Higher Healthcare Resource Utilization Research Articles

#1241 Healthcare resource utilisation in adults with chronic kidney disease by KDIGO categorisation in England: 2010-2019

Abstract Background and Aims Chronic kidney disease (CKD) is associated with high clinical burden for patients and substantial economic costs for healthcare systems. Detailed estimates of healthcare resource utilization (HCRU) for patients with CKD in the UK are limited, particularly by stage of CKD. This study assessed outpatient and non-elective inpatient HCRU by stage of CKD in England. Method This non-interventional study utilised data from primary care electronic health records from Clinical Practice Research Datalink (CPRD) AURUM and Hospital Episode Statistics (HES) admitted patient care (APC). Patients aged ≥18 years registered in CPRD with eligible linkage to HES between January 1, 2010 and December 31, 2019 with 2+ eGFR measurement during the period were identified. CKD was defined by eGFR <60 ml/min/1.73 m2 and/or presence of a uACR measurement ≥3 mg/mmol, both confirmed by a second measurement 90-365 days later. Start of follow-up (index) was set to the earliest date during the study period that CKD was confirmed. Follow-up for HCRU ended at earliest of death, administrative censoring, or 31st December 2019. Patients with end-stage kidney disease (eGFR <9 ml/min/1.73 m2) at index were excluded. Number of HCRU events for each HCRU category was estimated as rates per 1,000 person years (PY) for each calendar year based on cumulative number of events. Event rates were calculated as number of outcomes/total time at risk. Confidence intervals (95%) were calculated assuming a Poisson distribution. Age- and sex-adjusted rates were calculated to compare rates across CKD stages. Results Of 6.1 million adult patients meeting study inclusion criteria, 743,945 adults (12.2%) with CKD were identified. Mean age (SD) was 76.1 (11.5) years, 55.2% were female, and 89.8% White, contributing a total of 3,055,600 years of follow-up. Most (60.9%) patients had stage 3a CKD (eGFR 45-<59 ml/min/1.73 m2). Among patients with uACR measurements (44.4%), 48.0% were A1 (<3 mg/mmol), 44.4% A2 (3-30 mg/mmol), and 7.6% A3 (>30 mg/mmol). Overall, per 1000 PY, there were 24,763 primary care visits, 475 non-elective all-cause hospitalisations, 4,950 attended (722 unattended) outpatient visits, including 308 (43 unattended) outpatient nephrology visits and 368.1 attended (61.2 unattended) cardiology visits. For all HCRU categories, greater KDIGO risk category at index was associated with higher HCRU. For example, after age and sex adjustment, patients with CKD stage 3b had a mean of 0.53/PY non-elective all-cause hospitalisations compared to 0.77/PY for patients with CKD stage 4. Additionally, a mean of 5.18 outpatient visits per PY was observed for patients with CKD stage 3b, of which 0.91 were nephrology outpatient visits compared to 8.39 outpatient visits per PY for stage 4, of which 2.65 were nephrology outpatient visits. Generally, both lower eGFR and higher uACR were individually associated with higher HCRU. Conclusion This study demonstrates high HCRU for patients with CKD, with increasing rates of HCRU with lower kidney function and greater kidney damage. Patients with more advanced CKD contribute at a disproportionally higher rate of outpatient healthcare encounters and non-elective hospitalisations. Efforts to prevent the development and progression of CKD and improving clinical outcomes will reduce frequency and cost of HCRU.

#1968 IgA nephropathy and impact of proteinuria and kidney function decline on healthcare resource utilisation among adults in the United Kingdom

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis and can result in kidney failure, especially if left untreated. Proteinuria ≥1.0 g/day is a major risk factor for IgAN progression and rapid kidney function decline. This study describes the characteristics of patients with IgAN in the United Kingdom (UK) and the impact of proteinuria and chronic kidney disease (CKD) stage on healthcare resource utilisation (HRU) and costs. Method In this retrospective, descriptive analysis, eligible patients had at least one code among ICD-9 583.9, ICD-10 N02.8, and ICD-10 N02.9 between 1 October 2015 and 1 October 2022. They were stratified by CKD stage and proteinuria level. CKD stage was defined by ICD-10 N18 code and estimated glomerular filtration rate. Proteinuria level was grouped as low or high by protein excretion rate (<1 g/day vs ≥1 g/day), protein/creatinine ratio (<0.88 g/g vs ≥0.88 g/g), or albumin/creatinine ratio (<100 mg/mmol vs ≥100 mg/mmol). HRU data for 1 year from the index date were obtained from electronic medical records, and costs were obtained from the National Schedule of the National Health Service 2021/22. Weighted average costs were calculated for inpatient, outpatient, and emergency visits. Results We identified 6 940 patients with IgAN. The mean age was 62 years, and most patients (n = 3 980; 57%) were male. For all visit types, HRU (Fig.) and costs (Table) increased with advancing CKD. For all visit types combined, the mean total cost per patient was >23 times higher for CKD stage 5 than stage 1 (£60 259 vs £2 609). Of 2 080 patients with proteinuria data, 560 (27%) had high proteinuria. Annual costs per patient (Table) and the numbers of all visit types (Figure) were higher for patients with a protein excretion rate ≥1 g/day than those with a rate <1 g/day (£12 622 vs £2 822). Conclusion In patients with IgAN in the UK, elevated proteinuria and advanced CKD stage were associated with higher HRU and costs across visit types. Treatments that reduce proteinuria can slow disease progression and prevent rapid decline in kidney function while potentially reducing IgAN-related resource utilisation and costs.

Disease burden and healthcare utilization in pediatric low-grade glioma: a United States retrospective study of linked claims and electronic health records

Abstract Background Despite high long-term survival rates, pediatric low-grade gliomas (pLGGs) are linked with significant tumor- and treatment-associated morbidities that may persist throughout life. The aims of this descriptive cross-sectional pilot study were to characterize health conditions among a cohort of patients with pLGG and explore the feasibility of quantifying disease burden and healthcare resource utilization (HRU). Methods Optum® Market Clarity Data were used to identify patients aged ≤18 years with an ICD-10 code for brain neoplasm, ≥1 physician notes, and with evidence of pLGG recorded between January 1, 2017 – June 30, 2018. Outcomes including health characteristics, HRU, medications, and procedures were assessed at six-month intervals over 36 months. Results 154 patients were identified with pLGG and over half experienced headache/migraine, respiratory infection, pain, or behavioral issues during the 36-month study period. The most common comorbidities were ocular/visual (including blindness), mental health disorders, seizure, and behavioral/cognition disorders. Most symptoms and comorbidities persisted or increased during the study period, indicating long-term health deficits. HRU, including specialty care visits, filled prescriptions, and administered medications, was common; 74% of patients had prescriptions for anti-infectives, 56% antiemetics, and 52% requiring pain or fever relief. Sixty-five percent of patients underwent treatment to control their pLGG, the most common being brain surgery. Little decline was observed in medication use during the study period. Conclusions Patients with pLGG have complex healthcare needs requiring high HRU, often over a long time. Patients need to be optimally managed to minimize disease- and treatment-related burden and HRU.

Burden of Wilson Disease among patients and care partners in the United States: results from a cross-sectional survey

Objective This study assessed the burden of Wilson Disease (WD) among patients and care partners (WD-CPs) in the US and compared it to a US general population of adults (GPs) and care partners (GP-CPs). Methods This cross-sectional, self-reported survey included patients with WD and WD-CPs aged ≥18 years recruited through the Wilson Disease Association (WDA), while data for GPs and GP-CPs were obtained from the 2022 National Health and Wellness Survey. GPs and GP-CPs were propensity score matched (3:1) with WD patients and WD-CPs for demographics and health characteristics. Bivariate analysis evaluated differences in comorbidity burden and health-related outcomes of the WD cohorts compared to matched GP cohorts. Results Thirty-seven patients with WD and 53 WD-CPs completed the survey. Most patients reported some treatment burden (73.3%), experienced sleep problems (60%), and visited a healthcare provider (HCP) in the past 6 months (91.9%). Compared with matched GPs, patients with WD had a significantly higher mortality risk (p < .001) and reported greater rates of chronic liver disease, cirrhosis (both, p < .001), migraines (p = .032), non-alcoholic steatohepatitis (p = .004), sleep problems (p = .009) and HCP visits (p = .002). Most WD-CPs (75.5%) reported high burden of caring (mean ZBI-12 score, 26.5) and more negative impact on esteem than GP-CPs. Conclusion This study highlights the burden of WD experienced by patients and WD-CPs, with patients experiencing high treatment burden, comorbidity burden and healthcare resource utilization, and WD-CPs experiencing high impact of caring, including impact on employment and self-esteem.

Societal and economic burden of migraine in Spain: results from the 2020 National Health and Wellness Survey

BackgroundThe burden of migraine goes beyond the pain and associated symptoms. We aimed to describe the impact of migraine in healthcare resource utilization (HCRU), work productivity, and mood disorders, as well as its economic cost.MethodsCase–control study nested in a cross-sectional analysis of patient-reported data collected between 30/12/2019 and 20/04/2020 as part of the National Health and Wellness Survey, from respondents located in Spain. Adults (≥ 18 years old) who reported a physician diagnosis of migraine and ≥ 1 monthly headache days (MHD) in the previous 30 days were included. HCRU, health-related quality-of-life, depression scores, work and activity impairment, and the associated direct and indirect costs were assessed for four cohorts of migraine patients, according to the frequency of headache (MHD: 1–3, 4–7, 8–14, ≥ 15) and compared to a no-migraine control, matched to migraine cases by a propensity score based on demographic and clinical variables.ResultsThe survey was completed by 595 people with active migraine, of whom 461 (77.4%) experienced < 8 MHDs and 134 (22.6%) ≥ 8 MHDs, and 1,190 non-migraine matched controls. Migraine patients presented worse mental and physical health functioning (SF-12 MCS: 41.9 vs. 44.7, p < 0.001; SF-12 PCS: 48.6 vs. 51.5, p < 0.001), worse self-reported health (EQ-5D VAS: 65.8 vs. 73.5, p < 0.001), more severe depression (PHQ-9: 8.9 vs. 6.1, p < 0.001), and higher overall work impairment (WPAI: 41.4 vs. 25.5, p < 0.001). People with migraine had higher HCRU, twice higher hospitalization rates (17.0% vs. 8.3%, p < 0.001) and 1.6 higher emergency room (ER) visit rates (51.4% vs. 31.2%, p < 0.001). Having migraine translated into higher annual costs with HCRU (€894 vs. €530) and productivity losses (€8,000 vs. €4,780) per person. Respondents with more MHDs presented worse outcomes and higher costs but suffering from 1–3 MHD also increased costs by 51.3%.ConclusionsHaving migraine not only causes a massive impact on patients’ quality of life and ability to work, but it also generates considerable economic costs for society. In Spain, having migraine was associated to 1.7 higher costs per patient. The clinical and economic burden increases with the frequency of headaches but is higher than controls even in patients suffering from 1–3 MHD.Graphical

Healthcare Resource Utilization and Goals of Care Discussions in Patients with Cirrhosis and Acute Kidney Injury.

Patients with cirrhosis and acute kidney injury (AKI) are critically ill and have high health care resource utilization (HCRU). The impact and timing of goals of care discussions on HCRU are not well described. 221 patients enrolled in a prospective cohort study of patients admitted with AKI and cirrhosis were reviewed. Documentation and timing of a goals of care discussions were analyzed as predictors of HCRU, defined as a composite outcome of intubation, initiation of renal replacement therapy, and/or admission to the intensive care unit. Median MELD score was 26 [IQR 19, 33]. 29% patients were listed for liver transplant. 90-day mortality was 61%. 51% patients had at least one HCRU episode. Code status changed from admission to discharge from 91%/7%/0% to 68%/14%18% (full code/do not resuscitate/comfort measures, p < 0.001). 28% patients underwent goals of care discussions, with change in code status at a median of 16 [9, 22] days into admission. Only 18% of discussions were within 7days of admission and all were after an HCRU event. Being listed for liver transplant was not associated with whether goals of care discussions occurred (23% listed vs. 31% non-listed, p = 0.24) but was associated with higher HCRU (69% vs. 43%; p < 0.001). Goals of care discussions occurred late into the hospital course, after episodes of HCRU. Efforts should be made to engage in these discussions earlier in the hospital stay, which may decrease HCRU rates in this critically ill population and align with patients' goals of care.

Cost-utility of Initial Management of High-grade T1 Bladder Cancer With Intravesical BCG vs Immediate Radical Cystectomy

ObjectivesTo compare the cost-utility of initial management of high-grade T1 non-muscle invasive bladder cancer (HGT1 NMIBC) with intravesical BCG versus immediate radical cystectomy. High risk NMIBC patients may climb a costly ladder of treatments, culminating in radical cystectomy for oncologic or symptomatic benefit in up to one-third. This high healthcare resource utilization presents a challenging dilemma in balancing sufficiently aggressive management with cost, toxicity, and quality-of-life. MethodsCost-utility of initially managing HGT1 with intravesical BCG and early radical cystectomy with ileal conduit urinary diversion was compared using decision-analytic Markov models. Five-year oncologic outcomes, adverse event rates, and published utility values were extracted from literature. Costs were calculated from a US Medicare perspective in 2021 US dollars. Sensitivity analysis identified drivers of cost and break-even points for recurrence and progression. ResultsMean costs were $26,093 for intravesical BCG and $39,720 for immediate radical cystectomy, though cystectomy generated a gain of 2.2 QALYs compared to intravesical BCG. Immediate cystectomy was a more cost-effective management strategy for HGT1 NMIBC with an ICER of $7120/QALY.The costs associated with cystectomy, TURBT, and BCG toxicity had the greatest impact on ICER. One-way sensitivity analysis demonstrated that intravesical BCG became a cost-effective management strategy if the five-year recurrence rate of HG T1 was less than 56% or the five-year progression rate to MIBC was less than 4%. ConclusionsAt current prices, treatment of high-grade T1 NMIBC with early radical cystectomy is more cost-effective management strategy than initial treatment with intravesical BCG.

Higher healthcare resource utilization and costs among patients with idiopathic hypersomnia compared with matched controls

Higher healthcare resource utilization and costs among patients with idiopathic hypersomnia compared with matched controls

The comparative burden of chronic spontaneous urticaria, atopic dermatitis and psoriasis in five European countries

AbstractBackgroundSkin diseases can have a significant impact on the physical, psychological and social well‐being of patients. Quantification of the burden of chronic spontaneous urticaria (CSU) compared to other dermatological conditions is limited.ObjectivesTo evaluate the comparative humanistic and economic burden of CSU, atopic dermatitis (AD), and psoriasis (PSO) in five European countries (EU5).MethodsThis cross‐sectional analysis compared data from adult respondents with a physician diagnosis of CSU, AD and PSO from the 2020 National Health and Wellness Survey in EU5 (France, Germany, Italy, Spain and the United Kingdom). Outcomes included Short Form (SF)‐12v2 [mental (MCS) and physical component (PCS) summary scores], SF‐6D, EQ‐5D, EQ‐Visual Analogue Scale (VAS), Dermatology Life Quality Index (DLQI), General Anxiety Disorder‐7 (GAD‐7), Patient Health Questionnaire‐9 (PHQ‐9), Work Productivity and Activity Impairment (WPAI) and healthcare resource utilization (HRU). Multivariable analyses comparing CSU to AD and PSO, respectively, were conducted for each outcome.ResultsThis analysis included 379 CSU, 788 AD and 2,636 PSO patients. Adjusted MCS and PCS scores were lower among CSU patients than AD (MCS, p = 0.006; PCS, p &lt; 0.001) and PSO (p &lt; 0.001 for all). SF‐6D and EQ‐5D scores were consistently lower among CSU patients versus AD and PSO (p &lt; 0.001 for all), whereas the EQ VAS was lower in CSU cohort versus PSO cohort (p = 0.003). Higher DLQI scores were reported in the CSU cohort versus AD and PSO (p &lt; 0.001 for both) and the proportion of patients with anxiety and depression, respectively, (GAD‐7 and PHQ‐9 scores ≥5) was greater among the CSU cohort versus AD and PSO (p &lt; 0.001 for all). Finally, higher HRUs and worse WPAI scores (p &lt; 0.005) were observed in the CSU cohort relative to AD and PSO cohort.ConclusionsCSU is associated with significantly worse health‐related quality of life, more mental comorbidities, negative impact on patients' daily lives and the ability to work, ultimately leading to higher HRU compared with AD and PSO.

P833 Burden of steroid use in patients with moderate ulcerative colitis in Europe and the United States

Abstract Background Steroids are an effective short-term therapy option for induction of remission of ulcerative colitis (UC). However, long-term and frequent steroid use is common in clinical practice despite the risks of complications and adverse events.1 We aimed to describe disease burden in moderate UC patients (pts) based on their steroid use history. Methods Data were drawn from the Adelphi UC Disease Specific Programme™, a cross-sectional survey of gastroenterologists (GIs) and their pts in France, Germany, Italy, Spain, the UK and US from Jan 2020–Mar 2021. GIs reported patient demographics, clinical characteristics, treatments and healthcare resource utilization (HCRU). Pts reported quality of life (QoL) via the EQ-5D, short inflammatory bowel disease questionnaire (SIBDQ), and work productivity and activity impairment (WPAI) questionnaire. Pts had received 5-ASA or immunomodulator with no biologic or Janus kinase inhibitor in the 90 days following treatment initiation, had a history of physician-assessed moderate disease severity or a Mayo endoscopic subscore of 2, and no history of colectomy. Pts were categorized as: no steroids (NS; never received steroids), short term/intermittent (ST/I; currently receiving intermittent steroids or received steroids within the last two years for &amp;lt;90 days), or long term/escalated (LT/E; received steroids for ≥90 days within the last two years or had undergone steroid dose escalation within their current course). Analyses were descriptive. Results Overall, 217NS, 88 ST/I and 172 LT/E pts were analysed (Table 1). Median (interquartile range) total steroid use duration was 4.1 (1.6–22.3) months for ST/I and 14.9 (5.8–36.7) months for LT/E. NS (24.4%), ST/I (25.0%) and LT/E (26.2%) pts experienced abdominal pain; 0.5%, 4.6% and 5.2% had severe/extremely severe pain, respectively. Non-bloody diarrhoea was reported by 16.6%, 14.8%, 20.9% of pts, respectively. In the last 12 months, mean (standard deviation; SD) number of health care visits for NS, ST/I and LT/E was 6.1 (6.2), 7.3 (4.8), 8.0 (7.1); mean (SD) number of tests was 20.8 (17.2), 23.3 (15.7), 25.2 (18.2), respectively. NS, ST/I and LT/E patients reported mean EQ-5D scores (0.85, 0.81, 0.79), SIBDQ total scores (54.6, 49.7, 48.3) and overall work impairment (19.4, 23.1, 27.7). Key comorbidities experienced by ST/I and LT/E were hypertension, depression and diabetes (Figure 1). Conclusion Patients with long-term or escalated steroid use had high symptom burden, frequent comorbidities, high HCRU, and poor QoL. This highlights the need for alternative treatment approaches for moderate UC patients to avoid long-term steroid use. 1. Cross R.K. Inflamm Bowel Dis. 2017;23(10):1689–1701

Risk assessment and real-world outcomes in chronic thromboembolic pulmonary hypertension: insights from a UK pulmonary hypertension referral service

ObjectivesThis study was conducted to evaluate the ability of risk assessment to predict healthcare resource utilisation (HCRU), costs, treatments, health-related quality of life (HRQoL) and survival in patients diagnosed with...

Healthcare Resource Utilization and Costs Among Newly Diagnosed and Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients: A Retrospective Cohort Study Using Contemporary US Claims

Introduction: Prognosis for acute myeloid leukemia (AML) patients is generally poor, with rapid progression and high probability of relapse. AML has previously been associated with high healthcare resource utilization (HRU). Changes in the AML treatment landscape may have impacts on the economic burden of AML: since 2017, seven new systemic therapies have been approved for various AML patient populations, including those unfit for intensive therapy. The frequency of hematopoietic stem cell transplantation (HSCT) has also increased over this period. This retrospective cohort study aims to characterize first-line (1L) and second-line (2L) healthcare resource utilization (HRU) and costs in newly diagnosed (ND) and relapsed/refractory (R/R) AML patients, in the context of newly available AML treatments from 2017-2022. Methods: A large US administrative claims database (Optum) was used to identify ND AML patients between January 1, 2016, and August 31, 2022. The “ND index date” was defined as the first date a non-R/R AML diagnosis code was observed. To confirm that the initial AML diagnosis represented a true case of AML, ≥2 subsequent AML diagnoses within 60 days post-index were required. A washout period of 12 months was used to confirm no previous AML diagnosis. ND patients were required to have continuous enrollment from 1 year prior to the index until at least 30 days after the index date or death, whichever was earlier. A subgroup of R/R patients was then identified: all ND cohort members who 1) had an R/R AML diagnosis code, 2) had continuous enrollment between ND and at least 30 days after the R/R index date, and 3) did not receive 1L HSCT after the ND index date were eligible for inclusion. In this subgroup, the “R/R index date” was defined as the first date an R/R AML diagnosis code was observed. Patient per-patient-per-month (PPPM) HRU and costs were followed through the earliest of HSCT, clinical trial enrollment, death, loss of enrollment, end of data availability (September 30, 2022),or R/R diagnosis (for ND patients only). All results were reported descriptively by line of therapy and treatment received (HSCT vs. non-HSCT). Subgroup analyses were performed by age category. Results: We identified 3,145 ND and 644 R/R AML patients who received treatment over the study period. 3.4% of all treated ND patients received HSCT in 1L (n=107), while 19% of all treated R/R patients received HSCT in 2L (n=122). HSCT patients were younger and healthier than non-HSCT patients, reflecting selection into HSCT treatment by underlying patient characteristics (for ND patients, mean age at diagnosis 71.4 vs. 61.1; Mean Charlson Comorbidity Index (CCI) score 2.8 vs. 2.0; unfit for intensive chemotherapy 69% vs. 36%, Table 1). Patients receiving HSCT in 1L and 2L appeared to have more outpatient encounters (ND: mean 7.4 vs. 5.6; RR: mean 7.5 vs. 6.1, PPPM) than those not receiving HSCT. Number of inpatient days appeared somewhat higher among transplant recipients in 1L, but were similar to non-transplant recipients in 2L ( Table 2). While baseline pre-AML costs increased with age in 1L ($4,478 among patients 75 or older, $3,508 among patients younger than 65, PPPM), 1L follow-up costs were highest in the youngest cohort and lowest in the oldest cohort ($74,083 vs. $40,547, PPPM). Treatment-associated PPPM costs (medical + pharmacy) appeared higher in 1L vs. 2L ($54,457 vs. $48,595). When stratified by transplant status, total PPPM costs for patients receiving HSCT in 1L were higher than for those not receiving HSCT ($74,538 vs. $53,751), driven primarily by higher medical costs ($70,757 vs. $50,283). The same pattern was observed in 2L transplant vs. non-transplant patients ($56,380 vs. $46,979 total costs, $51,712 vs. $41,986 medical costs). Conclusions: The economic burden of AML for both ND and R/R patients in the context of newly available therapies remains substantial. Total costs were comparable but slightly higher for 1L therapy as compared to 2L, and significantly higher among patients receiving HSCT compared to those not receiving HSCT in both 1L and 2L. Decreasing economic burden with age was driven by lower medical costs associated with higher rates of supportive/palliative care, suggesting a lack of available active treatment options among older AML patients.

A Nationwide Analysis of Risks and Outcomes in Hospitalized Patients with Immune Thrombocytopenia and COVID-19 Infection

Background: Insufficient data exists on COVID-19 risks and hospitalization outcomes in patients with immune thrombocytopenia (ITP). Our analysis aims to assess risks and outcomes associated with COVID-19 in ITP patients. Method: In this retrospective study, we obtained data from the National Inpatient Sample (NIS) database for the year 2020. Hospitalizations for ITP were identified using ICD-10 codes, further classified into those with and without COVID-19 infection (Table 1). To account for potential confounding factors, we considered variables such as age, sex, race, zip code-based income quartile, hospital region, hospital teaching status, hospital division, hospital bed size, and insurance status. Additionally, the Charlson index and relevant comorbid conditions such as smoking, alcohol use, illicit drug use, hypertension, diabetes mellitus, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), coronary artery disease (CAD), atrial fibrillation (AF), liver disease, and chronic use of anticoagulants were included. Firstly, univariable logistic regression analysis calculated unadjusted odds ratios (ORs). Then, to adjust for potential confounders, a multivariable logistic regression analysis was performed to calculate adjusted odds ratios (aORs) (Table 2). The multivariable logistic regression model only included variables associated with the outcome of interest in univariable regression analysis at P &amp;lt; 0.1. Proportions were compared using the Fisher exact test, and continuous variables were compared using the Student t-test. All P-values were two-sided, with a significance threshold of .05. Results: Data from 10,831 hospitalizations for ITP in 2020 were gathered. Among those, 563 hospitalizations were of patients with COVID-19. Unadjusted data revealed minimal differences in the mean age between both groups, but there was a statistical difference between COVID-positive and COVID-negative males (48.2% vs. 42.9%) and females (51.8% vs. 57.0%). White race had the highest number of patients in both groups with a statistical difference of 62.5% vs. 68.5%, p=0.000 compared to other races. Moreover, COVID-positive patients with ITP had a significantly higher rate of comorbidities like hypertension (67.8% vs. 60.2%, p=0.000) and diabetes mellitus (38.5% vs. 28.9%, p=0.000). On the other hand, there was no statistical difference between groups with associated comorbidities like smoking, alcohol, illicit drugs, COPD, CHF, CAD, atrial fibrillation, liver disease, and chronic anticoagulation use. ITP patients with COVID-19 showed a significantly longer median length of stay (10.7 days vs. 6.3 days; p=0.000) and higher overall cost-of-hospitalization ($136,915 vs. $98,657; p=0.000). After adjusting for potential confounders using multivariate logistic regression, we found that ITP patients with COVID-19 had notably higher odds of mortality (adjusted odds ratio (aOR) = 5.42, 95% CI: 4.18 to 7.03, p=0.000), longer hospital stays (Coefficient: 4.31 days, 95% CI: 3.31 to 5.30, p=0.000), and increased total hospital charges (Coefficient: $37,243, 95% CI: $20,137 to $54,350, p=0.000). However, there were no statistically significant differences in the administration of PRBC transfusions, platelet transfusions, or immunoglobulin transfusions between the two groups. Additionally, no notable distinctions in the odds ratio of experiencing intracranial bleeding, gastrointestinal (GI) bleeding, myocardial infarction (MI), or acute cerebrovascular accident (CVA) were observed between ITP patients with and without COVID-19. Conclusion: In conclusion, this study highlights the higher risks and poorer hospitalization outcomes associated with COVID-19 in patients with immune thrombocytopenic purpura. The results of our study highlight the significance of taking COVID-19 infection into account when managing and evaluating outcomes in ITP patients, as it seems to be linked to more severe disease manifestations and higher utilization of healthcare resources. Further research and prospective studies are necessary to gain a deeper understanding and address the implications of COVID-19 in this particular patient population.

Incidence of Second Primary Malignancies in Medicare-Insured Patients in the US with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Background As therapeutic advances have increased life expectancy for patients (pts) with relapsed/refractory (RR) multiple myeloma (MM), second primary malignancies (SPMs) have become an increasingly important safety consideration. Prior studies have demonstrated that treatment with alkylators, autologous stem cell transplantation, and immunomodulatory drugs (IMiDs), specifically lenalidomide, are associated with increased risk of SPM. Pts who are triple-class exposed (TCE), defined as prior exposure to an IMiD, a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb), represent an increasingly large subgroup of RRMM pts. The objective of this study was to describe the incidence and characteristics of SPMs in Medicare-insured pts with TCE RRMM initiating a new line of therapy (LOT). Methods Adult pts with an incident diagnosis (Dx) of MM (≥2 outpatient Dx 30-365 days apart OR ≥1 inpatient Dx AND 6 months of continuous eligibility prior to initial Dx) during the study period (Nov 14, 2006-Dec 31, 2020) who were TCE (≥1 claim each for an IMiD, a PI, and an anti-CD38 mAb) were selected from the Center for Medicare and Medicaid Services Chronic Conditions Data Warehouse (TCE pts were assumed to have RRMM based on exposure). The first LOT after TCE was defined as the index LOT and the associated date of initiation was defined as the index date. Pts with SPMs prior to the index date were excluded. SPMs were identified based on having ≥2 outpatient Dx of SPM (of the same cancer type) 30-365 days apart OR ≥1 inpatient Dx of SPM. Dx of SPM included Dx of invasive malignancies or myelodysplastic syndromes (MDS), excluding MM, Waldenström macroglobulinemia, plasma cell leukemia, non-melanoma skin cancers, or primary bone malignancies that were preceded by a Dx of bone metastases. The incidence of SPM was calculated per 100 person years (PY) of follow-up, considering only the first SPM for each pt. Cumulative incidence of SPM (with death as a competing risk) was also calculated. For pts who experienced SPM, overall survival (OS) and measures of healthcare resource utilization (HRU) and costs (in 2021 USD, on a per patient per month [PPPM] basis) were calculated. Results A total of 3,088 TCE RRMM pts were identified, of whom 989 had no evidence of SPM prior to the index date (Table). These 989 pts had a mean age of 75.2 years, a mean of 2.9 prior LOTs and a mean of 3.1 years since MM Dx. Over a median follow-up of 7.1 months, 166 pts (19.3 per 100 PY) experienced an SPM, including 93 (10.8 per 100 PY) with a solid tumor and 73 (8.5 per 100 PY) with a hematologic malignancy. The latter included 27 (3.1 per 100 PY) with acute myeloid leukemia (AML) and 18 (2.1 per 100 PY) with MDS. The cumulative incidence of SPM (95% confidence interval [CI]) at 12, 24, and 36 months was 15.2% (12.8-17.9%), 19.7% (16.8-22.8%), and 23.8% (20.2-27.6%), respectively (Figure). Median (95% CI) OS from SPM Dx was 7.9 months (5.4-10.9). Kaplan-Meier estimated probability of survival (95% CI) at 12, 24, and 36 months following SPM Dx was 40.3% (31.6-48.9%), 27.6% (18.6-37.4%), and 9.5% (2.1-23.8%), respectively. Mean (95% CI) total costs after SPM were $22,514 ($19,105-$26,404) PPPM. Conclusions The incidence of SPM in Medicare-insured TCE RRMM pts is high. Many SPMs in these pts, such as AML, are life-threatening and may interfere with or prevent MM treatment. Pts with SPMs have poor survival and high HRU and costs. With increasing OS for RRMM pts due to therapeutic advancements, there is a need for effective treatments that are not associated with increased risk of SPMs.

Healthcare Resource Utilization and Economic Burden of Cytokine Release Syndrome and Neurotoxicity in Patients with Relapsed and Refractory Multiple Myeloma (RRMM) Receiving Idecabtagene Vicleucel in Earlier-Line Settings in the KarMMa-3 Clinical Trial

Introduction: Adverse events (AE), such as cytokine release syndrome (CRS) and neurological toxicity (NT), have been associated with chimeric antigen receptor (CAR) T cell therapies. Idecabtagene vicleucel (ide-cel, bb2121), a B-cell maturation antigen-directed CAR T cell therapy, demonstrated deep and durable responses in triple-class exposed (TCE) patients (pts) with RRMM in the pivotal, single-arm, open-label phase 2 KarMMa (3 prior lines of therapy [LOTs]; NCT03361748) (Munshi NC, et al. NEJM 2021;384:705-716) and superior progression-free survival with ide-cel vs standard regimens in the phase 3 KarMMa-3 trial (2-4 prior LOTS; NCT03651128) (Rodríguez-Otero P, et al. NEJM 2023;388:1002-1014). Healthcare resource utilization (HCRU) and costs associated with CRS/NT management were estimated previously for pts receiving ide-cel in the KarMMa trial (McGarvey N, et al. Value Health 2023;26:S89) and suggested low rates of severe (grade ≥ 3) CRS/NT following ide-cel infusion and higher HCRU and costs with increasing AE severity. To further assess resource and economic burden associated with care of treatment-emergent AEs, this analysis evaluated HCRU and estimated cost of CRS/NT management among pts treated with ide-cel in earlier-line settings in the KarMMa-3 study. Methods: In this retrospective study, case report forms from the KarMMa-3 clinical trial database among pts experiencing a CRS and/or NT event that initiated within 90 days post ide-cel infusion were assessed. Pt-level HCRU data, including hospitalizations and length of hospital stay (LOS) (standard inpatient [IP], intensive care unit [ICU] days), diagnostics (eg, lab work, imaging), procedures (eg, dialysis, intubation), and medications (eg, oncology supportive care, prophylactics, other AE management) were identified from CRS/NT onset through resolution. AE management costs were estimated using a micro-costing methodology in which unit costs sourced from public databases or literature (eg, United States Centers for Medicare and Medicaid Services, Healthcare Cost and Utilization Project, IBM ® Micromedex ® RED BOOK ®) were adjusted to 2022 US dollars (USD) using the Consumer Price Index and applied to each HCRU identified. Results: Of 225 pts treated with ide-cel in the KarMMa-3 trial, 203 (90.2%) experienced any grade CRS and/or NT event. Pts experiencing a CRS/NT event had a mean (standard deviation [SD]) age of 61.9 (8.9) years and most were male (123/203 [60.6%]), White (138/203 [68.0%]), and non-Hispanic or Latino (138/203 [68.0%]). The majority (187/203 [92.1%]) of pts experienced less severe CRS/NT events (grade ≤ 2), which resolved quicker and relatively few pts (16/203 [7.9%]) had a more severe (grade ≥ 3) event, which took longer to resolve. Among pts who received ide-cel, the estimated median cost of AE management ranged from USD 17,124 (CRS only grade 1) to USD 181,552 (nonconcurrent CRS or NT grade ≥ 3) (Figure 1). Additional median costs for a pt with a grade ≥ 3 CRS/NT event was USD 31,045 higher than a grade ≤ 2 CRS/NT event. Across AE categories, the main contributors to CRS/NT management were facility costs, namely standard IP hospitalizations and ICU stays. Almost all pts (202/203 [99.5%]) had a standard IP hospitalization; 3.9% (8/203) had an ICU stay (Table 1). The trial protocol required a stay of ≥ 15 days post infusion unless admitted to the ICU; some hospitalization days recorded during the AE overlapped with the protocol-required stay. ICU admissions were more common among pts with CRS/NT grade ≥ 3 (7/16 [43.8%]) than those with grade ≤ 2 (1/187 [0.5%]). Median (range) total LOS was 10 days longer among pts with grade ≥ 3 (14.5 [2-84] days) than those with grade ≤ 2 (4 [1-34] days) CRS/NT. Pts with grade ≥ 3 CRS/NT had higher rates of HCRU than those with grade ≤ 2 for several interventions, such as medications (eg, tocilizumab + corticosteroids: 13/16 [81.3%] vs 63/187 [33.7%]), diagnostics (eg, imaging: 14/16 [87.5%] vs 48/187 [25.7%]), and procedures (eg, dialysis:3/16 [18.8%] vs 0/187 [0%]). Conclusions: Most pts with RRMM treated with ide-cel in the KarMMa-3 trial experienced a CRS and/or NT event, however, few were of high severity (grade ≥ 3). HCRU and costs for CRS/NT increased with AE severity and management. CAR T cell therapies associated with lower-severity AEs and planned interventions to prevent higher-grade AEs may provide an opportunity to better manage HCRU and costs.

Phase I/II Study to Evaluate the Safety, Feasibility, and Efficacy of FP-1201 (Intravenous Interferon-Beta-1a) to Prevent Toxicities after CD19-Directed CAR T-Cell Therapy: Trial in Progress

BACKGROUND CD19 chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of patients with relapsed/refractory B-cell malignancies. Yet it remains limited by potentially life-threatening toxicities such as CRS and ICANS. The risk of CRS and ICANS restricts the use of CD19 CAR T-cell therapy to large academic centers and leads to high healthcare resource utilization. Current toxicity prevention strategies have shown limited efficacy to date (prophylactic steroids with axi-cel: CRS, 80%; ICANS, 60%; Oluwole, BJH, 2021; early intervention with brexu-cel: CRS, 89%; ICANS, 60%; Shah, The Lancet, 2021). Our group has shown that endothelial activation and dysfunction are associated with the development of CRS and ICANS, suggesting a key role of increased vascular permeability and blood-brain barrier damage in their pathogenesis (Hay, Blood, 2017). Type-I interferons (IFN-alpha and beta) are major regulators of CD73 expression by endothelial cells, an enzyme critical to the maintenance of endothelial integrity. CD73 breaks down extracellular pro-inflammatory ATP into anti-inflammatory adenosine. In addition, extracellular ATP has been shown to be a major and early driver of systemic inflammation upstream from IL-6 production (Cauwels, Cell Death Dis, 2014), which is associated with severe CRS and ICANS. Preclinical models have demonstrated that IFN-beta-1a treatment is associated with reduced capillary and blood-brain barrier permeability via upregulation of CD73 expression (Floris, J Neuroimmunol, 2002; Kraus., Ann Neurol, 2004; Niemela, Eur J Immunol, 2008). In humans, two recombinant IFN-beta-1a therapies are FDA-approved for the treatment of multiple sclerosis. IFN-beta-1a given intravenously (IV) maximizes the drug's bioavailability and its protective effects on the endothelium. In a study of patients with ARDS, IV IFN-beta-1a (FP-1201 and FP-1201-lyo) was safe and induced CD73 expression (Bellingan, Lancet Respir Med 2014). Given the known effects of IFN-beta-1a on preserving endothelial function and blood-brain barrier integrity, we hypothesize that IV IFN-beta-1a (FP-1201) may prevent CRS and ICANS following CD19 CAR T-cell therapy ( Figure 1A). Since higher rates of severe CRS and ICANS have been reported after axi-cel and brexu-cel, which contain CD28-costimulatory domains, we will restrict the inclusion criteria to patients treated with these products to analyze a population with a higher unmet need and a more homogeneous risk of CRS/ICANS. STUDY DESIGN AND METHODS Objectives and endpoints: Primary objective: To evaluate the safety and feasibility of FP-1201 in patients undergoing treatment with axi-cel or brexu-cel with two co-primary endpoints: i) to estimate the incidence of dose-limiting toxicity rates within the first 14 days following the last administration of FP-1201; ii) to study the type, frequency, and severity of adverse events according to the NCI CTCAE v5.0 from the first administration of FP-1201 and until day +28 after CAR T-cell infusion Secondary objectives: i) To decrease the incidence and severity of ICANS; ii) to decrease the incidence and severity of CRS; iii) to decrease corticosteroid usage; iv) to evaluate the effect of FP-1201 on anti-tumor efficacy Exploratory objectives: To characterize the in vivo effects of FP-1201 on endothelial function, the systemic cytokine milieu, and CAR T-cell function Key inclusion criteria: Adults ≥18 years of age with Karnofsky performance status ≥60% and B-cell non-Hodgkin lymphoma eligible for treatment with axi-cel or brexu-cel Key exclusion criteria: Known hypersensitivity to IFN-beta or major organ dysfunction FP-1201 administration: The FDA-approved IFN-beta-1a Rebif® will be formulated for IV administration (FP-1201). Participants will receive FP-1201 at one of four dose levels detailed in Figure 1B. Statistical design and sample size: We will use a Bayesian Optimal Interval Design to guide the FP-1201 dose escalation. We will plan to treat up to 24 participants. SUMMARY This is a phase I/II study of IV IFN-beta-1a in preventing CRS and ICANS following axi-cel and brexu-cel. The aim is to demonstrate safety and efficacy and to investigate the biologic mechanisms of IFN-beta-1a in preventing endothelial dysfunction.Additional preclinical and preliminary clinical data will be presented at the meeting. This study is registered on clinicaltrials.gov as NCT05936229.

1743. Health Care Resource Utilisation (HCRU) Due to Respiratory Syncytial Virus (RSV) Before the Age of Two in England

Abstract Background RSV is responsible for 33 million lower respiratory tract infections (LRTI) worldwide. The highest burden occurs in infants &amp;lt; 1 year of age during RSV season, which is from October to February in England. Due to lack of routine laboratory testing, its true disease burden is unknown. This study aimed to estimate the respiratory related primary and secondary care healthcare resource utilisation (HCRU) of RSV admissions before the age two in England. Methods This retrospective cohort study used Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked data to establish a birth cohort of all infants born between 01/03/2015 and 28/02/2017 (n=449,591). Case cohorts included infants under two with a hospital admission of: 1) confirmed RSV (n=4,813), 2) bronchiolitis (n=22,913), 3) any RTI (n=56,871). Each case cohort was compared with all birth cohort infants without the corresponding admission (comparative cohorts). Respiratory related HCRU (primary care, outpatient, accident and emergency [A&amp;E], and inpatient admissions) were estimated in the month prior to and up to 24 months following the first admission in each cohort. Results The RSV-coded cohort had the highest HCRU overall, mean (SD) of 5.1 (4.8) admissions vs. 1.5 (2.4) in its comparative cohort (71% difference). This difference was largely due to A&amp;E and inpatient admissions. Comparable results were found for bronchiolitis-coded and RTI-coded cohorts. The highest rates of inpatient admissions were observed for the RSV-coded case cohort, and these occurred during the calendar months of November and December. Inpatient admissions were largely among infants up to 12 months of age and included infants that were born both before and during the season (Figure 1). Conclusion Infants with an RSV admission had higher HCRU than infants without. Most hospitalisations occurred in November and December when services are at their most stretched. During the first year of life, the HCRU rates observed for infants born before and in the season were equally very high, emphasizing the need for preventative strategies to all infants entering their first RSV season. Funding: This research was funded by collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease. Disclosures Maria João Fonseca, n/a, Sanofi: Advisor/Consultant Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds Richard Hudson, n/a, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds

Medication economic burden of antidepressant non-adherence in Spain.

Introduction: Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs. Methods: A population-based registry study was conducted to assess non-adherence and to analyze the economic burden of treatment and from non-adherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as non-adherent. Results: In 2021, 246,718 patients (10.60% [95% CI: 10.48-10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52-20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest non-adherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine). Conclusion: Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions.

Abstract 17886: Temporal Trends, Healthcare Resource Utilization and In Hospital Outcomes of Infective Endocarditis Following Transcatheter Edge-to-Edge Repair Using Mitraclip Among Elderly Patients With Severe Mitral Regurgitation: A National Perspectives

Introduction: Procedural proficiency combined with the careful selection of patients with severe mitral regurgitation, who are at high or prohibitive risk for cardiac surgery, may have influenced the incidence and outcomes of infective endocarditis (IE) following mitral Transcatheter edge-to-edge repair (TEER). Objective: To assess the temporal trends, healthcare resource utilization (HRU), and in-hospital outcomes of IE post-TEER. Methods: We used the National inpatient sample registry to identify all patients aged &gt; 65 with definite IE post-TEER between 2016 and 2020. Temporal incidence trends, in-hospital mortality, length of stay, and discharge disposition were analyzed. Results: During the study period, there were an estimated 71 cases of endocarditis among patients 65 years and older following mitral TEER, representing 355 discharges (1.0% of TEER-associated discharges) nationally. The temporal trend of the incidence of IE is shown in Figure 1. Relative to its absence, the occurrence of IE following TEER was associated with a 30.3% increased risk of HRU (Patient Average Treatment effect - PATE estimate = 0.303; 95% confidence interval (CI) =0.214 - 0.391; P&lt;0.001); a 13.2% increased risk of AKI (PATE estimate = 0.132; 95% confidence interval (CI) =0.033 - 0.232; p=0.009) and a 6.2% increased risk of in-hospital mortality (PATE estimate = 0.062; 95% confidence interval (CI) =0.008 - 0.117; p=0.025) Conclusions: Among elderly patients with severe symptomatic mitral regurgitation, who are at high or prohibitive risk for cardiac surgery, the incidence of TEER-associated IE appears to be trending downwards. The occurrence of TEER-associated IE confers small but significant high HRU, complication rates, including AKI and in-hospital mortality, compared to those without IE. High-fidelity studies are needed to elucidate these findings.

Symposium 4

Interstitial lung disease (ILD) is a fibrotic disease of the lung parenchyma. It can occur in different connective tissue diseases, including rheumatoid arthritis (RA). Smoking, male gender and longstanding RA are possible risk factors for developing ILD 1 . Being a common extra-articular manifestation of RA, it can contribute to decreased quality of life, chronic disability, high utilization of healthcare resources, and may also lead to substantial morbidity and mortality for affected patients1. Hence, early identification and management is of paramount importance to improve patient outcomes. Clinical presentation, chest X-ray, pulmonary function testing and high-resolution computed tomography are common tools for investigation and they also allows assessment of subtype and disease extent 2 . The histopathologic and radiographic features of RA-ILD are heterogeneous. The most frequent patterns of RA-ILD are usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). Distinguishing the patterns is useful in predicting prognosis and would also affect subsequent management approach 2 . Traditionally treatment initiated for RA-ILD was generally empirical. Corticosteroids were often used as first-line agents and immunosuppressants maybe added2. However, these treatments are not specific and mainly target inflammation instead of fibrosis. With the advance in medicine, antifibrotic is now indicated for treating fibrosing ILD with progressive phenotype. FVC decline can be slowed in patients with connective tissue disease associated progressive ILD 3 . In this lecture, Prof. Vanessa Smith will share the current knowledge and evidence in RA-ILD. The approach on identifying and screening ILD in RA patients would be presented. The management strategy and options would also be reviewed.