Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States.

BACKGROUND: Incidence and risk factors for seizures among women with advanced breast cancer (BC) and brain metastases are not well characterized across treatment-related or clinical subtypes. This study leveraged a large real-world dataset to describe incidence and risk factors for seizures in BRCA-associated metastatic breast cancer. METHODS: The Optum® de-identified electronic health records database was used. Females with a BC diagnoses between 2008 and 2018, with clinic visits 12 months before BC index date, evidence of BRCA mutation (BRCA+), evidence of metastasis, and no previous cancers were included. Analyses were stratified by the overall BRCA+ cohort and 4 molecular phenotypes: HER2+/HR- (human epidermal growth factor 2/hormone receptor), HER2-/HR+, HER2+/HR+, and triple negative BC (TNBC; HER2-/HR-). Seizures were identified using diagnosis codes and natural language processing. Incidence, occurrence rates, and cumulative incidence of seizures from the diagnosis of metastasis to the end of follow up were calculated. Comparisons were made between phenotypes and stratified on PARP inhibitor use, diagnosed brain metastases, history of seizures, and anticonvulsants use before BC. All comparisons included age at metastasis, number of prior lines of treatment, and metastasis location as covariates. RESULTS: 27.8% of 7941 BRCA+ patients had ≥1 seizure over a mean follow-up time of 2.35 years. Incidence and occurrence rates were 11.83 (95% CI: 11.35-12.33) and 201.3 (95% CI: 198.05-204.50), respectively, per 100 person-years. HER2-/HR+ and TNBC patients had the lowest and highest seizure incidence rates, respectively (10.94 [95% CI: 10.23-11.71] and 16.83 [95% CI: 15.34-18.46]). With HER2-/HR+ as the reference group in a competing risk analysis, TNBC (hazard ratio, HR = 1.35; 95%CI: 1.21, 1.52; p < 0.001) and HER2+/HR- (HR = 1.29; 95%CI: 1.07, 1.56; p < 0.01) patients had a greater risk of seizures. Patients with diagnosed brain metastases or a history of seizures had higher seizure rates. Incidence trended higher with PARP inhibitor use, but patient numbers were low. CONCLUSIONS: This study provides novel real-world evidence on seizure incidence rates in BRCA+ BC patients, even those without diagnosed brain metastases, and underscores the need to understand patients' tumor phenotypes when assessing seizure risk. These findings may have implications for clinical practice and assessment of benefit-risk ratios of new therapeutic agents.

Venetoclax plus azacitidine compared with intensive chemotherapy as induction for patients with acute myeloid leukemia: retrospective analysis of an electronic medical record database in the United States.

Intensive chemotherapy (IC) is commonly used to achieve remission in patients with acute myeloid leukemia (AML). Venetoclax plus azacitidine (VEN-AZA) is FDA-approved to treat patients with AML aged ≥ 75 years or who are ineligible for IC. This retrospective analysis used de-identified electronic health records from the US-based Flatiron Health database from patients diagnosed 11/21/2018 to 10/31/2021 to compare treatment outcomes with VEN-AZA vs. IC. Patients were 1:1 propensity score-matched ([Formula: see text]). Assessments included rates of complete remission (CR) and hematopoietic stem cell transplant (HSCT), overall survival (OS), and relapse-free survival (RFS). CR and HSCT rates were higher with IC than with VEN-AZA (60.9% vs. 44.2% [P = 0.006] and 18.1% vs. 8.0% [P = 0.012], respectively). Median OS was 17.7 months in patients treated with IC and 11.3 months with VEN-AZA without censoring (P = 0.278) and 13.7 vs. 10.6 months, respectively, with censoring at HSCT (P = 0.584). Median RFS was 12.0 months in patients treated with IC vs. 9.5 months with VEN-AZA without censoring (P = 0.431) and 6.4 vs. 7.4 months, respectively, with censoring at HSCT (P = 0.444). No OS or RFS differences observed between the two arms reached statistical significance. Randomized controlled trials comparing the two approaches are warranted, as are novel approaches to reduce relapse rates following CR.

A US real-world study of treatment patterns and outcomes in localized or locally advanced prostate cancer patients.

PURPOSE: Men with localized or locally advanced prostate cancer (LPC/LAPC) are at risk of progression after radiotherapy (RT) or radical prostatectomy (RP). Using real-world data, we evaluated patient characteristics, treatment patterns, and outcomes in LPC/LAPC. METHODS: Optum claims and electronic health records (EHR) data from January 2010 to December 2021 were queried for men with LPC/LAPC who received primary RT, RP, or androgen deprivation therapy alone within 180 days after diagnosis. Survival outcomes were analyzed using descriptive statistics and Kaplan-Meier curves. Real-world overall survival (rwOS) was compared in patients with and without evidence of disease (i.e., disease recurrence, metastasis, diagnosis of castration-resistant PC) at defined time points. RESULTS: 61,772 and 62,361 men in claims and EHR cohorts met the inclusion criteria. Median follow-up was 719 and 901 days, respectively. Most men received primary RT (51.0% claims, 35.0% EHR) or RP (39.4% claims, 53.8% EHR). Survival was greatest among men treated with RP, followed by RT. Adjusted for age and comorbidity, rwOS was shorter among men with evidence of disease within 1, 3, 4, and 5 years after primary treatment than those without at the same time points. CONCLUSION: Real-world claims and EHR data show that survival among men with LPC/LAPC differs by primary treatment and time point of disease recurrence thereafter. Poor outcomes in men with LPC/LAPC who progress early indicate an unmet medical need for more effective primary treatment. If validated for surrogacy, no evidence of disease at specific time points could represent an intermediate efficacy endpoint in future trials.

Work loss and activity impairment due to extended nausea and vomiting in patients with breast cancer receiving CINV prophylaxis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.

Model-based evaluation of the impact of prophylactic vaccination applied to Ebola epidemics in Sierra Leone and Democratic Republic of Congo.

BACKGROUND: Protection by preventive Ebola vaccines has been demonstrated in clinical trials, but a complete picture of real-world effectiveness is lacking. Our previous study modeling the impact of preventively vaccinating healthcare workers (HCW) alone or with a proportion of the general population (GP) estimated significant reductions in incidence and mortality. The model assumed 100% vaccine efficacy, which is unlikely in the real world. We enhanced this model to account for lower vaccine efficacy and to factor in reduced infectiousness and lower case fatality rate in vaccinated individuals with breakthrough infections. METHODS: The previous model was enhanced to still permit a risk, although lower, for vaccinated individuals to become infected. The enhanced model, calibrated with data from epidemics in Sierra Leone (SL) and North Kivu, Democratic Republic of the Congo, helped evaluate the impact of preventive Ebola vaccination in different scenarios based on different vaccine efficacy rates (90% and 30% reductions in infection risk in the base and conservative scenarios, respectively; additionally, both scenarios with 50% reductions in infectiousness and mortality) and vaccination coverage among HCWs (30%, 90%) and GP (0%, 5%, and 10%). RESULTS: The base scenario estimated that, depending upon the proportions of vaccinated HCWs and GP, 33-85% of cases and 34-87% of deaths during the 2014 SL epidemic and 42-89% of cases and 41-89% of deaths during the 2018 North Kivu epidemic would be averted versus no vaccination. Corresponding estimates for the conservative scenario were: 23-74% of cases and 23-77% of deaths averted during the SL epidemic and 31-80% of both cases and deaths averted during the North Kivu epidemic. CONCLUSIONS: Preventive vaccination targeting HCW alone or with GP may significantly reduce the size and mortality of an EVD outbreak, even with modest efficacy and coverage. Vaccines may also confer additional benefits through reduced infectiousness and mortality in breakthrough cases.

Avoidable Acute Care Use Associated with Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) contributes to avoidable acute care, a metric now tracked in Medicare's oncology outcome measure. CINV is preventable, yet guidelines are often not followed. We sought to quantify acute care involving CINV and other avoidable toxicities after highly emetogenic chemotherapy (HEC) to identify excess risk and assess clinician adherence to antiemesis guidelines for HEC. MATERIALS AND METHODS: We retrospectively evaluated U.S. electronic health records (2012-2018) using Medicare's OP-35 outcome measure to identify avoidable acute care involving any of 10 toxicities, including CINV, after HEC regimens relative to non-HEC. Antiemetic guideline adherence was defined as use ofneurokinin-1 (NKl) receptor antagonists Q5 (RAs) plus 5-hydroxytryptamine type 3 RA+ dexamethasone at HEC initiation. RESULTS: Among 17,609 patients receiving HEC, acute care rates associated with HEC chemotherapy included 32% cisplatin, 31% carboplatin, and 21% anthracycline/cyclosphospharnide (AC), with 76% meeting the criteria as avoidable events. Oxaliplatin rates were 29%. Avoidable acute care occurred 1.83 times (95% confidence interval, 1.76-1.91, p < .0001) as often after HEC versus non-HEC excluding oxaliplatin; CINV-related acute care occurred 2.29 times as often. Nonadherence to antiemesis guidelines occurred in 34% and 24% of cisplatin and AC courses, respectively, because of omission of a NKl RA. CONCLUSIONS: Patients treated with HEC regimens experienced high avoidable acute care use, 1.8 times the risk seen for other chemotherapy. Nonadherence to guideline-directed antiemetic prophylaxis highlights the need to ensure adherence to antiemetic guidelines, including the use of NKl RA in HEC. IMPLICATIONS FOR PRACTICE: After survival, perhaps the most important goal in oncology is limiting avoidable acute care, a goal now used by Medicare to impact cancer reimbursement. This study found that patients treated with highly emetogenic chemotherapy (HEC) regimens had high rates of avoidable acute care use, 1.8 times the risk seen for other chemotherapy. A substantial proportion of the avoidable acute care involved chemotherapy-induced nausea and vomiting. Results showed that incomplete adherence to national antiemetic guidelines for HEC regimens primarily driven by omission of upfront neurokinin-1 receptor antagonist use, suggesting that improved adherence can meaningfully resolve this gap in quality and cost of care.

Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma.

BACKGROUND: For patients with multiple myeloma (MM), each additional line of therapy (LOT) is associated with lower response rates, shorter treatment duration and treatment-free intervals, and increased rates of toxicities and comorbidities. Here, we examine frontline treatment patterns, and attrition rates by LOT among newly diagnosed MM (NDMM) patients in the United States who were eligible or ineligible for autologous stem cell transplant (ASCT). METHODS: Data were identified from three US patient-level databases collectively covering the period January 2000 to September 2018. Patients had an index diagnosis of MM on or after January 1, 2007, medical and prescription insurance coverage at diagnosis, a 1-year look-back period prior to the index diagnosis, no prior malignancies in the 1-year period before index diagnosis, and had received ≥1 LOT. RESULTS: Among patients who did not receive ASCT (non-transplant; n = 22,062), 12,557 (57%) received only 1 LOT and 9505 (43%) received > 1 LOT. Patients receiving only 1 LOT were significantly older, had higher mean Charlson Comorbidity Index (CCI) scores, and higher incidences of comorbidities. Among the 2763 patients receiving ASCT, 2184 received > 1 LOT, and 579 (21%) received only 1 LOT (ie, ASCT was the last treatment). 1682 (61%) patients received induction therapy as frontline treatment, of whom 187 (11%) also received consolidation therapy. The latter group was younger than those who received only induction therapy, had lower mean CCI scores, and comparable or lower incidences of selected comorbidities. The most common frontline therapy for non-transplant and transplant-eligible patients was bortezomib/dexamethasone and bortezomib/lenalidomide/dexamethasone, respectively. Attrition rates across all LOTs were high for non-transplant patients (range, 43-57%) and transplant patients (range, 21-37%). Treatment duration decreased by LOT for non-transplant patients and was consistent across LOTs for transplant patients. CONCLUSIONS: In this analysis, a substantial proportion of patients with NDMM who received frontline therapy did not appear to receive a subsequent LOT. These high attrition rates underscore the need to use the most optimal treatment regimens upfront rather than reserving them for later LOTs in which the clinical benefit may decrease.

What the HEC? Clinician Adherence to Evidence-Based Antiemetic Prophylaxis for Highly Emetogenic Chemotherapy.

BACKGROUND: Clinician adherence to antiemetic guidelines for preventing chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC) remains poorly characterized. The primary aim of this study was to evaluate individual clinician adherence to HEC antiemetic guidelines. PATIENTS AND METHODS: A retrospective analysis of patients receiving HEC was conducted using the IBM Watson Explorys Electronic Health Record Database (2012-2018). HEC antiemetic guideline adherence was defined as prescription of triple prophylaxis (neurokinin-1 receptor antagonist [NK1 RA], serotonin type-3 receptor antagonist, dexamethasone) at initiation of cisplatin or anthracycline + cyclophosphamide (AC). Clinicians who prescribed ≥5 HEC courses were included and individual guideline adherence was assessed, noting the number of prescribing clinicians with >90% adherence. RESULTS: A total of 217 clinicians were identified who prescribed 2,543 cisplatin and 1,490 AC courses. Patients (N=4,033) were primarily women (63.3%) and chemotherapy-naïve (92%) with a mean age of 58.6 years. Breast (36%) and thoracic (19%) cancers were the most common tumor types. Guideline adherence rates of >90% were achieved by 35% and 58% of clinicians using cisplatin or AC, respectively. Omission of an NK1 RA was the most common practice of nonadherence. Variation in prophylaxis guideline adherence was considerable for cisplatin (mean, 71%; SD, 29%; coefficient of variation [CV], 0.40) and AC (mean, 84%; SD, 26%; CV, 0.31). CONCLUSIONS: Findings showed substantial gaps in clinician adherence to HEC CINV guidelines, including a high variability across clinicians. Clinicians should review their individual clinical practices and ensure adherence to evidence-based CINV guidelines to optimize patient care.

Long-term impact of the adoption of bedaquiline-containing regimens on the burden of drug-resistant tuberculosis in China.

BACKGROUND: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China. METHODS: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment. RESULTS: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption. CONCLUSIONS: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.

Analysis of Real-World Data on Overall Survival in Multiple Myeloma Patients With ≥3 Prior Lines of Therapy Including a Proteasome Inhibitor (PI) and an Immunomodulatory Drug (IMiD), or Double Refractory to a PI and an IMiD.

BACKGROUND: This retrospective study evaluated the treatment patterns in and overall survival (OS) of multiple myeloma (MM) patients who were refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) or who had received three or more prior lines of therapy (LOTs) including a PI and an IMiD. METHODS: Electronic health records in the IMS LifeLink and OPTUM databases were screened for indexing periods of 2000-2014 and 2007-2014, respectively. Patients who were refractory to both a PI and an IMiD (criterion 1) or who received three or more prior LOTs (including a PI and an IMiD) and showed disease progression within 60 days of their most recent regimen (criterion 2) comprised the eligible population. Median OS from time of last LOT was assessed for the full cohort, cohorts meeting criteria 1 and 2, and clinically important subgroups. RESULTS: Of 3,929 and 3,837 patients with MM diagnoses evaluated in the IMS LifeLink and OPTUM databases, 500 and 162 met the eligibility criteria, respectively. Similar median OS was observed for eligible patients in the IMS LifeLink and OPTUM databases (7.9 vs. 7.9 months; p = .5358). In subgroup analyses of the IMS LifeLink data set, median OS was longer in patients <65 years of age than it was for those ≥65 years at eligibility (9.5 vs 6.7 months; p < .01) and in patients with good or unreported versus poor performance status at last claim (7.8 or 8.8 vs. 2.9 months; p < .0001). CONCLUSION: The findings of this survival analysis suggest that outcomes for these patients remain poor despite the availability of newer agents. IMPLICATIONS FOR PRACTICE: This real-world retrospective study of electronic health records examines the survival outcomes of patients with multiple myeloma who are heavily pretreated or highly refractory to currently approved treatments, including recently approved proteasome inhibitors and immunomodulatory drugs. This survival analysis showed that outcomes for these patients remain poor despite the availability of newer agents, with median overall survival of approximately 8 months. These findings highlight a critical need to develop novel therapies for these patients and also serve as a reference point against which emerging agents for heavily pretreated or highly refractory disease may be evaluated.

Differences in Healthcare Resource Use and Cost by Pharmacotherapy Among Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: Real-World Analysis of Claims Data.

BACKGROUND: For symptomatic obstructive hypertrophic cardiomyopathy (oHCM), limited evidence exists on healthcare resource utilization (HRU) and cost for patients with symptomatic oHCM by treatment categories. We evaluated whether HRU and costs vary by initial treatment in symptomatic oHCM. METHODS: This is a retrospective study of medical and pharmacy claims from 2016 to 2021 to identify (per International Classification of Disease Tenth Revision diagnosis codes) adult patients in the USA with symptomatic oHCM. Patients included in the study cohort were required to be treatment naïve (≥ 12 months' activity before first treatment) and symptomatic (fatigue, chest pain, syncope, dyspnea, heart failure, or palpitations within 3 months of index date). Patients were grouped by first index treatment [beta blocker (BB), calcium channel blockers (CCB), disopyramide, combination therapy], and HRU and costs [per person per year (PPPY), in USD] by initial treatment were reported. RESULTS: Among 7334 patients with symptomatic oHCM, initial treatment included BB (65.8%), CCB (21.1%), disopyramide (1.2%), or BB + CCB (11.9%). Overall, 87.2% were prescribed monotherapy. Outpatient visits were the main driver of all-cause HRU (mean 11.5 PPPY), and varied by initial treatment (BB: 11.0, CCB: 10.5, disopyramide: 7.2, combination therapy: 12.1). All-cause urgent care visits were more frequent than inpatient visits (means: 5.4 and 0.83 PPPY, respectively). All-cause incurred costs were $46,628 PPPY overall and varied by treatment (BB: $47,029, CCB: $42,124, disopyramide: $27,007, combination therapy: $54,024). CONCLUSIONS: In this large, US-based cohort of patients with symptomatic oHCM, initial therapy was most commonly BB and CCB monotherapy. Costs and HRU were high for most patients, but greater for those treated initially with combination therapy.

Adherence, Persistence, Healthcare Resource Use, and Costs in Tofacitinib-Treated Patients with Psoriatic Arthritis: Data from Two United States Claims Databases.

INTRODUCTION: Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs were reported in patients with psoriatic arthritis (PsA). We assessed characteristics/outcomes of patients with PsA receiving tofacitinib monotherapy vs combination therapy with conventional synthetic disease-modifying antirheumatic drugs. METHODS: Claims data from Optum® Clinformatics® Data Mart (OC) and Merative™ MarketScan® (MS) databases between December 2017 and February 2020 were analyzed. Outcomes assessed were adherence/persistence by therapy type (monotherapy/combination therapy); HCRU/costs (per patient per month) by periods on-treatment (sum time on tofacitinib) and off-treatment (sum time off tofacitinib [gap of > 60 days]) plus therapy type. RESULTS: This analysis included 274 and 395 tofacitinib-treated patients in OC (70.4% female, mean age 54.4 years) and MS (68.9% female, mean age 51.4 years), respectively. Percentages of patients with a proportion of days covered ≥ 0.8 at 12 months for monotherapy vs combination therapy were OC, 44.5% vs 53.8%; MS, 36.4% vs 45.7%. Generally similar trends were seen over 24 months and for medication possession ratio ≥ 0.8. Median (95% confidence interval) times to treatment discontinuation for monotherapy vs combination therapy were OC, 10.1 (7.4-11.8) vs 16.7 (8.3-26.6) months; MS, 6.9 (5.6-9.4) vs 11.0 (6.1-13.9) months. During off-treatment vs on-treatment periods, numerical decreases were observed for all-cause (OC, $5383 vs $6149; MS, $4145 vs $5180) and PsA-related costs (OC, $3237 vs $4515; MS, $2703 vs $3907) regardless of therapy type. During off-treatment vs on-treatment periods, numerical increases in outpatient visits for all-cause (OC, 2.37 vs 2.05; MS, 2.15 vs 1.99) and PsA-related visits (OC, 0.60 vs 0.46; MS, 0.47 vs 0.44) were observed, and PsA-related medications numerically decreased (OC, 1.21 vs 1.53; MS, 1.05 vs 1.48). CONCLUSION: In this USA-based claims analysis, tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased off-treatment vs on-treatment, irrespective of therapy type, driven by lower medication costs.

Healthcare Utilization and Costs Among Patients with Acute Myeloid Leukemia Receiving Oral Azacitidine Maintenance Therapy Versus No Maintenance: A US Claims Database Study.

INTRODUCTION: The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA. METHODS: Data from IQVIA PharMetrics® Plus (January 1, 2016-June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance ("watch and wait" [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs. RESULTS: After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months-NR] vs 3.3 months [0.8 months-NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001). CONCLUSIONS: Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice.

Comparative evaluation of costs and healthcare resource utilization of oral selexipag versus inhaled treprostinil or oral treprostinil in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH), a rare vasculopathy progressively leading to right heart failure and death, is associated with considerable economic burden. Oral prostacyclin pathway agents (PPAs) like selexipag and treprostinil address an underlying PAH pathway, yet are often under-utilized. Data on head-to-head cost comparison of various PPAs is lacking. METHODS: In this retrospective study using a large health claims database, we compared the per-patient-per-year (PPPY) costs and healthcare resource utilization (HRU) among PAH patients taking either oral selexipag, inhaled treprostinil or oral treprostinil in the United States between July 2015 and March 2020. Patients with ≥1 prescription for one of the drugs of interest, ≥1 in-patient pulmonary hypertension (PH) diagnosis, or ≥ 2 outpatient PH diagnoses were included in this study. Baseline differences between the three groups were adjusted using an inverse probability of treatment weighting approach. 411 patients were selected for the final study cohorts. RESULTS: All-cause hospitalization costs were highest for oral treprostinil ($39,983) compared to oral selexipag ($20,635) and inhaled treprostinil ($16,548; p = .037). Total PAH-related medical costs were 40% lower for patients on oral selexipag compared to patients on oral and inhaled treprostinil ($24,351 vs. $40,398 and $40,339, respectively; p = .006). PAH-related outpatient visits were lowest for patients on oral selexipag (14 PPPY visits) compared to oral treprostinil (16 PPPY visits) and inhaled treprostinil (22 PPPY visits; p = .001). CONCLUSIONS: Compared to oral and inhaled treprostinil, oral selexipag may incur lower medical costs and reduce PAH related outpatient visits for patients with PAH.

Correlation between pathologic complete response, event-free survival/disease-free survival and overall survival in neoadjuvant and/or adjuvant HR+/HER2-breast cancer.

Purpose: The study's purpose was to evaluate the correlation between overall survival (OS) and its potential surrogate endpoints: pathologic complete response (pCR) and event-free survival (EFS)/disease-free survival (DFS) in neoadjuvant and/or adjuvant HR+/HER2- breast cancer. Methods: Systematic search was performed in MEDLINE, EMBASE, Cochrane Library databases and other relevant sources to identify literature that have reported outcomes of interest in the target setting. The strength of correlation of EFS/DFS with OS, pCR with OS, and pCR with EFS/DFS was measured using Pearson's correlation coefficient (r) based on weighted regression analysis. For Surrogate Endpoint-True Endpoint pairs where correlation was found to be moderate, surrogate threshold effect (STE) was estimated using a mixed-effects model. Sensitivity analyses were conducted on the scale and weights used and removing outlier data. Results: Moderate correlation was observed of relative measures [log(HR)] of EFS/DFS and OS (r = 0.91; 95% CI: 0.83, 0.96, p < 0.0001). STE for HREFS/DFS was estimated to be 0.73. Association between EFS/DFS at 1, 2 and 3 years with OS at 4- and 5-year landmarks was moderate. Relative treatment effects of pCR and EFS/DFS were not strongly associated (r: 0.24; 95% CI: -0.63, 0.84, p = 0.6028). Correlation between pCR and OS was either not evaluated due to inadequate sample size (relative outcomes) or weak (absolute outcomes). Results obtained in the sensitivity analyses were similar to base scenario. Conclusion: EFS/DFS were moderately correlated with OS in this trial-level analysis. They may be considered as valid surrogates for OS in HR+/HER2- breast cancer.

The Impact of Outpatient versus Inpatient Administration of CAR-T Therapies on Clinical, Economic, and Humanistic Outcomes in Patients with Hematological Cancer: A Systematic Literature Review.

Although chimeric antigen receptor (CAR)-T cell therapies are typically administered in the inpatient setting, outpatient administration is rapidly expanding. However, there is limited summarized evidence comparing outcomes between outpatient and inpatient administration. This systematic literature review aims to compare the safety, efficacy, quality of life (QoL), costs, and healthcare resource utilization (HCRU) outcomes in patients with hematological cancer who are administered CAR-T therapy in an outpatient versus an inpatient setting. Publications (2016 or later) that reported the outcomes of interest in patients treated with a CAR-T therapy in both outpatient and inpatient settings, or only the outpatient setting, were reviewed. In total, 38 publications based on 21 studies were included. Safety findings suggested the comparable frequency of adverse events in the two settings. Eleven studies that reported data in both settings showed comparable response rates (80-82% in outpatient and 72-80% in inpatient). Improvements in the QoL were observed in both settings while costs associated with CAR-T therapy were lower in the outpatient setting. Although unplanned hospitalizations were higher in the outpatient cohort, overall HCRU was lower. Outpatient administration of CAR-T therapy appears to have comparable outcomes in safety, efficacy, and QoL to inpatient administration while reducing the economic burden.

Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases.

BACKGROUND: This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis. METHODS: Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method. RESULTS: About 1347 patients (EHR, n = 776; claims, n = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were $19,343 and $105,944 for LOT1, $19,183 and $95,793 for LOT2, and $16,611 and $128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively. CONCLUSION: AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden.

Real-world analysis of insurance churn among young adults with schizophrenia using the Colorado All-Payer Claims Database.

BACKGROUND: Most patients with schizophrenia are diagnosed in their early twenties and often have commercial insurance at diagnosis. These young adults can experience changes in insurance coverage, that is, "churn," which can lead to disruptions in care. OBJECTIVE: To examine the frequency, speed, and type of insurance churn events in a young adult schizophrenia population with commercial insurance coverage at diagnosis. METHODS: The Colorado All-Payer Claims Database, containing insurance claims data from commercial and public insurers for Colorado residents, was used for the study. Eligible patients were required to have at least 1 inpatient or 2 outpatient claims for schizophrenia or schizoaffective disorder, be of age 18-34 years at index, have previous insurance coverage for 12 consecutive months, and have commercial insurance at diagnosis. These patients were 1:5 propensity score matched (PSM) with nonschizophrenia members. Percentages of members on different insurance types were calculated monthly to assess churn events. Cohorts were compared using descriptive statistics, Cox proportional hazards, and generalized estimating equation models. RESULTS: The matched schizophrenia and nonschizophrenia cohorts comprised 501 and 2,510 members, respectively. Before PSM, cohorts were imbalanced (schizophrenia cohort had a younger median age and higher proportion of males). After matching, the cohorts were similar in terms of the matched baseline characteristics. Previous mental health disorders were more common in the schizophrenia cohort (75%) than in the nonschizophrenia cohort (26%). The proportion of members with at least 1 churn event for the schizophrenia and nonschizophrenia cohorts, respectively, were 53.8% vs 36.5% after 12 months and 84.6% vs 69.2% after 48 months. Time to first churn event was significantly shorter in the schizophrenia cohort (16 months) than the nonschizophrenia cohort (23 months; P < 0.001). Schizophrenia cohort members had 64.1 and 56.8 churn events per 1,000 members per month vs 43.0 (P ≤ 0.001) and 42.8 (P = 0.011) churn events for nonschizophrenia cohort members in the first and second 6-month periods, respectively. Proportions of members in the schizophrenia and nonschizophrenia cohorts on public insurance, respectively, were 22.9% vs 6.9% after 12 months and 52.4% and 10.7% after 48 months. In the schizophrenia cohort, the most common churn event type was from commercial to public insurance rather than to a different commercial insurance; notably, 41% of members were still on a commercial plan 4 years after diagnosis. CONCLUSIONS: Young adults with schizophrenia experienced churn events more rapidly and more frequently than those without schizophrenia for the first 4 years studied after the index date. These disruptions may be associated with reduced access to care and treatment gaps in this vulnerable patient population. DISCLOSURES: This research was sponsored by Janssen Scientific Affairs, LLC. Pesa, Benson, and Patel are employees of Janssen Scientific Affairs, LLC, and are stockholders of Johnson & Johnson. Potluri, Rotter, and Papademetriou are employees of SmartAnalyst Inc, and their work on this study was funded by Janssen Pharmaceuticals. A version of this study was presented as a poster at the Psych Congress 2020 Virtual Experience, September 10-13, 2020.

Study on stereoacuity and associated factors in school children aged 7 to 14 years.

PURPOSE: The study aimed to estimate the prevalence of subnormal stereoacuity in school children and to assess the factors associated with it. METHODS: In this prospective cross-sectional study, a total of 2,376 school children without amblyopia and manifest squint were screened by the titmus fly test, Snellen chart, tests for heterophoria, anterior segment examination, and fundoscopy. Children with a manifest squint, amblyopia (best-corrected visual acuity [BCVA] <6/18), and history of ocular trauma or surgery, and one-eyed children were excluded. Cycloplegic refraction was done in children with uncorrected or undercorrected refractive errors, and stereoacuity was assessed again with spectacle correction. RESULTS: The prevalence of normal stereoacuity by titmus fly test was 93.18% with correction of refractive errors. Girls had slightly better stereopsis compared with boys. The subnormal stereoacuity was significantly associated with refractive error (P < 0.00001, significant at P < 0.05), unilateral refractive error (P < 0.00001, significant at P < 0.05), bilateral refractive error (P < 0.00001, significant at P < 0.05), anisometropia (P < 0.00001, significant at P < 0.05), ametropia (P < 0.00001, significant at P < 0.05), lower BCVA (P < 0.00001, significant at P < 0.05), hyperopia (P < 0.05, significant at P < 0.05), and heterophoria (P = 0.014, significant at P < 0.05). The subnormal stereoacuity was positively correlated with the magnitude of refractive error of the eyes. CONCLUSION: This study underlines the significant impact of identification and correction of refractive errors and squints in school children. The measurement of stereoacuity will be of immense importance and must be included in the screening programs for children.