treating nausea and vomiting from highly emetogenic chemotherapy (HEC). This drug, for the last 5 years, has been a component of most major antiemesis guidelines. The aim of the current study was to assess how often olanzapine has been prescribed for patients receiving HEC. Methods: A retrospective analysis was performed using an OptumLabs de-identified clinical database of medical and pharmacy claims. The database was filtered for patients starting HEC in the interval of 2006 to Q2 of 2021. Descriptive statistics were used to analyze patient characteristics and year-by-year antiemetic prescribing patterns, coinciding with cycles 1 and 2 of chemotherapy. Results: A total of 63,154 distinct patients were included. The median age was 58 years (range, 18-88). Over a quarter of the patients identified as Black, Hispanic, Asian, or other. Breast (45.2%) and hematologic (20.8%) cancers were the most common diagnoses. In 2016, olanzapine was prescribed to only 1.4% of patients with cycle 1 of HEC. Prescriptions increased modestly each year, and by 2021, 13.9% of patients received olanzapine with their first cycle of chemotherapy. An additional 5.7% of patients received olanzapine for breakthrough symptoms or enhanced prophylaxis during cycle 2. In 2021, over three-quarters of patients were prescribed antiemetics in a guideline concordant manner, with either an olanzapine-containing quadruplet (12.2%), an NK1 receptor antagonist triplet (64.5%), or an olanzapine triplet (exact number suppressed due to small sample size). Conclusions: The rate of olanzapine prescribing is less than might be expected following its inclusion in major antiemesis guidelines. This finding highlights the challenges of disseminating information and keeping prescribing systems updated with the newest evidence in supportive oncology.