Healthcare Resource Utilization and Costs in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer Receiving First-Line Treatment in the United States: An Insurance Claims-Based Descriptive Analysis.

BACKGROUND: An estimated 10-15% of non-small cell lung cancer (NSCLC) cases present with epidermal growth factor receptor mutation (EGFRm). While EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as osimertinib have become first-line (1L) standard of care for these patients, limited chemotherapy use still occurs in real-world practice. Studies of healthcare resource use (HRU) and cost of care provide a means by which the value of various treatment regimens, healthcare efficiency, and disease burden can be assessed. These studies are important for population health decision makers and health systems that prioritize value-based care to drive population health. OBJECTIVE: The aim of this study was to descriptively assess HRU and costs among patients with EGFRm advanced NSCLC initiating 1L therapy in the United States. METHODS: IBM MarketScan Research Databases (January 1, 2017 to April 30, 2020) were used to identify adult patients with advanced NSCLC, based on a diagnosis for lung cancer (LC) and initiation of 1L therapy or diagnosis of metastases within 30 days of the first LC diagnosis. All patients had ≥ 12 months of continuous insurance eligibility prior to the first LC diagnosis and initiated (in 2018 or after) an EGFR-TKI during any line of therapy to proxy EGFRm status. Per-patient-per-month all-cause HRU and costs were described during 1L for patients initiating 1L osimertinib or chemotherapy. RESULTS: A total of 213 patients with advanced EGFRm NSCLC were identified (mean age at 1L initiation: 60.9 years; 69.0% female). In 1L, 66.2% initiated osimertinib, 21.1% chemotherapy, and 12.7% another regimen. Mean 1L therapy duration was 8.8 months (osimertinib) and 7.6 months (chemotherapy), respectively. Among osimertinib recipients, 28% had an inpatient admission, 40% an emergency room (ER) visit, and 99% an outpatient visit. Among chemotherapy recipients, these proportions were 22%, 31%, and 100%. Mean monthly all-cause healthcare costs among osimertinib and chemotherapy patients were US$27,174 and US$23,343, respectively. Among osimertinib recipients, drug-related costs (including pharmacy and outpatient antineoplastic drug and administration costs) made up 61% (US$16,673) of total costs, inpatient costs 20% (US$5462), and other outpatient costs 16% (US$4432). In chemotherapy recipients, 59% (US$13,883) of total costs were drug-related, 5% (US$1166) were inpatient costs, and 33% (US$7734) other outpatient costs. CONCLUSIONS: Higher mean total cost of care was observed among patients receiving 1L TKI (osimertinib) than 1L chemotherapy in EGFRm advanced NSCLC. However, descriptive differences in type of spending and HRU were identified: higher inpatient costs and inpatient days for osimertinib versus higher outpatient costs for chemotherapy. Findings suggest that significant unmet needs may remain for 1L treatment of EGFRm NSCLC, and despite significant advances in targeted care, further individualized therapies are needed to balance benefits, risks, and total cost of care. Furthermore, observed descriptive differences in inpatient admissions may have implications for quality of care and patient quality of life, for which additional research is warranted.

Comparison of clinical outcomes in patients with schizophrenia following different long-acting injectable event-driven initiation strategies.

This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring-strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1-4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2-4, respectively; the clinical benefit was also observed for strategy #2 vs #3-4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.

Projecting the economic outcomes of switching patients with schizophrenia from oral atypical antipsychotics to once-monthly, once-every-3-months, and once-every-6-months paliperidone palmitate.

BACKGROUND: Among patients with schizophrenia, nonadherence to oral atypical antipsychotics (OAAs) leads to increased risk of relapses, which entails substantial economic burden. OBJECTIVE: To evaluate the impact on health care costs and relapse rates of switching patients with schizophrenia from OAAs to once-monthly paliperidone palmitate (PP1M), with subsequent transitions to once-every-3-months (PP3M) and once-every-6-months paliperidone palmitate (PP6M). METHODS: A 36-month Markov model was developed from a Medicaid payer's perspective. Two non-mutually exclusive subpopulations of adults with schizophrenia who were nonadherent to OAAs were considered: (1) recently relapsed and (2) young adults (aged 18-35). Patients were assumed nonadherent to OAAs until switching treatments, which was permissible multiple times during the 36-month period. Patients switching to PP1M could subsequently transition to PP3M and PP6M. Relapse rates were assumed consistent across treatments based on patients' adherence. Model inputs were literature based. PP6M transition rates were assumed similar to PP3M. Cost savings were reported at the plan level and per patient switched. RESULTS: In a hypothetical health plan of 1 million Medicaid beneficiaries, an estimated 10,053 adults with schizophrenia were nonadherent to OAAs, among whom 7,454 were recently relapsed and 4,002 were young adults. Switching 5% of recently relapsed adults (N = 373) from OAAs to PP1M prior to subsequent relapse resulted in 541 relapses avoided and plan-level savings of $8.2M after 3 years. Incorporating transitions to PP3M/PP6M increased net savings to $9.1M and 631 relapses were avoided. Among young adults, switching 5% (N = 200) from OAAs to PP1M saved $1.8M at the plan level with 178 relapses avoided after 3 years. Including transitions to PP3M/PP6M, 3-year plan-level savings were $2.0M with 223 relapses avoided. Per recently relapsed patient switched to PP1M, and subsequently to PP3M/PP6M, cumulative 3-year cost savings were $22,100 and $24,300, respectively. Among young adults, corresponding 3-year cost savings per patient were $8,900 and $9,800. CONCLUSIONS: Switching nonadherent patients from OAAs to PP1M results in substantial cost savings and reduces relapse rates. Incorporating transitions to PP3M/PP6M leads to incremental cost savings and additional relapses avoided. DISCLOSURES: Financial support for this research was provided by Janssen Scientific Affairs, LLC. Ms Morrison, Ms Ghelerter, Ms Vermette-Laforme, Mr Lefebvre, and Mr Pilon are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC., which funded the development and conduct of this study and manuscript. Dr Lin and Ms Benson are employees of Janssen Scientific Affairs, LLC., and stockholders of Johnson & Johnson.

Real-world utilization and outcomes of systemic therapy among patients with advanced or recurrent endometrial cancer in the United States.

OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States. METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line of therapy were evaluated. To account for new drug approvals, patients first treated in 2018 or 2019 were also assessed separately. RESULTS: Among the 1317 patients who met all eligibility criteria, 520 (39.5%) and 235 (17.8%) patients received 3 or 4+ lines of treatment, respectively, during a median total follow-up time of 25.2 months (range, 2.5-173.3 months) following the index date. Chemotherapy, including platinum- and non-platinum-based regimens, was the most common treatment across all lines of therapy: 2L, 80.0%; 3L, 66.2%; 4L+, 80.4%. Overall, 2.5%, 2.3%, and 8.9% of 2L, 3L, and 4L + patients, respectively, received anti-program death 1 (anti-PD-1) immunotherapies. In patients first treated in 2018 and 2019 (n = 163), 9.8% of patients received anti-PD-1 immunotherapy in the 2L. In the overall population, median time to next treatment (TTNT) was 19.3, 10.5, and 8.1 months for patients undergoing 2L, 3L, and 4L treatment, respectively. CONCLUSIONS: Among patients with advanced/recurrent EC treated with 1L platinum-based therapy in clinical practice, chemotherapy was the most common treatment choice across all lines of therapy. Immunotherapy use was low overall but increased in patients who started treatment in 2018 or 2019. Overall, median TTNT decreased as lines of therapy increased.

Patient characteristics, treatment patterns, and outcomes among black and white patients with multiple myeloma initiating daratumumab: A real-world chart review study.

BACKGROUND: Daratumumab was approved for multiple myeloma (MM) in 2015. While its safety and efficacy are well documented, there is limited real-world information on its use and outcomes in patients of different races. METHODS: We conducted a retrospective chart review of adult patients with MM initiating daratumumab in any line of therapy (LOT) between November 2015 and May 2020. De-identified data were retrieved from 2 US clinical sites; patient characteristics, treatment patterns, and response rate were described for black and white patients, stratified by LOT. Overall response rate (ORR), progression-free survival (PFS), and time to next LOT (TTNT) were compared between black and white patients initiating daratumumab in second line (2L) or later, adjusting for age and number of prior lines. RESULTS: Two hundred and fifty-two patient charts (89 black, 163 white) were extracted. Black patients were younger at diagnosis (61.7 vs. 67.0 years) and had a similar proportion of females (black: 44.9%, white: 46.6%). Black patients had longer time between MM diagnosis and daratumumab initiation (43.2 vs. 34.1 months) and received more prior LOTs (median 3.0 vs. 2.0). ORR for black and white patients initiating daratumumab in 1L was 100.0%, with very good partial response or better in 75.0% and 66.7%, respectively. Similar trends were observed in 2L and 3L+. There were no significant differences in ORR, PFS, or TTNT between groups. CONCLUSION: Daratumumab had similar clinical outcomes (ORR, PFS, and TTNT) in black and white patients. Black patients initiated daratumumab later in their treatment, suggesting potential discrepancies in access to new MM treatments.

Medication adherence among patients with advanced prostate cancer using oral therapies.

Aims: In light of the extended overall survival and improved quality of life provided by advanced prostate cancer (PC) oral therapies, this study aimed to describe treatment adherence to advanced PC oral therapies and evaluate associated patient characteristics and subsequent healthcare resource utilization (HRU). Patients & methods: Patients with advanced PC initiating apalutamide, enzalutamide or abiraterone acetate were identified from administrative data (October 1, 2014-September 30, 2019). Adherence and persistence at six months postinitiation were used to evaluate patient factors and HRU. Results: Aged ≥75 years, Black race, chemotherapy use and higher pharmacy paid amounts were associated with poor adherence/persistence, which translated to higher HRU. Conclusions: Strategies to increase adherence and persistence may improve patient outcomes and associated HRU.

Lay abstract This study included 27,262 patients with advanced prostate cancer who started taking one of three oral cancer medications (apalutamide, enzalutamide or abiraterone acetate) between October 2014 and September 2019. Patients who were black, aged 75 years or older, who had chemotherapy or who had higher prescription costs had the most difficulty following dosing guidelines or staying on treatment. Patients who did not follow dosing guidelines required more healthcare services. In light of the extended survival and improved quality of life that oral cancer medication for advanced prostate cancer provides, helping patients to take the correct medication dose, at the right time, and for the recommended length of time may improve their outcomes and reduce medical costs.

Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study.

BACKGROUND: Daratumumab, a CD38 monoclonal antibody, has demonstrated efficacy as monotherapy and combination therapy across several indications, both among newly-diagnosed and refractory patients with multiple myeloma (MM). However, there is limited evidence on treatment patterns and effectiveness of daratumumab in the real-world setting, particularly in first line (1 L). This study aimed to describe real-world treatment patterns and clinical outcomes among patients initiating daratumumab across different lines of therapy. METHODS: A retrospective chart review of adult patients with MM initiating daratumumab between November 2015 and March 2021 was conducted at two clinical sites in the United States. De-identified patient-level data were abstracted in an electronic case report form. Patient characteristics and treatment patterns were described. Clinical outcomes including overall response rate (ORR), progression-free survival, and time to next line of therapy were reported using descriptive statistics and stratified by line of therapy (1 L, second line [2 L] or third line or later [3 L+]). A sub-group analysis evaluated treatment patterns and ORR among patients re-treated with daratumumab. RESULTS: A total of 299 patients were included in the study (mean age: 68 years; 55% male). Among them, 26 were 1 L patients, 66 were 2 L patients, and 207 were 3 L+ patients; 110 patients (36.8%) received a stem cell transplant prior to daratumumab initiation. The mean duration of follow-up was 10 months among 1 L patients and 19 months among 2 L and 3 L+ patients. Patients who initiated daratumumab in 1 L had a 100% ORR, while those initiating in 2 L and 3 L+ had an ORR of 78.8 and 65.2%, respectively. Among re-treated patients, ORR was 66.7% during the first treatment segment, and 52.9% during the second treatment segment. Kaplan-Meier rates of progression-free survival at 12 months were 89.9, 75.2, and 53.1% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. Kaplan-Meier rates of time to next line of therapy at 12 months were 94.1, 73.4, and 50.0% among patients who initiated daratumumab in 1 L, 2 L, and 3 L+, respectively. CONCLUSIONS: These findings suggest that daratumumab-based regimens are an effective treatment option across all lines of therapy, with highest response rate in 1 L.

The Prevalence and National Burden of Treatment-Resistant Depression and Major Depressive Disorder in the United States.

OBJECTIVE: Estimates of prevalence and burden of treatment-resistant depression (TRD) vary widely in the literature. This study evaluated the prevalence and burden of TRD and the share of TRD in the burden of medication-treated major depressive disorder (MDD) using the most commonly accepted definition of TRD and a novel bottom-up approach. METHODS: Prevalence and health care burden of TRD were estimated by synthetizing inputs across 4 similarly designed claims studies in adults covered by Medicare, Medicaid, commercial plans, and the US Veterans Health Administration (VHA). Productivity (absenteeism and presenteeism) and unemployment burden were estimated based on inputs from a study conducted with data from the Kantar National Health and Wellness Survey (NHWS; 2017). A targeted literature search for additional inputs was performed. A cost model was developed to estimate the burden of TRD and medication-treated DSM-5-defined MDD in the United States. Study outcomes were the 12-month prevalence of TRD and the annual health care, productivity, and unemployment burden of TRD and medication-treated MDD in the United States. RESULTS: The estimated 12-month prevalence of medication-treated MDD in the United States was 8.9 million adults, and 2.8 million (30.9%) had TRD. The total annual burden of medication-treated MDD among the US population was $92.7 billion, with $43.8 billion (47.2%) attributable to TRD. The share of TRD was 56.6% ($25.8 billion) of the health care burden, 47.7% ($8.7 billion) of the unemployment burden, and 32.2% ($9.3 billion) of the productivity burden of medication-treated MDD. CONCLUSIONS: TRD is associated with disproportionate health care costs and unemployment, suggesting potentially large economic and societal gains with effective management.

Real-World Evidence of the Clinical and Economic Impact of Long-Acting Injectable Versus Oral Antipsychotics Among Patients with Schizophrenia in the United States: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-acting injectable (LAI) antipsychotics, compared with oral antipsychotics (OA), have been found to significantly improve patient outcomes, including reduced hospitalizations and emergency room (ER) admissions and increased medication adherence among adult patients with schizophrenia. In turn, the clinical benefits achieved may translate into lower economic burden. Real-world evidence of the comparative effectiveness of LAI is needed to understand the potential benefits of LAI outside of the context of clinical trials. This study aimed to provide a comprehensive synthesis of recent published real-world studies comparing healthcare utilization, costs, and adherence between patients with schizophrenia treated with LAI versus OA in the United States. METHODS: In this systematic literature review, MEDLINE® was searched for peer-reviewed, real-world studies (i.e., retrospective or pragmatic designs) published in English between January 1, 2010 and February 10, 2020. Comparative studies reporting hospitalizations, ER admissions, healthcare costs, or medication adherence (measured by proportion of days covered [PDC]) in adults with schizophrenia treated with LAI versus OA (or pre- vs post-LAI initiation) in the United States were retained. Random effects meta-analyses were conducted among eligible studies to evaluate the association of LAI versus OA use on hospitalizations, ER admissions, healthcare costs, and treatment adherence. A sensitivity analysis among the subset of studies that compared OA with paliperidone palmitate once monthly (PP1M), specifically, was conducted. RESULTS: A total of 1083 articles were identified by the electronic literature search, and two publications were manually added subsequently. Among the 57 publications meeting the inclusion criteria, 25 provided sufficient information for inclusion in the meta-analyses. Compared with patients treated with OA, patients initiated on LAI had lower odds of hospitalization (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.54-0.71, n = 7), fewer hospitalizations (incidence rate ratio [IRR] [95% CI] 0.75 [0.65-0.88], n = 9), and fewer ER admissions (IRR [95% CI] 0.86 [0.77-0.97], n = 6). The initiation of LAI was associated with higher per-patient-per-year (PPPY) pharmacy costs (mean difference [MD] [95% CI] $5603 [3799-7407], n = 6), which was offset by lower PPPY medical costs (MD [95% CI] - $5404 [- 7745 to - 3064], n = 6), resulting in no significant net difference in PPPY total all-cause healthcare costs between patients treated with LAI and those treated with OA (MD [95% CI] $327 [- 1565 to 2219], n = 7). Patients initiated on LAI also had higher odds of being adherent to their medication (PDC ≥ 80%; OR [95% CI] 1.89 [1.52-2.35], n = 9). A sensitivity analysis on a subset of publications evaluating PP1M found results similar to those of the main analysis conducted at the LAI class level. CONCLUSIONS: Based on multiple studies with varying sub-types of patient populations with schizophrenia in the United States published in the last decade, this meta-analysis demonstrated that LAI antipsychotics were associated with improved medication adherence and significant clinical benefit such as reduced hospitalizations and ER admissions compared with OA. The lower medical costs offset the higher pharmacy costs, resulting in a non-significant difference in total healthcare costs. Taken together, these findings provide strong evidence on the clinical and economic benefits of LAI compared with OA for the treatment of schizophrenia in the real world.

Antipsychotic Adherence, Resource Use, and Costs Before and After the Initiation of Once-monthly Paliperidone Palmitate Therapy Among Medicaid Beneficiaries With Prior Schizophrenia Relapse.

PURPOSE: Patients with schizophrenia often struggle with medication adherence and may benefit from the use of a long-acting injectable antipsychotic, including once-monthly paliperidone palmitate (PP1M), which was previously demonstrated to improve outcomes compared with oral antipsychotics. This study assessed the impact of initiating PP1M therapy on medication adherence, health care resource use (HRU), and costs among Medicaid beneficiaries with schizophrenia and a prior schizophrenia relapse. METHODS: A 6-state Medicaid database (from quarter 1 of 2009 to quarter 1 of 2018) was used to identify adults with ≥2 schizophrenia diagnoses who started PP1M therapy on or after January 1, 2010. The index date was the first PP1M claim. Patients had ≥12 months of continuous Medicaid enrollment before and after the index date, ≥1 oral antipsychotic claim in the 12 months before the index date, and ≥1 relapse (proxied as a schizophrenia-related inpatient admission or emergency department [ED] visit) during the 12 months before the index date. Generalized estimating equations were used to compare adherence to antipsychotics (proportion of days covered ≥80%), HRU, and costs (reported in 2018 US dollars) in the 12 months after versus before the index date. Sensitivity analyses were conducted (1) accounting for the minimum and cumulative price inflation Medicaid rebates for pharmacy costs of branded psychiatric medications, (2) among patients with ≥2, ≥3, and ≥4 prior schizophrenia-related inpatient admissions or ED visits, (3) among patients not adherent to antipsychotic treatment before the index date, and (4) among patients switching to PP1M directly from oral risperidone or paliperidone. FINDINGS: A total of 1725 patients met the study inclusion criteria (mean age, 39.5 years; 43% female). After versus before the index date, patients were 93% more likely to be adherent to antipsychotic treatment (P < 0.01). The likelihood of inpatient admissions and ED visits decreased by 89% and 49% (all P < 0.01) after initiating PP1M therapy. The number of inpatient days decreased by 31% (P < 0.01) and the number of ED visits by 16% (P = 0.03). Pharmacy costs increased by $514 per-patient-per-month (PPPM), whereas medical costs, driven by inpatient costs, decreased by $391 PPPM (all P < 0.01). Sensitivity analyses yielded similar trends. Notably, total health care cost savings of $231 PPPM were observed after accounting for the cumulative Medicaid rebate for costs of branded psychiatric medications (P < 0.01). IMPLICATIONS: In Medicaid beneficiaries with relapsed schizophrenia, transitioning from oral antipsychotics to PP1M was associated with improved adherence to antipsychotics and decreased use of inpatient and ED services. Increased pharmacy costs after the initiation of PP1M were offset by decreased medical costs. After applying the cumulative Medicaid rebate, including the price inflation rebate for costs of branded psychiatric medications, initiation of PP1M therapy resulted in statistically significant health care cost savings.