US Patient Population Research Articles

Characterization and Potential Relevance of Randomized Controlled Trial Patient Populations in Revision Total Joint Arthroplasty: A Systematic Review.

Randomized controlled trial (RCT) studies in revision total joint arthroplasty (rTJA) are essential to investigate the effectiveness of interventions. However, there has been limited research investigating how patient cohorts comprising rTJA RCT samples resemble the US patient population undergoing rTJA in terms of demographic and clinical characteristics. Thus, the purpose of this systematic review was to compare the patient characteristics of rTJA RCT cohorts with the characteristics of national patient database cohorts. RCT studies for rTJA were aggregated. Patient demographics in this group were compared against HCUP NIS and ACS-NSQIP patient cohorts. Forty-six RCTs met inclusion criteria. There were 3,780 total patients across 46 RCTs. The average age of patients in the rTJA RCT cohort was 66.4 9.4 while the NIS cohort was 67.3 11.1 (d=0.08, effect size=small). The average BMI of the rTJA RCT cohort was 31.1 5.7 while the NSQIP cohort was 31.7 8.3 (d=0.08, effect size=small). For rTJA, effect sizes for age, BMI, sex, ethnicity, smoking, and diabetes were all small or very small. Overall, the rTJA RCT patient cohort does not differ significantly compared to the general patient population undergoing rTJA. Differences in demographic and clinical characteristics between the rTJA RCT cohort and database cohorts were minimal to small, indicating that these differences are unlikely to impact clinical outcomes.

Cataloging health state utility estimates for Duchenne muscular dystrophy and related conditions

BackgroundDuchenne muscular dystrophy (DMD) is a genetic disease resulting in progressive muscle weakness, loss of ambulation, and cardiorespiratory complications. Direct estimation of health-related quality of life for patients with DMD is challenging, highlighting the need for proxy measures. This study aims to catalog and compare existing published health state utility estimates for DMD and related conditions.MethodsUsing two search strategies, relevant utilities were extracted from the Tufts Cost-Effectiveness Analysis Registry, including health states, utility estimates, and study and patient characteristics. Analysis One identified health states with comparable utility estimates to a set of published US patient population utility estimates for DMD. A minimal clinically important difference of ± 0.03 was applied to each DMD utility estimate to establish a range, and the registry was searched to identify other health states with associated utilities that fell within each range. Analysis Two used pre-defined search terms to identify health states clinically similar to DMD. Mapping was based on the degree of clinical similarity.ResultsAnalysis One identified 4,308 unique utilities across 2,322 cost-effectiveness publications. The health states captured a wide range of acute and chronic conditions; 34% of utility records were extrapolated for US populations (n = 1,451); 1% were related to pediatric populations (n = 61). Analysis Two identified 153 utilities with health states clinically similar to DMD. The median utility estimates varied among identified health states. Health states similar to the early non-ambulatory DMD phase exhibited the greatest difference between the median estimate of the sample (0.39) and the existing estimate from published literature (0.21).ConclusionsWhen available estimates are limited, using novel search strategies to identify utilities of clinically similar conditions could be an approach for overcoming the information gap. However, it requires careful evaluation of the utility instruments, tariffs, and raters (proxy or self).

Developing the EPI Symptom Questionnaire (EPI-SQ): a qualitative study to understand the symptom experience of patients with exocrine pancreatic insufficiency (EPI)

BackgroundSymptom assessment is the key factor in determining disease status and optimal management of exocrine pancreatic insufficiency (EPI). There is a need for a standardized patient-reported outcome (PRO) questionnaire to assess symptoms in patients diagnosed with EPI. The purpose of this qualitative study was to increase understanding of the EPI symptom experience from the patients’ perspective, and to develop and evaluate the content validity of the EPI Symptom Questionnaire (EPI-SQ) in US patients with EPI.MethodsConcept elicitation interviews (Phase I) were conducted to understand the symptom experience in patients with a clinical diagnosis of EPI (i.e., fecal pancreatic elastase value of ≤ 200 mcg/g based on most recent value) due to chronic pancreatitis or pancreatectomy. The EPI-SQ was developed based on the data extracted from Phase I interviews and feedback from clinical experts. Next, separate cognitive interviews (Phase II) were conducted to evaluate participants’ understanding of the instructions, items, response scales, and recall periods of the instrument.ResultsDuring Phase I interviews (n = 21), 19 participants (90%) reported abdominal pain as the most frequent EPI symptom and lifestyle changes were the most frequently endorsed impacts (n = 18; 86%). Phase II results indicated that all participants (n = 7) felt the 12-item EPI-SQ was relevant to their symptom experience and that they understood the items, instructions, and response options as intended.ConclusionThe qualitative data from this study support the content validity of the EPI-SQ in measuring EPI symptom severity in US patient populations diagnosed with EPI.

Validation of the German version of the Asthma Impairment and Risk Questionnaire (AIRQ).

The Asthma Impairment and Risk Questionnaire (AIRQ), a 10-item, equally weighted, yes/no tool assessing symptom impairment and risk of exacerbations in patients with asthma aged ≥12 years, was developed and validated in a US patient population to evaluate varying levels of asthma control. This study aimed to validate the German language version of the AIRQ in patients aged ≥12 years with different levels of asthma control. A cross-sectional, observational, multi-centre study comprising a single visit was conducted in multiple specialised asthma centres and general practices in Germany. A total of 300 patients completed the following measures: 1) Patient Sociodemographic and Clinical Questionnaire, 2) AIRQ, 3) Asthma Control Test (ACT), and 4) Asthma Control Questionnaire (ACQ-6). Logistic regression analyses were conducted to assess the AIRQ score cut points with the greatest predictive validity in discriminating between different control levels relative to a standard of ACT plus prior-year exacerbations or ACQ-6 plus prior-year exacerbations. The German version of the AIRQ demonstrated a robust capability to correctly identify well-controlled versus not well- or very poorly controlled (AUC values of 0.90 or higher) and well- or not well-controlled versus very poorly controlled asthma (AUC values of 0.89 or higher). The German version of the AIRQ is a suitable tool to identify adults with varying levels of asthma control, which in turn can help to accurately identify patients with uncontrolled asthma in clinical practice.

Disparities in Access to Spasticity Chemodenervation Specialists in the United States: A Retrospective Cross-Sectional Study.

The aim of the study is to explore variations in access to spasticity chemodenervation specialists across several geographical, ethnic, racial, and population density factors. This is a retrospective cross-sectional study on Medicare Provider Utilization and Payment Data. Providers with substantial adult spasticity chemodenervation practices were included. Ratios were assessed across geographical regions as well as hospital referral regions. A multivariate linear regression model for the top 100 hospital referral regions by beneficiary population was created, using backward stepwise selection to eliminate variables with P values > 0.10 from final model. A total of 566 providers with spasticity chemodenervation practices were included. Unadjusted results showed lower access in nonurban versus urban areas in the form of higher patient:provider ratios (83,106 vs. 51,897). Access was also lower in areas with ≥25% Hispanic populations (141,800 vs. 58,600). Multivariate linear regression results showed similar findings with urban hospital referral regions having significantly lower ratios (-45,764 [ P = 0.004] vs. nonurban) and areas with ≥25% Hispanic populations having significantly higher ratios (+96,249 [ P = 0.003] vs. <25% Hispanic areas). Patients in nonurban and highly Hispanic communities face inequities in access to chemodenervation specialists. The Medicare data set analyzed only includes 12% of the US patient population; however, this elderly national cross-sectional cohort represents a saturated share of patients needing access to spasticity chemodenervation therapy. Future studies should venture to confirm whether findings are limited to this specialization, and strategies to improve access for these underserved communities should be explored.

Helicobacter pylori testing prior to or at gastric cancer diagnosis and survival in a diverse US patient population.

Gastric cancer (GC) accounts for the greatest disparity in cancer mortality between Black and White Americans. Although clinical trials have shown that Helicobacter pylori (Hp) treatment reduces risk of GC, Hp testing and treatment is not consistently performed in the US, and may offer an opportunity to improve survival. In a diverse retrospective cohort of 99 GC cases diagnosed at Duke University from 2002-2020 (57% Black; 43% white), we examined the association of Hp testing and treatment prior to or at cancer diagnosis with overall survival using Cox regression analyses to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (CIs). Overall, 62% of patients were tested for Hp prior to or at GC diagnosis. Of those, 25% tested positive and were treated < 1 year prior to or at diagnosis, 15% tested positive and were treated ≥ 1 year prior to diagnosis, 6% tested positive without evidence of treatment, and 54% tested negative. Compared to never tested, Hp testing and treatment < 1 year prior to or at diagnosis was associated with a significantly reduced likelihood of death (HR 0.21, 95% CI 0.08-0.58). The benefit of any Hp test and treat prior to or at GC diagnosis was significant even among stage IV patients only (HR, 0.22; 95% CI 0.05-0.96). These findings support Hp testing and treatment for patients at risk of or diagnosed with GC, and suggest Hp treatment may provide an opportunity to reduce GC mortality disparities in the US.

Epigenetic Profiles of Triple-Negative Breast Cancers of African American and White Females

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and appears to have disproportionately higher incidence and worse outcomes among younger African American females. To investigate whether epigenetic differences exist in TNBCs of younger African American females that may explain clinical disparities seen in this patient group. This cross-sectional study used clinical, demographic, DNA methylation (HumanMethylation450; Illumina), and gene expression (RNA sequencing) data for US patient populations from publicly available data repositories (The Cancer Genome Atlas [TCGA], 2006-2012, and Gene Expression Omnibus [GEO], 2004-2013) accessed on April 13, 2021. White and African American females with TNBC identified in TCGA (69 patients) and a validation cohort of 210 African American patients from GEO (GSE142102) were included. Patients without available race or age data were excluded. Data were analyzed from September 2022 through April 2023. DNA methylation and gene expression profiles of TNBC tumors by race (self-reported) and age were assessed. Age was considered a dichotomous variable using age 50 years as the cutoff (younger [<50 years] vs older [≥50 years]). A total of 69 female patients (34 African American [49.3%] and 35 White [50.7%]; mean [SD; range] age, 55.7 [11.6; 29-82] years) with TNBC were included in the DNA methylation analysis; these patients and 210 patients in the validation cohort were included in the gene expression analysis (279 patients). There were 1115 differentially methylated sites among younger African American females. The DNA methylation landscape on TNBC tumors in this population had increased odds of enrichment of hormone (odds ratio [OR], 1.82; 95% CI, 1.21 to 2.67; P = .003), muscle (OR, 1.85; 95% CI, 1.44 to 2.36; P < .001), and proliferation (OR, 3.14; 95% CI, 2.71 to 3.64; P < .001) pathways vs other groups (older African American females and all White females). Alterations in regulators of these molecular features in TNBCs of younger African American females were identified involving hormone modulation (downregulation of androgen receptor: fold change [FC] = -2.93; 95% CI, -4.76 to -2.11; P < .001) and upregulation of estrogen-related receptor α (FC = 0.86; 95% CI, 0.34 to 1.38; P = .002), muscle metabolism (upregulation of FOXC1: FC = 1.33; 95% CI, 0.62 to 2.03; P < .001), and proliferation mediators (upregulation of NOTCH1: FC = 0.71; 95% CI, 0.23 to 1.19; P = .004 and MYC (FC = 0.81; 95% CI, 0.18 to 1.45; P = .01). These findings suggest that TNBC of younger African American females may represent a distinct epigenetic entity and offer novel insight into molecular alterations associated with TNBCs of this population. Understanding these epigenetic differences may lead to the development of more effective therapies for younger African American females, who have the highest incidence and worst outcomes from TNBC of any patient group.

Real-world treatment outcomes in patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who were treated with first-line single-agent ibrutinib vs. chemoimmunotherapy.

e19509 Background: Real-world evidence on Bruton Tyrosine Kinase Inhibitor treatment vs chemoimmunotherapy (CIT) for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) has been limited to certain practice settings; research using a large and more comprehensive data source is warranted. Methods: This retrospective cohort study evaluated treatment outcomes among patients with CLL/SLL treated with first-line (1L) ibrutinib (IBR) or CIT using the US claims data from the Komodo Health payer-complete dataset, derived from &gt;150 private insurers and &gt;140 million insured individuals from 2015 to 2022. This study included adult patients with CLL/SLL who initiated 1L single-agent IBR or CIT (defined as no prior CLL/SLL treatment for ≥12 months in the baseline period) on or after March 2016. Time to next treatment (TTNT) was defined as the time from initiation (index date) of 1L treatment to treatment add-on or switch to a next line of therapy ≥29 days post-index and was compared using Cox proportional hazards models. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Results: A total of 3570 1L IBR- and 2391 CIT-treated patients were included, with the mean age 68 vs 64 years, 63% vs 66% male, and mean Quan-Charlson Comorbidity Index score 2.87 vs 3.05, respectively. Median follow-up was 26 vs 31 months, and 13% vs 26% of patients recorded a next treatment during the study period for IBR and CIT, respectively. At 1-, 3-, and 5-year post-index, the probabilities (95% confidence interval [CI]) of not initiating a new treatment were 92% (91%-93%), 83% (81%-84%) and 76% (73%-78%) vs 88% (87%-89%), 70% (68%-73%) and 56% (53%-60%) for the IBR and CIT cohorts, respectively. After controlling for baseline characteristics, 1L IBR patients were significantly less likely to initiate the next line of therapy during the study period (hazard ratio 0.61, 95% CI 0.54-0.69, p&lt;0.001). Conclusions: 1L single-agent IBR was associated with a significantly lower risk of advancing to next line of treatment compared to CIT in this large claims-based data set, reinforcing real-world effectiveness of 1L IBR for CLL in an insured US patient population. [Table: see text]

Updated analysis: Effect of biweekly dosing schedule of trifluridine-tipiracil (TAS-102) on rates of myelosuppression and maintenance of therapeutic efficacy in patients (pts) with previously treated metastatic colorectal cancer (mCRC).

95 Background: For surgically unresectable metastatic colorectal cancer pts, a continuum of treatment is required to improve the OS of our pts. Oral trifluridine-tipiracil (TAS-102) is FDA approved in refractory mCRC per the RECOURSE trial. As per the FDA insert, the recommended dose is 35 mg/m2 twice daily (maximum = 80 mg/day) on Days 1-5 and Days 8-12 of 28-day cycles commonly resulting in Grade 3-4 neutropenia (38%), dose delays (53%), dose reductions (14%) and requiring G-CSF support (9%). To maintain efficacy and to potentially reduce toxicity, we analyzed an alternative biweekly dosing (Days 1-5 and Days 15-19 q28 days). Methods: A retrospective analysis was completed (2019-2022) at Vanderbilt-Ingram Cancer Center in pts with refractory mCRC and appendiceal cancer (CA) who completed ≥ 12 days of TAS-102 therapy and underwent surveillance imaging every 8-12 weeks. Patient data was assessed for ECOG performance status (PS), prior lines of therapy, the use of bevacizumab and CTCAE grade of treatment-related myelotoxicity. Evaluation of progression-free survival (PFS) was completed in mCRC pts. Results: Forty-three patients met the inclusion criteria, with a mCRC:appendiceal CA ratio of 39:4. The median age = 50 y/o (range 30-80); male:female 23:20; median ECOG PS = 1; median number of prior therapies = 3; and median duration of therapy = 97 days (range: 12-396). Associated grade 3/4 hematologic toxicities included: Neutropenia 39% [Grade 3 (12.2%), Grade 4 (2.4%)]; anemia 36.5% [Grade 3 (12.2%)]. No pts required G-CSF. No incidences of neutropenic fever were reported. Five pts (11.6%) required a dose delay and 3 pts (7%) required a dose reduction due to myelosuppression. In mCRC pts, the median PFS was 2.53 months. To date, 6 pts remain on treatment (range: 97-331). Conclusions: In our updated analysis, biweekly dosing of TAS-102 (35 mg/m2 twice daily; Days 1-5 and Days 15-19 of 28-day cycles) for pts with refractory mCRC and appendiceal CA demonstrated tolerable myelosuppression, while preserving PFS in pts with mCRC. With an improved toxicity profile, this alternative TAS -102 dosing schedule may potentially broaden utilization of TAS-102 in patients with borderline PS and may be a more favorable option for future combination studies. Additional prospective data are needed to validate these findings. To our knowledge, this remains the first analysis of biweekly TAS-102 in a US patient population.

Metrics, baseline scores, and a tool to improve sponsor performance on clinical trial diversity: retrospective cross sectional study

ObjectiveTo develop a measure for fair inclusion in pivotal trials by assessing transparency and representation of enrolled women, older adults (aged 65 years and older), and racially and ethnically minoritized...

Cost impact of different treatment regimens of brolucizumab in neovascular age-related macular degeneration: A budget impact analysis.

BACKGROUND: Brolucizumab is a new anti-vascular endothelial growth factor (anti-VEGF) approved for treating neovascular age-related macular degeneration (nAMD). Multiple treatment regimens are available for treating nAMD. These regimens include manufacturer-recommended regimens, pro re nata (PRN) regimens, and treat-and-extend (T&E) regimens, which are based on clinical practice guidelines and data observed in the real-world clinical setting, classified as real-world evidence (RWE). Most budget impact models predict the financial consequences of adding a new drug to the formulary based on the manufacturer-recommended regimen. With different anti-VEGF treatment regimens being used in nAMD by ophthalmologists, it is OBJECTIVE: To estimate the budget impact of different treatment regimens of brolucizumab in nAMD from a US payer perspective. METHODS: A Microsoft Excel-based budget impact model was developed for different treatment regimens of brolucizumab over a 1-year time frame from a US payer perspective. A separate analysis was performed to estimate the budget impact from a US patient population perspective. Model inputs included drug costs, administration costs, physician visit costs, and disease monitoring costs. Outcomes in the budget impact model included the cost per member per month, annual health plan cost, and the US patient population-based annual cost. Based on the prevalence of nAMD in public and commercial health plans, a scenario analysis was conducted on the US population to account for the differences in the drug cost to the public and commercial payers. Further, 1-way sensitivity analyses were conducted to test model assumptions and uncertainty in model inputs. RESULTS: The addition of brolucizumab to the formulary increased the net budgetary impact under PRN and T&E regimens. The maximum increase in expenditure for a hypothetical health plan with 1 million enrollees was associated with the PRN regimen ($824,696), followed by the T&E regimen ($163,101). In contrast, using the manufacturer-recommended and RWE regimens led to an annual saving of $93,068 and $94,170 for the health plan, respectively. In the US patient population model, the introduction of brolucizumab resulted in savings in the manufacturer-recommended ($30.99 million) and RWE regimens ($31.35 million) but led to an increase in annual expenditures for the PRN ($274.58 million) and T&E ($54.30 million) regimens. CONCLUSIONS: Payers need to evaluate the cost impact of different treatment regimens of existing and new anti-VEGFs when making formulary decisions in nAMD management. DISCLOSURES: Mr Siddiqui, Ms Dhumal, Dr Patel, and Dr LeMasters have nothing to disclose. Dr Kamal has received research funding from Cerevel Therapeutics, served as a consultant to Pfizer/Cytel Inc, and received honoraria from Pharmacy Times Continuing Education. Dr Almony has served as a consultant to Cardinal Health and received honoraria from Pharmacy Times Continuing Education and Prime Education.

Costs of biomarker testing among patients with metastatic lung or thyroid cancer in the USA: a real-world commercial claims database study

ObjectiveThis real-world retrospective database study quantified the costs of biomarker testing in a US population of patients with lung or thyroid cancers.Materials and methodsThe commercial claims IBM Marketscan database, a de-identified real-world dataset, was used to identify patients diagnosed with lung or thyroid cancer between 1/2015 and 12/2019. Eligible patients were 18 years or older with two or more lung or thyroid diagnosis codes. Patients were excluded who had evidence of prior cancer diagnoses. Subgroup analyses evaluated eligible patients with metastatic disease. Descriptive statistics were used to evaluate commercial insurance plan payer and patient out-of-pocket costs for diagnostic testing overall as well as by test procedure code and payer type. Costs were adjusted to 2020 US dollars.ResultsA total of 23,633 patients with lung cancer were eligible, 13,320 of whom had metastatic disease. There were 36,867 patients with thyroid cancer, 2,241 of whom had metastatic disease. Biomarker codes were observed among 68.4/75.8% (lung/metastatic lung) and 18.2/42.3% (thyroid/metastatic thyroid). Few patients had codes for comprehensive biomarker tests (5.2/6.7% lung/metastatic lung, 0.3/2.2% thyroid/metastatic thyroid) Among those with biomarker tests, the median per-patient total payer lifetime costs of all biomarker testing were $394/$462 (lung/metastatic lung) and $148/$232 (thyroid/metastatic thyroid). Total lifetime biomarker costs for payers ranged from a median of $128 (consumer-driven health plans) to $477 (preferred provider organizations). Median lifetime patient out-of-pocket costs were $0.00 for both tumor types and all payer types except for consumer-driven health plans ($12 for thyroid and $10 for metastatic lung).ConclusionsWhile comprehensive testing adds to the cost of biomarker testing, these data suggest the relatively low lifetime cost of biomarker testing for both payers and patients. Costs for biomarker testing should not be a limitation to access among these populations with commercial insurance plans in the US.

Early Relapse within 24 Months after Frontline Systemic Therapy (POD24) Is Associated with Worse Survival in Patients with Marginal Zone Lymphoma: A US Multisite Study

Introduction Marginal zone lymphoma (MZL) is an indolent B-cell non-Hodgkin lymphoma with heterogeneous practice patterns. Early relapse after diagnosis in MZL has been associated with poor outcomes in one European study (Luminari et al, Blood 2019) which included only patients requiring immediate therapy for MZL and defined early relapse as lymphoma progression within 24 months (POD24) from diagnosis rather than from the initiation of systemic therapy. In contrast, many patients with MZL do not require immediate therapy, and time from diagnosis to treatment may be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse (POD24) defined as relapse/progression within 24 months from systemic therapy initiation in a large US cohort. Methods This multicenter, retrospective cohort study of MZL patients treated at 8 US medical centers included patients who were ≥18 years old, diagnosed with MZL from 2010-2020, and had information on treatment at diagnosis. Patients who never received systemic therapy, or those who received only antibiotics, radiation, and surgery were excluded. Patients were grouped into POD24 and non-POD24 groups. The primary endpoint was overall survival (OS). Secondary endpoints were determining the predictive factors for POD24 and cumulative incidence of histologic transformation in POD24 vs non-POD24 groups. Survival analysis according to POD24 was only calculated for patients with events within 24 months (early progressors). For patients without early progression, OS was computed starting from the time of systemic therapy. Patients who were censored or expired before 24 months were excluded from analysis. Results Among the 364 eligible patients with newly diagnosed MZL, 103 (28%) were in the POD24 group and 261 (72%) in the non-POD24 group. Patients in the POD24 group had a higher median age (66 vs 61 years), LDH >ULN (39% vs 25%), lower albumin (26% vs 16%), presence of monoclonal protein (49% vs 29%), and received rituximab monotherapy (R, 67% vs 52%) compared to non-POD24 group. The median OS was not reached in either group, however, the 3- and 5-year OS estimates were 80% and 73% in POD24 group compared to 97% and 91% in the non-POD24 groups, respectively (p<0.001, Figure 1). In order to determine if the POD24 was independently associated with OS, we performed Cox regression analysis. After adjusting for factors associated with OS in the multivariate analysis (age, ECOG PS, MZL subtype, LDH >ULN, first-line treatment regimen), POD24 remained associated with significantly inferior OS (HR=3.69, 95%CI=1.93-7.04, p<0.0001). Regardless of the type of first line systemic therapy (R or immunochemotherapy), POD24 group had significantly inferior OS compared to non-POD24 groups. The 3- and 5-year OS estimates for those receiving R were 80% and 75% in POD24 compared to 96% and 88% in non-POD24 (p=0.007), while the 3- and 5-year OS estimates for those receiving immunochemotherapy were 81% and 69% in the POD24 compared to 97% and 94% in the non-POD24 groups, respectively (p<0.0001, Figure 2). To determine the factors associated with POD24, we performed multinomial logistic regression analysis and found that advanced age (continuous, OR=1.03, 95%CI=1.00-1.05, p=0.04) and elevated LDH (compared to normal LDH, OR=1.96, 95%CI=1.05-3.67, p=0.03) were associated with increased odds of POD24, while those who received immunochemotherapy had lower odds of POD24 (compared to R, OR=0.46, 95%CI=0.25-0.87, p=0.02). The cumulative incidence of transformation was significantly higher in the POD24 group compared to non-POD24 group with 3- and 5-year rate of transformation being 18% vs 0% and 32% vs 1%, respectively (p<0.0001). Conclusions In this study (to our knowledge, the largest dataset to date), we show the prognostic relevance of POD24 in MZL in US patient population. Patients with POD24 regardless of the type of systemic therapy received (R or immunochemotherapy) have poor outcomes. These patients represent a high-risk subset of MZL and need to be prioritized for cellular and experimental therapies. Patients with POD24 have a significantly higher risk for histologic transformation and should be considered for a repeat biopsy at relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparative effectiveness of sacubitril/valsartan versus angiotensin converting enzyme inhibitors/angiotensin receptor blockers in de novo heart failure patients

Abstract Introduction Effective use of pharmacological therapy in de novo heart failure (HF) patients is key for slowing down the progression of HF. Randomised clinical trials have shown sacubitril/valsartan (sac/val), providing superior benefit over renin angiotensin system (RAS) blockade with angiotensin converting enzyme inhibitors (ACEi) in patients with HF with reduced ejection fraction (HFrEF) including de novo HF patients. However, real world evidence is scarce. Purpose To compare the rate of all-cause hospitalisations in a real world de novo HFrEF US patient population after initiating sac/val or initiating or continuing RAS blockade with ACEi or angiotensin receptor blockers (ARB) within one year of index date. Methods This retrospective, non-interventional cohort study included adult de novo HFrEF patients (left ventricular ejection fraction ≤40%), from the Optum Electronic Health Records, from Jan 2016 to Mar 2020 (study period: Dec 2013–Mar 2021) who were prescribed sac/val or ACEi/ARB within 30 days of a new HF diagnosis. Patients either with any history of HF in the prior two years or with prior sac/val treatment were excluded. Index date was defined as the first prescription of sac/val or ACEi/ARB after a new HF diagnosis (≤30 days prior to index). One-to-two greedy propensity score matching was used to balance the study arms on demographics and clinical covariates (medications, LVEF, selected comorbidities). Negative binomial models were used to compare the primary endpoint between treatment groups and across subgroups of interest. The primary endpoint was the rate of all-cause hospitalisations within one year from index. Treatment groups were stratified by age, sex, race, ethnicity, history of myocardial infarction, comorbidities and prior ACEi/ARB treatment. Statistical analyses were conducted using R and SAS software. Results Prior to matching, 3,290 patients were initiated on sac/val, 47,678 on ACEi/ARB and post-matching there were 3,290 patients on sac/val and 6,580 patients on ACEi/ARB. Patients with prior ACEi/ARB treatment in both the groups were 1,597 and 2,806, respectively. Mean age was 63.5 in sac/val and 63.7 years in ACEi/ARB groups. After propensity-score matching, the annual rate (per person-year) of all-cause hospitalisation was lower in sac/val compared with ACEi/ARB group, with incidence rate ratio (IRR) of 0.81 (95% confidence interval [CI]: 0.74–0.90) ≤1 year from index. Similarly, in the ACEi/ARB treatment naïve subgroup, sac/val treatment led to 20% reduction in the primary endpoint (IRR: 0.80, 95% CI: 0.69–0.92) compared with ACEi/ARB. Amongst subgroups, results were consistent for most, with significant reduction seen in all-cause hospitalisation rates with sac/val treatment vs. ACEi/ARB. Conclusion Treatment with sac/val vs. ACEi or ARB significantly reduced the risk of all-cause hospitalisations in this real-world study supporting the first-line use of sac/val in treating de novo HFrEF patients. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG

Direct-acting antiviral retreatment patterns for hepatitis C.

BACKGROUND: Despite the strong efficacy of direct-acting antivirals (DAAs) against the hepatitis C virus, many patients require a second regimen of DAA treatment. However, limited research exists to characterize rates of retreatment across different DAA agents or potential factors that may increase retreatment risk. OBJECTIVE: To characterize patterns and predictors of DAA retreatment among a large, generalizable, commercially insured US population of patients. METHODS: Using the IBM MarketScan Commercial Claims and Encounters data source, this retrospective cohort study examined retreatment patterns among patients receiving DAAs between 2013 and 2019. Descriptive statistics were used to compare patient characteristics predictive of retreatment risk and to examine rates of retreatment in patients initiating different DAA treatments. RESULTS: Among 31,553 DAA users, a total of 1,017 (3.2%) required DAA retreatment. Among the 1,017 patients re-treated, 44 (4.3%) received a third treatment regimen and 2 patients received a fourth treatment regimen. The average total cost for a retreatment regimen was $109,683, with patient out-of-pocket costs totaling $1,287 Patients requiring retreatment had higher rates of hypertension (32.0% vs 26.7%; P < 0.001), diabetes (16.9% vs 11.9%; P < 0.001), coagulopathy (9.9% vs 4.5%; P < 0.001), deficiency anemia (11.1% vs 7.4%; P < 0.001), alcohol abuse (3.3% vs 2.3%; P = 0.038), prior liver transplantation (3.4% vs 2.3%; P = 0.024), and hepatocellular carcinoma (6.1% vs 1.9%; P < 0.001) compared with patients not requiring retreatment. CONCLUSIONS: Although uncommon, some patients receiving DAAs require a second regimen of DAA treatment at substantial cost to both health plans and patients. These patients tend to have more comorbidities and markers of hepatic disease severity. Patients with high retreatment risk may benefit from careful monitoring for occurrences of retreatment.

Alzheimer's disease medication use and adherence patterns by race and ethnicity.

We examined racial and ethnic differences in medication use for a representative US population of patients with Alzheimer's disease and related dementias (ADRD). We examined cholinesterase inhibitors and memantine initiation, non-adherence, and discontinuation by race and ethnicity, using data from the 2000-2016 Health and Retirement Study linked with Medicare and Medicaid claims. Among newly diagnosed ADRD patients (n=1299), 26% filled an ADRD prescription ≤90 days and 36% ≤365 days after diagnosis. Among individuals initiating ADRD-targeted treatment (n=1343), 44% were non-adherent and 24% discontinued the medication during the year after treatment initiation. Non-Hispanic Blacks were more likely than Whites to not adhere to ADRD medication therapy (odds ratio: 1.50 [95% confidence interval: 1.07-2.09]). Initiation of ADRD-targeted medications did not vary by ethnoracial group, but non-Hispanic Blacks had lower adherence than Whites. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Initiation of anti-dementia medications among newly diagnosed Alzheimer's disease and related dementias (ADRD) patients was low in all ethnoracial groups. ADRD medication non-adherence and discontinuation were substantial and may relate to cost and access to care. Compared to Whites, Blacks and Hispanics had lower use, poorer treatment adherence, and more frequent discontinuation of ADRD medication, but when controlling for disease severity and socioeconomic factors, racial disparities diminish. Our findings demonstrate the importance of adjusting for socioeconomic characteristics and disease severity when studying medication use and adherence in ADRD patients.

Alternative biweekly dosing schedule of trifluridine-tipiracil (TAS-102) reduces rates of myelosuppression while maintaining therapeutic efficacy in patients (pts) with previously treated metastatic colorectal cancer (mCRC).

3559 Background: Colorectal cancer remains a significant source of morbidity and mortality within the United States, causing nearly 53,000 deaths in 2021. For unresectable pts, the estimated 5-year survival rate is 14%. Given recent advances in treatment, 50% of pts with mCRC will receive third-line therapy or greater, making optimization of therapy in these settings pivotal. Trifluridine-tipiracil (TAS-102) is FDA approved for third-line or greater in mCRC per the RECOURSE Trial. Standard dosing is 35 mg/m2 twice daily (maximum = 80 mg/day) on Days 1-5 and Days 8-12 of 28-day cycles. This dosing schedule is associated with Grade 3-4 neutropenia (38%), requiring treatment delays (53%), dose reductions (14%) and G-CSF support (9%). To reduce this toxicity while maintaining efficacy, we studied an alternative biweekly dosing (Days 1-5 and Days 15-19 of 28-day cycles). Methods: A retrospective analysis was completed (2019-2021) at Vanderbilt-Ingram Cancer Center in pts with refractory mCRC and appendiceal cancer (CA) who completed &gt; 12 days of TAS-102 therapy. Diagnostic imaging was completed every 8-12 weeks. Patient data was evaluated for lines of prior therapy, ECOG performance status (PS), the addition of bevacizumab, and CTCAE grade of treatment-related myelotoxicity. Evaluation of progression-free survival (PFS) was performed only in mCRC pts. Results: 24 pts met the criteria, with a mCRC:appendiceal CA ratio of 20:4 and Male:Female 13:11. Median age 61.5 yrs (range 31-80); median number of prior therapies 3; median ECOG PS of 1; and median duration of therapy 73.5 days. Hematologic toxicities: Neutropenia 30% [Grade 3 (13%), Grade 4 (0%)]; anemia 17.4% [Grade 3 (8.7%), Grade 4 (0%)]; thrombocytopenia 4.3% [Grade 3/4 (0%)]. No pts required G-CSF. One patient required a treatment-related dose delay (neutropenia), and 2 pts required dose reductions (fatigue). In mCRC pts, the median PFS was 2.3 months. To date, 7 mCRC pts remain on treatment (range: 38-385). Conclusions: In our retrospective cohort analysis, TAS-102 biweekly dosing schedule (35 mg/m2 twice daily; Days 1-5 and Days 15-19 of 28-day cycles) for pts with refractory mCRC and appendiceal CA reduced Grade 3 myelotoxicity without Grade 4 toxicities, while preserving PFS in pts with mCRC. With an improved toxicity profile, this alternative TAS -102 dosing schedule may be a more favorable option for future combination studies. Additional prospective data are needed to validate these findings. To our knowledge, this is the first analysis of biweekly TAS-102 in a US patient population.

Association of proton pump inhibitor use and significant hyponatremia—a US population-based case-control study

Hyponatremia is the most common electrolyte abnormality encountered in clinical practice. Several medications are associated with hyponatremia. Proton pump inhibitors were reported to cause hyponatremia in one large Swedish population-based study and small observational studies or case reports. This article presents the results of a single-center retrospective case-control study based on a US patient population that examined the association between the use of proton pump inhibitors and significant hyponatremia. Cases were 792 hospitalized patients with hyponatremia, extracted from 473,000 patient encounters over 6 years, and matched controls were 774 hospitalized patients with normal serum sodium levels whose risk factors for hyponatremia were comparable to those of the study cases. The results showed that use of proton pump inhibitors for at least 30 days prior to hospital admission was significantly higher in patients with hyponatremia than in patients who had normal serum sodium levels (32.7% vs 23.3%, respectively, odds ratio 1.6, P < 0.001). Also, proton pump inhibitor use was nonsignificantly higher among patients with recurrent hyponatremia in subsequent hospitalizations compared with patients who did not have recurrence of hyponatremia (35.5% vs 30.4%, respectively, odds ratio 1.3, P = 0.13). To our knowledge, no prior US population-based study addressing such an association has been published.

Recognizing and Dismantling Raciolinguistic Hierarchies in Latinx Health.

Latinx individuals represent a linguistically and racially diverse, growing US patient population. Raciolinguistics considers intersections of language and race, prioritizes lived experiences of non-English speakers, and can help clinicians more deftly conceptualize heterogeneity and complexity in Latinx health experiences. This article discusses how raciolinguistic hierarchies (ie, practices of attaching social value to some languages but not others) can undermine the quality of Latinx patients' health experiences. This article also offers language-appropriate clinical and educational strategies for promoting health equity.

REVERCEII (ACCRU-GI-1809): A randomized phase II study of regorafenib followed by anti-EGFR monoclonal antibody therapy versus the reverse sequencing for metastatic colorectal cancer patients previously treated with fluoropyrimidine, oxaliplatin and irinotecan.

TPS213 Background: Regorafenib (R) is an oral multikinase inhibitor that blocks several protein kinases involved in angiogenesis and oncogenesis; it has a survival benefit in refractory metastatic colorectal cancer (mCRC). The current standard (std) treatment in patients (pts) with RAS wildtype (WT) mCRC is sequential treatment with an anti-EGFR antibody (AEA) followed by R. However, R, which is orally administered once daily, may be more convenient and thus preferable for pts than AEA. REVERCE, a Japanese trial, demonstrated a significant 5.8 month (mo.) survival benefit with regorafenib administered prior to AEA compared to the std sequence. Based off these findings, the proposed phase II trial is to confirm the observed survival benefit from regorafenib sequencing prior to anti-EGFR monoclonal antibody therapy in REVERCE in a US patient population. Methods: REVERCEII is an Academic and Community Cancer Research United (ACCRU) network-led randomized phase II study of R (dose escalation from 80mg to 160mg based on tolerance) prior to AEA (R+AEA) compared to standard sequencing (AEA+R) in pts with refractory RAS WT mCRC. Patients are randomized 1:1 to receive R (Arm A) vs. AEA (with or without irinotecan per investigator choice) (Arm B). At the time of disease progression or intolerance, patients will receive sequential treatment until disease progression. Eligibility criteria include histologically confirmed mCRC, ECOG ≤ 2, acceptable organ function, and patients must have had prior fluoropyrimidine, oxaliplatin and irinotecan, and no prior AEA nor R. The primary objective is to compare the overall survival (OS), the primary endpoint, between evaluable patients (eligible, consented, started protocol treatment) who were randomized to R+AEA (arm A) and AEA+R (arm B). With 83 OS events, we have 87% power to detect an improvement in median OS from 9 months to 14.5 mo., assuming 1-sided significance level of 0.15, and exponential distribution. The total sample size is 124 patients. Secondary endpoints include progression-free survival, objective response, and adverse events. The total study duration is expected to be 3 years. Clinical trial information: NCT04117945. Clinical trial information: 04117945.