Per Patient Per Month Research Articles

Real-world clinical and economic outcomes from rapid start antiretroviral therapy in HIV: systematic review and meta-analysis.

We aimed to synthesize clinical and economic outcomes of rapid start versus non-rapid antiretroviral therapy (ART) in people with HIV (PWH) in real-world settings. A search was conducted in PubMed, Embase, Web of Science, and ProQuest from January 2017 to January 2023, supplementing a previous search by Ford et.al, 2018. Observational studies investigating clinical or economic outcomes of rapid start ART versus non-rapid ART in PWH were included. Clinical outcomes were mortality, loss-to-follow-up (LTFU), and viral suppression. Economic outcomes were Incremental cost-effectiveness ratio (ICER) values and per patient per month (PPPM) costs. Meta-analyses using random-effects models were performed for clinical outcomes, while qualitative syntheses were conducted for economic outcomes. The quality of clinical and economic studies was assessed. Sixty-two studies were included. The pooled adjusted risk ratio (aRR) for mortality demonstrated a significant reduction in risk of mortality among participants who received rapid start ART compared to non-rapid ART (0.80, 95%CI, 0.65-0.98). For LTFU at 6 and 12 months, the pooled aRR showed increased LTFU for rapid start ART (1.33, 95%CI, 1.15-1.55 and 1.18, 95%CI, 0.74-1.89 respectively). All cost-effectiveness studies reported cost-saving or cost-effective findings. The PPPM costs of rapid start ART across the first 36 months of treatment were consistently lower than non-rapid ART. Rapid ART is associated with reduced mortality and is cost-effective compared to non-rapid ART in real-world settings. Clinicians and policymakers should consider these findings to facilitate rapid start of ART in PWH. Further research on LTFU in PWH is needed.

Economic Burden Associated with Pulmonary Arterial Hypertension in the United States.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pressure in the pulmonary arteries, commonly resulting in right heart failure. PAH is associated with a high economic burden throughout the duration of the disease. This retrospective cohort study of the Milliman Contributor Health Source Data, the Medicare 100% Research Identifiable Files, and the Merative Marketscan® Commercial dataset between 2018 and 2020 identified adult patients with prevalent PAH based on the earliest qualifying diagnosis date or medication date ('index date') between January 1, 2019 and November 30, 2020. Outcomes were assessed using patient data from index date through the earliest of end of enrollment, end of data, or death (Medicare fee-for-service [FFS] only). All-cause and PAH-related medical and pharmacy costs per-patient per-month (PPPM) and healthcare resource utilization per 1000 patients were summarized. The study included 11,670 Medicare FFS, 1021 Medicare Advantage, 274 Medicaid, and 1174 commercially insured patients in the US. The annual national burden to payers was estimated to be US$3.1 billion. The PPPM payer costs ranged from US$6500 to US$14,742; out-of-pocket (OOP) costs ranged from US$341 to US$907 PPPM. Inpatient utilization rate ranged from 435 to 770 per 1000 patients for all-cause admissions and from 15 to 58 per 1000 patients for PAH-related admissions. This study demonstrates that PAH continues to be associated with a high economic burden and healthcare resource utilization across all payer types within the US healthcare system.

The economic burden of recurrence in elderly patients with completely resected, stage IIB/IIC or III melanoma: an analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database

Aims To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. Methods Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. Results After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). Limitations Melanoma recurrence was identified using a claims-based algorithm. Conclusions Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence.

Real-world analysis of neuroendocrine tumor misdiagnosis and associated costs

PurposeConditions for which neuroendocrine tumor (NET) is commonly misdiagnosed were compared among patients with and without NET, and the associated healthcare costs were described. MethodsAdults with a NET diagnosis were selected retrospectively from the IBM MarketScan claims databases during 1/1/2015-12/31/2018 (earliest = index), comprising the NET cases. Non-NET controls included age/gender matched patients without any cancer diagnoses. Patients were followed for a five year look back period when conditions for which NET is commonly misdiagnosed (gastrointestinal, respiratory, metabolic [i.e. liver disease], dermatologic) were measured and compared between cases and matched controls using odds ratios. Misdiagnosis-related costs were reported per patient per month (PPPM) from the earliest misdiagnosis to NET diagnosis. Patients with pancreatic adenocarcinoma misdiagnoses and related costs were reported separately. ResultsThis analysis included 3,460 NET cases and 10,370 non-NET controls (mean age 61 years). Compared to non-NET controls, 70% of NET cases had a diagnosis of a gastrointestinal, respiratory, metabolic, or dermatologic condition, with 2.07 higher odds (95% CI 1.91-2.25). Median time from earliest potential misdiagnosis to NET was 3.4 years. Overall mean (standard deviation) healthcare costs related to misdiagnoses were $2,858 ($6,495) PPPM. Costs were highest for gastrointestinal misdiagnoses ($3,350 [$7,108]). Among NET cases, 69 (2%) patients had a pancreatic adenocarcinoma misdiagnosis; related PPPM costs were substantial ($29,321 [$62,385]) and driven by outpatient services including treatment administration. ConclusionThe increased odds of common misdiagnosis conditions among NET cases compared with non-NET controls, contributing to unnecessary healthcare costs, supports the need for accurate identification of NET. SynopsisThe majority of patients with NET (70%) were previously misdiagnosed, occurring a median of 3.4 years before correct diagnosis. Total mean healthcare costs related to misdiagnoses were $2,858 PPPM and costs related to pancreatic adenocarcinoma misdiagnoses were substantial ($29,321 PPPM).

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015–2020)

Aims To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US. Materials and methods This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates. Results A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1–Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676–$24,597]) in 1 L, $30,027 ($20,868 [$13,416–$31,016]) in 2 L, and $47,064 ($25,689 [$15,555–$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1–Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534–$253,630]) and $28,466 ($23,696 [$15,466–$39,107]), respectively. Conclusions No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24months. Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months13-18 included 119 and 48 patients, respectively; and months19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months1-6; $26,840 versus $27,983, respectively, in months7-12; $22,899 versus $25,137 in months13-18; and $22,279 versus $27,947 in months19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months1-6; $25,144 versus $26,692, respectively, in months7-12; $21,645 versus $23,709 in months13-18; and $20,486 versus $25,515 in months19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months7 to 24.

Total cost of care of Medicare Advantage beneficiaries participating in an appointment-based model in a national pharmacy chain.

The appointment-based model (ABM) is a pharmacy service to improve medication-related health outcomes. ABM involves medication synchronization and medication review, plus other services such as medication reconciliation, medication therapy management, vaccine administration, and multimedication packaging. ABM can improve medication adherence, but the economic impact is unknown. To assess the effect of a national pharmacy chain's ABM program for Medicare Advantage beneficiaries on total cost of care (TCOC). This study analyzed administrative claims data from April 7, 2017, through February 29, 2020, for Medicare Advantage beneficiaries with Part D using a propensity score-matched cohort design. The national pharmacy chain provided a list of ABM participants. Eligibility criteria for the ABM and control (non-ABM) groups included age 65 years or older on the index date (initial participation, ABM; random fill date, control) and continuous enrollment from at least 6 months pre-index (baseline) date through at least 6 months post-index (follow-up) date. Medical inflation-adjusted (2020) TCOC was calculated as the sum of all health care spending from Medicare Advantage beneficiaries with Part D plan and patient paid amounts, standardized to per patient per month (PPPM), during the follow-up period. Secondary outcomes included medication adherence calculated across prevalent maintenance therapeutic classes using proportion of days covered (PDC). Each group contained 5,225 patients with balanced characteristics after matching: 64% female, 73% White, mean age 75 years, mean Quan-Charlson comorbidity index score 0.9, and hypertension and dyslipidemia, each >65%. Median baseline all-cause PPPM health care costs in the ABM and control groups, respectively, were $517 and $548 ($221 and $234 medical, $135 and $164 pharmacy). Baseline PDC of at least 80% was 83% in the ABM group and, similarly, 84% in the control group. The mean (SD) follow-up was 604 (155) days for the ABM group and 598 (151) days for the control group. During the follow-up period, the median PPPM TCOC for the ABM group was $656 and was $723 for the control group (P = 0.011). Median pharmacy costs were also significantly less in the ABM group ($161 vs $193, P < 0.001), whereas median medical costs were $328 in the ABM group and $358 among controls (P = 0.254). More patients in the ABM group were adherent during follow-up, with 84% achieving PDC of at least 80% vs 82% among controls (P = 0.009). The ABM program was associated with significantly lower follow-up median total costs (medical and pharmacy), driven primarily by pharmacy costs. More patients were adherent in the ABM program. Payers and pharmacies can use this evidence to assess ABM programs for their members.

Economic impact of longer treatment duration in first-line for HR+/HER2- metastatic breast cancer: A retrospective analysis.

1072 Background: Real-world treatment duration (TD) in the first line of therapy (1LOT) has demonstrated a strong correlation with progression-free survival (PFS). Increased TD for cancer patients (pts) in earlier lines has been linked to reduced healthcare costs by mitigating the need for costly therapies in subsequent lines, but the extent to which 1LOT costs vary based on the duration pts stay on treatment in 1LOT remains largely unknown. This study investigates the relationship between the TD of endocrine therapy (ET) plus CDK4/6 inhibition (CDKi) in 1LOT (serving as a proxy for PFS) and various healthcare cost measures incurred in 1LOT among newly diagnosed pts with HR+/HER2- metastatic breast cancer (mBC). Methods: Using the IQVIA PharMetrics Plus database, we identified adult women with newly diagnosed HR+/HER2- mBC whose 1LOT within 90 days of metastatic diagnosis (met dx) was ET + CDKi between 10/01/2016 - 06/30/2022. Pts with at least 6 months of follow-up post-met dx were included. The study followed pts from ET+ CDKi initiation until a switch, discontinuation, or a gap exceeding 90 days. Baseline characteristics were assessed 12 months before met dx. Healthcare costs (adjusted to 2022 USD) during the follow-up period were measured per patient per month (PPPM). TD was categorized based on percentile (p) distribution into six groups (&lt;10p; ≥10p to &lt;25p; ≥25p to &lt;50p; ≥50p to &lt;75p; ≥75p to &lt;90p; and ≥90p). Cost measures included total, inpatient (inp), outpatient (outp), ER, and pharmacy (rx) costs. Generalized linear and two-part models examined the relationship between various cost measures and TD, adjusting for age, region, payer type, and Elixhauser comorbidity index (ECI). Results: The study included 1,536 pts receiving ET+ CDKi in 1LOT, with a median age of 59. The median ET + CDKi TD in 1LOT was 23.7 months. PPPM costs were $18,716; $1,044; $2,899; $63; and $14,711 for total, inp, outp, ER, and rx services, respectively. Models results indicate lower PPPM total, inp, outp and ER costs as TD increases (Table). PPPM costs were higher for the bottom 10th p (shortest TD group) compared to the top 10th p (longest TD group)(difference $6,411; $2,735; $3,297; and $205 higher for total, inp, outp, and ER visits respectively). PPPM rx costs did not vary with TD. Conclusions: Real-world TD of ET+ CDKi closely aligns with PFS reported in ET + CDKi trials, further demonstrating a strong correlation with PFS. Prolonging TD in 1LOT yields significant cost savings, primarily driven by reductions in inp, outp, and ER costs. The results underscore the need for ongoing optimization of pts selection for 1LOT for HR+ mBC. The study findings also suggest that the economic evaluation of investigated treatments should take into account treatment duration. [Table: see text]

Real-world treatment patterns, healthcare resource utilization and costs of care among newly-diagnosed patients with HR+/HER2- metastatic breast cancer.

1073 Background: Current literature on the treatment patterns and economic burden among newly diagnosed patients (pts) with HR+/HER2- metastatic breast cancer (mBC) is outdated and may not adequately capture the rapidly evolving treatment landscape. This study addresses this gap by providing a contemporary and comprehensive summary of real-world treatment patterns, healthcare resource utilization (HRU) and cost of care among HR+/HER2- mBC pts, through their first 3 lines of treatment (LOT) following metastatic diagnosis (met dx). Methods: We retrospectively identified adult women with newly diagnosed HR+/HER2- mBC between 10/01/2016 - 06/30/2022 from the IQVIA PharMetrics Plus database. Pts were required to have≥ 6 months of follow up post met dx. The study classified pts hierarchically into mutually exclusive treatment categories across 3 LOTs following met dx: endocrine therapy only (ET), CDK4/6 inhibitor-based therapy (CDKi), alpelisib-based therapy (ALP), mTOR inhibitor-based therapy (mTOR), PARP inhibitor (PARPi), or chemotherapy (CT). Categories with &lt; 30 pts in each line or those with overlapping targeted treatments were grouped into “Others'' (OTH). Baseline characteristics were assessed in the 12 months prior to met dx. HRU and costs of care (in 2022 USD) were measured during the follow-up period and reported in per patient per month (PPPM). Results: The study included 2,449 pts, with 64.6%, 10.5%, 22.8%, 2.1% pts receiving CDKi, CT, ET and OTH in 1LOT, respectively. In 2LOT (n=1,164), 41% of pts received CDKi, 24% CT, 20% ET, 9% mTOR, 4% ALP and 3% OTH. In 3LOT (n=479), 44% of pts received CT, 21% CDKi, 15% ET, 9% mTOR, 6% ALP and 4% OTH. The median treatment duration in 1LOT was longest for pts receiving CDKi (23.5 months) compared to 17.1 months for ET. The PPPM total costs were $15,396, $16,955 and $17,853 in 1, 2 and 3LOT. In 1LOT, CDKi pts had the highest PPPM costs [Table]. In the 2/3 LOT, ALP-treated pts incurred the highest costs followed by CDKi in 2LOT and mTOR-treated pts in 3LOT (Table). CT and ALP had the highest ER visits in 2 (0.18 and 0.13) and 3 LOT (0.20 and 0.27). Conclusions: The majority of patients received CDKi treatment as their 1LOT with a more fragmented treatment landscape in the 2/3LOTs. The incorporation of agents targeting the PI3K pathway (ALP and mTOR) remained low in the 2/3LOTs. Costs associated with the same targeted treatment increased when used in later lines of therapy. Early optimization of targeted therapy and a focus on adverse event management may be associated with economic benefits. [Table: see text]

Differences in baseline characteristics and healthcare costs among insured patients with advanced cancer with vs without clinical trial participation.

11154 Background: Despite concerted efforts to improve clinical trial participation (CTP), enrollment remains low. Perceived additional costs to the patient or health plan may be barriers to CTP; low biomarker testing rates may be another. This study assessed differences in characteristics of patients with CTP versus patients without CTP in an insured population with advanced cancer. Methods: A retrospective analysis was conducted using de-identified administrative claims data from commercially insured and Medicare Advantage (MA) enrollees in the Optum Labs Data Warehouse. Patients ≥18y with claims evidence of advanced cancer and systemic therapy between 01/01/2018 and 02/28/2022 were stratified into 2 groups: 1) with CTP: ≥1 claim with a CTP diagnosis (ICD10 Z00.6) and ≥1 claim with a Q modifier on or within 90 days after index date; and 2) without CTP: no claims with a CTP diagnosis or Q modifier. Patients with &gt;1 primary cancer, T-cell therapy, or &lt;360 days baseline or follow-up (unless death) enrollment were excluded. Biomarker testing, targeted therapy use, and healthcare costs per patient per month (PPPM) were assessed in the baseline period. Results: Of 61,490 patients identified, 1753 (3%) had CTP and 59,737 (97%) did not have CTP; 4% of commercial and 3% of MA patients had CTP. Most common tumor types were breast (27%; 2% had CTP), lung (16%; 3% had CTP), digestive tract (15%; 2% had CTP), and prostate (15%; 3% had CTP). Patients with CTP were younger and more frequently had documented biomarker test use in the baseline period than patients without CTP (Table). In unadjusted analyses, the CTP group had higher healthcare costs in the baseline period prior to CTP regardless of insurance type, driven by 51% higher systemic cancer therapy costs and 35% higher ambulatory visit costs. An ongoing propensity score matched analysis will evaluate the impact of CTP on cost of care in the follow-up period. Conclusions: Consistent with prior studies, the overall CTP rate among patients with advanced cancers was low (3%). Baseline costs (prior to CTP) were higher for patients that later enrolled in clinical trials than for patients without CTP. Further research is ongoing to assess differences in follow-up healthcare costs for patients with vs without CTP adjusting for baseline characteristics. [Table: see text]

Real-world costs and outcomes associated with biomarker testing by comprehensive genomic profiling (CGP) and non-CGP approaches among patients with metastatic non-small cell lung cancer (mNSCLC).

e20598 Background: Guideline-recommended molecular testing is essential for identifying appropriate targeted therapies (Rx) for treatment of mNSCLC patients (pts). Biomarker testing can be performed by single gene tests, small NGS panels (e.g., &lt; 50 genes), or CGP approaches. There is little evidence on the rate of biomarker testing in the real world setting and the impact of different approaches on Rx utilization and cost of care. This study examined real-world utilization of biomarker testing among mNSCLC pts and outcomes with CGP and non-CGP testing. Methods: De-identified administrative claims data from the Optum Labs Data Warehouse were analyzed to identify newly diagnosed adult mNSCLC pts from 1/2018 to 8/2021; the date of the first claim indicating metastasis was the index date. Continuous enrollment in a commercial (COM) or Medicare Advantage (MA) plan with medical and pharmacy benefits for 12 mo prior to (baseline), and ≥6 mo post index date (follow-up) was required; pts with &lt; 6 mo follow-up due to death were included. Initiation of a line of therapy (LOT1) during follow-up was required. We categorized pts based on receipt and type of biomarker testing prior to LOT1: CGP ( &gt; 50 gene panel), non-CGP (5-50 gene panels or single gene testing), or no testing. Differences in receipt of targeted Rx, overall survival (OS), and total overall per patient per month (PPPM) costs during LOT1 were examined with multivariable regression analyses. Results: 9,945 mNSCLC pts (1,970 COM, 7,975 MA) were identified: 5,484 with no testing, 2,215 with CGP, and 2,246 with non-CGP testing prior to LOT1. Biomarker testing rates prior to LOT1 were low (45%) but increased during the study period from 42% to 48% (p &lt;0.01). Testing rates were higher for the COM vs MA population (49% vs 44%, p &lt;0.01). A higher percent of pts with CGP received targeted Rx compared to the non-CGP and no testing group (17% vs 11% and 5% respectively, p&lt; 0.01); after adjustment, CGP pts were still more likely to receive targeted Rx. Compared to the no testing group, OS was more favorable for the CGP [HR 0.8, 95% CI 0.8-0.9] and non-CGP [HR 0.9, 95% CI 0.8-0.9] groups. There was no significant difference in PPPM costs between tested groups: CGP [CR 1.2, 95%CI 1.1-1.2] vs non-CGP [CR 1.1, 95%CI 1.1-1.2]. Conclusions: Rates of biomarker testing among mNSCLC pts are far from optimal despite well-established guideline recommendations and insurance coverage for testing. There was evidence of improved intermediate outcomes (receipt of targeted Rx) with CGP compared to non-CGP or no testing. In addition, OS was improved for tested pts compared to untested. Interventions to help improve biomarker testing are needed. Given the potential benefits of CGP testing (including assessment of biomarkers that cannot be evaluated using small panels), increasing CGP testing may improve outcomes.

Treatment Patterns, Acute Healthcare Resource Use, and Costs of Patients with Treatment-Resistant Depression Completing Induction Phase of Esketamine in the United States.

This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly. Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods. Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2days in the main cohort and 78.8days in the subgroup (per label, 28days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar. Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior acute healthcare users.

Cost of disease progression among US patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

Aim: The objectives were to investigate the differences in per patient per month (PPPM) healthcare resource utilization (HCRU) and costs among commercially insured and Medicare Advantage patients with human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) who experience disease progression in 12months compared with those who don't investigate the impact of progression timing on cumulative healthcare costs. Patients & methods: This claims-based study included patients diagnosed with mBC between 1January 2013 and 30April 2020 and received HER2-targeted therapy. Patients were categorized as progressed or nonprogressed. For objective one, monthly HCRU and costs were assessed for up to two lines of therapy (LOTs). Data were summarized descriptively and compared using a generalized linear model (GLM). For objective two, patients with at least 6 months of follow-up were assessed and cumulative healthcare costs were estimated in the 3 years following the start of LOT1 or LOT2 using a GLM and Kaplan-Meier weighting. Results: Among the 4113 patients in the study sample, 3406 had at least 12 months of follow-up (or less if due to death). Compared with nonprogressed patients, progressed patients had higher mean PPPM healthcare costs (LOT1: $22,014 vs $18,372, p<0.001; LOT2: $19,643 vs $16,863, p=0.001), and HCRU, including number of emergency room visits and inpatient stays (both p<0.001) in the 12 months following LOT start. Progressed patients had higher 3-year mean cumulative healthcare costs than nonprogressed patients following LOT1 and LOT2 and this difference was greater for patients who progressed earlier. Conclusion: Disease progression was associated with significant increases in HCRU and costs. Delays in progression were associated with lower cumulative healthcare costs. Earlier use of more clinically effective treatments to delay progression may reduce the economic burden among these patients.

Real-World Health Care Resource Use and Costs Among Patients With Chronic Lymphocytic Leukemia Treated With Venetoclax-Based and Bruton Tyrosine Kinase Inhibitor-Based Regimens in the Second-Line Setting.

Real-world evidence comparing health care resource use (HRU) and costs between novel targeted therapies among patients with chronic lymphocytic leukemia (CLL) is lacking. We compared all-cause and CLL-specific HRU and costs between patients initiated on B-cell lymphoma 2 inhibitor (venetoclax)- or Bruton tyrosine kinase inhibitor (BTKi)-based regimens in the second-line (2L) setting. This is a retrospective observational study using Optum Clinformatics Data Mart of adult patients with CLL/small lymphocytic lymphoma who received 2L venetoclax- or BTKi-based regimens (January 2018-December 2021) for the first time and had ≥one CLL diagnostic claim after 2L initiation and ≥two claims for venetoclax or BTKi. Baseline characteristics were balanced using stabilized inverse probability of treatment weights. Mean monthly cost difference (MMCD) between cohorts for all-cause and CLL-specific per patient per month (PPPM) costs was estimated. Rates of PPPM-HRU were compared between cohorts using rate ratios (RRs). Of 280 patients, median age 75.5 years, 64.6% and 35.4% received BTKi- versus venetoclax-based regimens, respectively. Most BTKi-treated patients received monotherapy (88.4%), whereas 62.3% of venetoclax-treated patients received combination therapy with anti-CD20 agents. The median duration of 2L therapy was 11.6 and 11.0 months for BTKi versus venetoclax cohorts, respectively. All-cause total costs were lower for venetoclax versus BTKi (MMCD [SE], $-2,497.64 [$1,006.77] in US dollars (USD); P = .01), driven by lower medication costs offsetting medical costs; trends were similar for CLL-specific estimates. Outpatient HRU was higher for venetoclax versus BTKi (RR all-cause: 1.22 versus CLL-specific: 1.64). Venetoclax was associated with total monthly cost savings versus BTKis, illustrating the economic value of time-limited venetoclax-based regimens in the 2L setting.

Real-world clinical outcomes and healthcare costs in patients with Crohn’s disease treated with vedolizumab versus ustekinumab in the United States

Objective To compare real-world treatment persistence, dose escalation, rates of opportunistic or serious infections, and healthcare costs in patients with Crohn’s disease (CD) receiving vedolizumab (VDZ) vs ustekinumab (UST) in the United States. Methods A retrospective observational study in adults with CD initiated on VDZ or UST on/after 26 September 2016, was performed using the IBM Truven Health MarketScan databases (1 January 2009–30 September 2018). Rates of treatment persistence, dose escalation, opportunistic or serious infection–related encounters, and healthcare costs per patient per month (PPPM) were evaluated. Entropy balancing was used to balance patient characteristics between cohorts. Event rates were assessed using weighted Kaplan-Meier analyses and compared between cohorts using log-rank tests. Healthcare costs were compared between cohorts using weighted 2-part models. Results 589 VDZ and 599 UST patients were included (172 [29.2%] and 117 [19.5%] were bio-naïve, respectively). After weighting, baseline characteristics were comparable between cohorts. No significant difference in rates of treatment persistence (12-month: VDZ, 76.5%; UST, 82.1%; p = .17), dose escalation (12-month: VDZ, 29.3%; UST, 32.7%; p = .97), or opportunistic or serious infection–related encounters were observed between VDZ and UST. Total mean healthcare costs were significantly lower for patients treated with VDZ vs UST (mean cost difference = –$5051 PPPM; p < .01). Findings were consistent in bio-naïve patients. Conclusions In this real-world study, similar treatment persistence, dose escalation, and rates of opportunistic or serious infections were observed with VDZ- and UST-treated patients with CD. However, VDZ was associated with a significantly lower cost outlay for healthcare systems.

Clinical and economic outcomes associated with lymph node examination status in early-stage non-small cell lung cancer: a real-world US study using the SEER-Medicare linked database.

Clinical practice guidelines recommend adjuvant therapy for patients with early non-small cell lung cancer (eNSCLC), especially those with lymph node metastasis. This study evaluated the prevalence of lymph node examination and its association with adjuvant treatment rates, overall survival (OS), and healthcare costs among United States (US) Medicare patients with resected eNSCLC. This retrospective observational cohort study used Surveillance, Epidemiology, and End Results cancer registry data linked with Medicare claims data. Eligible patients were aged ≥65 years with newly diagnosed non-small cell lung cancer (NSCLC) stages IA to IIIB [the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 7th edition] between January 2010 and December 2017 with surgery ≤1 month prior to or ≤12 months after diagnosis. Patients were grouped by lymph node examination status: no examination (pNX), examination and no metastasis (pN0), or metastasis staging in N1 (pN1) or N2 (pN2). OS and costs were evaluated by examination status and number of lymph node examined. OS was analyzed using extended Cox proportional hazards models for specific time periods and time interaction with examination status, and adjusted for patient characteristics. Adjusted post-surgical healthcare costs per patient per month (PPPM) were analyzed using gamma-log regression models. Among the 14,648 patients included in the study, approximately 11% were pNX, whereas most were pN0 (68%), followed by pN1 (11%) and pN2 (10%). Adjuvant treatment rates were higher for pNX (35%) than pN0 (18%), but lower than pN1 (68%) and pN2 (74%) patients (P<0.001). Unadjusted OS for pNX patients was nearly identical to pN2, and significantly worse compared to pN0 and pN1 (P<0.0001). After adjusting for patient characteristics, pNX patients had higher risk of death relative to pN0 patients (P<0.001). Marginal mean adjusted total costs were comparable across pNX ($15,827 PPPM), pN0 ($12,712 PPPM) and pN1 ($17,089 PPPM), but significantly less for pN0 compared to pN2 ($23,566 PPPM) (P=0.002). Inadequate lymph node examination is associated with underutilization of adjuvant treatment and poor OS in resected NSCLC. In the current era of targeted and immunotherapies, lymph node examination is more important than ever, implicating the need for Quality Improvement practices and multidisciplinary coordination.

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.

Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had≥ 12months of continuous enrollment prior to initiation (preindex period) and ≥ 6months of data following initiation (postindex period; variable follow-up after 6months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6months postindex. Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article.

Incidence and Costs of Clinically Significant Events with Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Cohort Study.

Systemic therapies have been associated with clinically significant events (CSEs) in patients with unresectable hepatocellular carcinoma (uHCC). We evaluated the incidence of CSEs (bleeding, clotting, encephalopathy, and portal hypertension), and their impact on healthcare resource utilization (HCRU) and costs, in patients with uHCC treated with first-line (1L) atezolizumab plus bevacizumab (A + B), lenvatinib (LEN), or sorafenib (SOR) in the USA. A retrospective cohort study was performed using medical/pharmacy claims from Optum® Clinformatics® Data Mart. Patients diagnosed with HCC who initiated 1L A + B between June 01, 2020 and December 31, 2020 or LEN/SOR between January 01, 2016 and May31, 2020 were included. Outcomes included incidence rates of CSEs, HCRU, and costs. Subgroup analysis was performed in patients with no CSEs or ≥ 1 CSE. In total, 1379 patients were selected (A + B, n = 271; LEN, n = 217; SOR, n = 891). Clotting (incidence rate per 100 patient-years [PY] 94.9) and bleeding (88.1 per 100 PY) were the most common CSEs in the A + B cohort. The most common CSEs in the LEN cohort were clotting (78.6per 100 PY) and encephalopathy (66.3 per 100 PY). Encephalopathy (73.0per 100 PY) and portal hypertension (72.3 per 100 PY) were the most common CSEs in the SOR cohort. Mean total all-cause healthcare costs per patient per month (PPPM) were $32,742, $35,623, and $29,173 in the A + B, LEN, and SOR cohorts, respectively. Mean total all-cause healthcare costs PPPM were higher in patients who had ≥ 1 CSE versus those who did not (A + B $34,304 versus $30,889; LEN $39,591 versus $30,621; SOR $31,022 versus $27,003). Despite improved efficacy of 1L systemic therapies, CSEs remain a concern for patients with uHCC, as well as an economic burden to the healthcare system. Newer treatments that reduce the risk of CSEs, while improving long-term survival in patients with uHCC, are warranted.

Epidemiology, treatment patterns, and humanistic and economic burden of biliary tract carcinoma: A systematic and targeted literature review.

443 Background: Patients with biliary tract cancers (BTC) are typically diagnosed at late stage, with limited treatment options. As such, BTC is associated with poor prognosis, high economic burden and reduced health-related quality of life (HRQoL). As the treatment paradigm is evolving, with multiple immunotherapies showing promise, this study aimed to assess the current disease and treatment landscape. Methods: Systematic literature reviews (Embase, MEDLINE, Cochrane, NHS-EED; database inception to Feb 10, 2023) were conducted for HRQoL and economic burden. Targeted literature reviews (Embase, MEDLINE) were conducted for epidemiology (Jan 01 2017–Feb 06 2023) and treatment guidelines/patterns (Jan 01 2012–Feb 06 2023). Conference abstracts were also searched (2019–2022). Eligibility criteria included global studies (English language) in adults with metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epidemiology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39–8.78 and 9.1–10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02–0.34% and 0.02–2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine [gem]-based chemotherapy was most common in 1L BTC (24–100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3–74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7–14.8 months and 7–16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifications. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based combinations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589–25,517, 2L: $22,617–29,721, 3L: $23,256–33,534). US healthcare resource utilization in 1L was driven by outpatient visits (98%), emergency department visits (33–80%) and hospitalization (70–80%). Mean hospital stay ranged from 0.6–7 days PPPM. Conclusions: Epidemiology data varied between Western and Asian populations, but gem-based chemotherapy was identified as the standard of care across regions. There is high unmet need in advanced BTC, as existing options are characterized by poor survival outcomes and considerable economic burden. These findings indicate a need for novel approaches for the management of BTC.

Incremental Burden Associated with Dose Escalation in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Complement Inhibitors

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by complement-mediated hemolytic anemia. Terminal complement component C5 inhibitors eculizumab (ECU) and ravulizumab (RAVU) inhibit the formation of membrane attack complex, and thereby ameliorates intravascular hemolysis in PNH. Some patients exhibit breakthrough intravascular hemolysis near the end of 14-day treatment cycle for ECU or 8-week treatment cycle for RAVU. To manage breakthrough hemolysis, different treatment strategies may be attempted in the clinical practice, including shortening the dosing interval and/or increasing the dose of ECU and RAVU. This study aimed to estimate the incremental costs associated with dose escalation in patients with PNH treated with ECU or RAVU in the US. Methods: Adult (age ≥18 years) patients with PNH (ICD-10-CM code D59.5) treated with ECU or RAVU from health plan claims data (01/01/2011 to 09/30/2022) with ≥3 months of continuous health plan coverage following the first claim for ECU or RAVU were included in this retrospective cohort study. Dosing patterns were investigated during the maintenance phase. Consistent with label-recommended dosing schedule, the maintenance phase started from day 29 and day 15 post-first claim for ECU and RAVU, respectively, until the earliest of treatment discontinuation/loss to follow-up/end of data. Dose escalation for ECU was defined as 1) an increased dose (i.e., 1,200 or 1,500 mg) and/or 2) an increased infusion frequency (i.e., ≥2 infusions within 12 days). Patient-weight information was not available; dose escalation for RAVU was defined as an increased infusion frequency (i.e., ≥2 infusions within 49 days). All-cause and PNH-related direct healthcare costs measured during maintenance phase for the overall cohort and subgroup of patients with dose escalation were assessed for ECU and RAVU separately. Incremental costs associated with dose escalation in the pre vs. post dose escalation period were assessed for ECU and RAVU separately; p-values from Wilcoxon signed-rank tests were reported. Results: A total of 278 patients treated with ECU (mean± SD age, 42±13 years; 60% female) were included in the overall cohort and a subgroup of 151 patients were observed with a dose escalation (mean±SD age, 41±13 years; 58% female). For the overall ECU cohort (N=278), during a mean follow-up of 23 months, total all-cause and PNH-related costs (mean±SD) were $67,650±$32,518 and $65,751±$31,379 per patient per month (PPPM), respectively. In the subgroup of patients with dose escalation (N=151), over a mean follow-up of 30 months, total all-cause and PNH-related costs (mean±SD) were $71,466±$33,452 and $69,471±$31,595 PPPM, respectively. In the overall cohort and subgroup of patients with dose escalation, PNH-related treatment costs represented 90% and 92% of total all-cause costs respectively. A total of 171 patients treated with RAVU (mean± SD age, 39±12 years; 43% female) were included in the overall cohort and a subgroup of 26 patients were observed with a dose escalation (i.e., increased infusion frequency only) (mean± SD age, 37±11 years; 54% female). For the overall RAVU cohort (N=171), during a mean follow-up of 17 months, total all-cause and PNH-related costs (mean±SD) were $50,779±$26,258 and $49,213±$25,751 PPPM, respectively. In the subgroup of patients with dose escalation (N=26), over a mean follow-up of 20 months, total all-cause and PNH-related costs (mean±SD) were $52,819±$20,965 and $50,740±$20,837 PPPM, respectively. In the overall cohort and subgroup of patients with dose escalation, PNH-related treatment costs represented 93% and 91% of total all-cause costs, respectively. Incremental costs (mean cost differences) associated with dose escalation for ECU were of $16,861 (p&amp;lt;0.01) and $15,956 (p&amp;lt;0.01) PPPM for all-cause and PNH-related total costs, respectively; and for RAVU were of $4,950 (p&amp;lt;0.05) and $3,738 (p=0.06) PPPM for all-cause and PNH-related total costs, respectively (Figures 1A and 1B). Conclusions: In this study of PNH patients treated with C5 inhibitors, dose escalation was associated with significant incremental costs for both ECU and RAVU. Further research is warranted to clarify the reasons for dose escalation, which may potentially indicate an unmet clinical need for more efficacious treatment options to help prevent breakthrough symptoms and reduce the burden of PNH.