Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Treatment of Renal Cell Carcinoma Post-nephrectomy in the United States.

INTRODUCTION: Pembrolizumab was recently approved as an adjuvant treatment of renal cell carcinoma (RCC), based on prolonged disease-free survival compared to placebo in the phase III KEYNOTE-564 trial. The objective of this study was to evaluate the cost-effectiveness of pembrolizumab as monotherapy in the adjuvant treatment of RCC post-nephrectomy, from a US health sector perspective. PATIENTS AND METHODS: A Markov model with 4 health states (disease-free, locoregional recurrence, distant metastases, and death) was developed to compare the cost and effectiveness of pembrolizumab versus routine surveillance or sunitinib. Transition probabilities were estimated using patient-level KEYNOTE-564 data (cutoff: June 14, 2021), a retrospective study, and published literature. Costs of adjuvant and subsequent treatments, adverse events, disease management, and terminal care were estimated in 2022 US$. Utilities were based on EQ-5D-5L data collected in KEYNOTE-564. Outcomes included costs, life-years (LYs), and quality-adjusted LYs (QALYs). Robustness was assessed through one-way and probabilistic sensitivity analyses. RESULTS: Total cost per patient was $549,353 for pembrolizumab, $505,094 for routine surveillance, and $602,065 for sunitinib. Over a lifetime, pembrolizumab provided gains of 0.96 QALYs (1.00 LYs) compared to routine surveillance, yielding an incremental cost-effectiveness ratio of $46,327/QALY. Pembrolizumab dominated sunitinib with 0.89 QALYs (0.91 LYs) gained while saving costs. At a $150,000/QALY threshold, pembrolizumab was cost-effective versus both routine surveillance and sunitinib in 84.2% of probabilistic simulations. CONCLUSION: Pembrolizumab is projected to be cost-effective as an adjuvant RCC treatment versus routine surveillance or sunitinib based on a typical willingness-to-pay threshold.

Disease-free survival as a predictor of overall survival in localized renal cell carcinoma following initial nephrectomy: A retrospective analysis of Surveillance, Epidemiology and End Results-Medicare datac.

OBJECTIVES: This study aimed to assess whether disease-free survival (DFS) may serve as a predictor for long-term survival among patients with intermediate-high risk or high risk renal cell carcinoma (RCC) post-nephrectomy when overall survival (OS) is unavailable. METHODS: The Surveillance, Epidemiology and End Results-Medicare database (2007-2016) was used to identify patients with non-metastatic intermediate-high risk and high risk RCC post-nephrectomy. Landmark analysis and Kendall's τ were used to evaluate the correlation between DFS and OS. Multivariable regression models were used to quantify the incremental OS post-nephrectomy associated with increased time to recurrence among patients with recurrence, adjusting for baseline covariates. RESULTS: A total of 643 patients were analyzed; mean age of 75 years; >95% of patients had intermediate-high risk RCC at diagnosis; 269 patients had recurrence post-nephrectomy. For patients with versus without recurrence at the landmark points of 1, 3, and 5 years post-nephrectomy, the 5-year OS were 37.0% versus 70.1%, 42.3% versus 72.8%, and 53.2% versus 78.6%, respectively. The Kendall's τ between DFS and OS post-nephrectomy was 0.70 (95% CI: 0.65, 0.74; p < 0.001). After adjusting for baseline covariates, patients with one additional year of time to recurrence were associated with 0.73 years longer OS post-nephrectomy (95% CI: 0.40, 1.05; p < 0.001). CONCLUSION: The significant positive association of DFS and OS among patients with intermediate-high risk and high risk RCC post-nephrectomy from this study supports the use of DFS as a potential predictor of OS for these patients when OS data are immature.

Clinical and economic burdens of recurrence following nephrectomy for intermediate high- or high-risk renal cell carcinoma: A retrospective analysis of Surveillance, Epidemiology, and End Results-Medicare data.

BACKGROUND: Renal cell carcinoma (RCC) is associated with a high risk of recurrence. Although RCC has been shown to impose a substantial burden on patients, little is known about the incremental clinical and economic burden attributable to disease recurrence. With recent advances in the RCC-therapeutic landscape, including adjuvant therapies, it is important to quantify the clinical and economic burden associated with RCC recurrence to better evaluate the potential impact of treatment in this patient population. OBJECTIVE: To quantify the incremental clinical and economic burden associated with disease recurrence among patients with intermediate high-risk and high-risk RCC postnephrectomy. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2016) were used to identify patients with newly diagnosed, intermediate high-risk or high-risk RCC following nephrectomy. Patients with a diagnosis of metastatic disease or repeat nephrectomy or initiating a systemic treatment for advanced RCC were grouped as the recurrence cohort; patients without evidence of recurrence were grouped as the cohort without recurrence. Health care resource utilization (HRU), health care costs (2019 US dollars), and overall survival (OS) were compared between cohorts with and without recurrence, adjusting for demographic and clinical characteristics. RESULTS: A total of 269 patients with recurrence and 374 patients without recurrence were analyzed. Mean age was 75.2 and 75.7 years (P = 0.383), respectively, and 64.7% and 57.8% (P = 0.076) of patients were male, respectively. Median follow-up duration was 17 and 28 months, respectively. Patients with recurrence had a significantly shorter OS relative to patients without recurrence (adjusted hazard ratio = 6.00; 95% CI = 4.24-8.48; P < 0.001). Additionally, compared with patients without recurrence, patients with recurrence had significantly more inpatient admissions (0.16 vs 0.04 admissions per person-month [PM]; adjusted incidence rate ratio [aIRR] = 3.88; 95% CI = 3.12-4.81), outpatient visits (3.06 vs 1.77 visits per PM; aIRR = 1.68; 95% CI = 1.56-1.81), emergency department visits (0.10 vs 0.05 visits per PM; aIRR = 2.11; 95% CI = 1.66-2.68), and days hospitalized (1.40 vs 0.35 days per PM; aIRR = 6.73; 95% CI = 4.95-9.15) per patient per month (all P < 0.001). Adjusted mean monthly health care costs per patient were significantly higher among patients with recurrence vs patients without recurrence (differences of all-cause total costs, total medical costs, and pharmacy cost per month: $6,320, $4,924, and $1,387; all P < 0.001). CONCLUSIONS: RCC recurrence is associated with a significant increase in mortality, HRU, and health care costs, highlighting the substantial unmet need in patients with intermediate high-risk and high-risk RCC postnephrectomy when adjuvant therapies are not widely available. DISCLOSURES: Dr Sundaram is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in AbbVie, Abbott, Johnson & Johnson, Bristol Myers Squibb, and Merck & Co., Inc. Dr Bhattacharya is an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., and holds stock in Merck & Co., Inc. Dr Adejoro and Dr Rogerio were employees of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc. at the time of study conduct. Dr Adejoro holds stock in Johnson & Johnson. Dr Song, Dr Zhang, Mr Carley, and Dr Signorovitch are employees of Analysis Group, Inc., a consulting firm that received funding from Merck & Co., Inc. for the conduct of this research. Ms Zhu was an employee of Analysis Group, Inc. at the time of study conduct. Dr Haas is a Professor of Medicine at the Perelman School of Medicine, University of Pennsylvania and also serves on the advisory board for Aveo, Calithera and Exelixis, Co. Financial support for this study was provided by Merck & Co., Inc. The study sponsor was involved in the design and conduct of the study; collection, management, analysis, interpretation of data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

A Comparison of Home Health Utilization, Outcomes, and Cost Between Medicare Advantage and Traditional Medicare.

BACKGROUND: Home health use is rising rapidly in the United States as the population ages, the prevalence of chronic disease increases, and older Americans express their desire to age at home. Enrollment in Medicare Advantage (MA) plans rather than Traditional Medicare (TM) has grown as well, from 13% of total Medicare enrollment in 2004 to 39% in 2020. Despite these shifts, little is known about outcomes and costs following home health in MA as compared with TM. OBJECTIVE: The objective of this study was to measure the association of MA enrollment with outcomes and costs for patients using home health. DESIGN: This was a retrospective cohort study. PARTICIPANTS: Patients enrolled in plans offered by 1 large, national MA organization and patients enrolled in TM, with at least 1 home health visit between January 1, 2017, and June 30, 2018. EXPOSURE: MA enrollment. MAIN MEASURES: We compared the intensity of home health services and types of care delivered. The main outcome measures were hospitalization, the proportion of days in the home, and total allowed costs during the 180-day period following the first qualifying home health visit during the study period. KEY RESULTS: Among patients who used home health, our models demonstrated enrollment in MA was associated with 14%, and 6% decreased odds of 60- and 180-day hospitalization, respectively, a 12.8% and 14.7% decrease in medical costs exclusive and inclusive of home health costs, respectively, and a 0.27% increase in the proportion of days at home during the 180-day follow-up, equivalent to an additional half-day at home. There were few differences in home health care delivered for MA and TM [mean number of visits in the first episode of care (17.1 vs. 17.3) and mean visits per week (3.2 vs. 3.3)]. The mean number of visits by visit type and percent of patients with each type was similar between MA and TM as well. CONCLUSIONS: Compared with enrollment in TM, enrollment in MA was associated with improved patient-centered outcomes and lower cost and utilization, despite few differences in the way home health was delivered. These findings might be explained by structural components of MA that encourage better care management, but further investigation is needed to clarify the mechanisms by which MA enrollment may lead to higher value home health care.

Post-SNF outcomes and cost comparison: Medicare Advantage vs traditional Medicare.

OBJECTIVES: To compare outcomes and costs following skilled nursing facility (SNF) discharge for patients within a Medicare Advantage (MA) organization vs traditional Medicare (TM). STUDY DESIGN: Retrospective analysis of adults with a postacute SNF admission identified from MA claims (MA cohort: n = 56,228) and the Medicare 5% Limited Data Sets (TM cohort: n = 67,859). METHODS: Outcomes included hospitalization, proportion of days at home, and total medical costs during the 180 days post SNF discharge, and successful community discharge. Regression models accounted for patient characteristics and health care utilization in the 180 days prior to the proximal hospitalization and characteristics of the proximal hospitalization using backward variable selection and fixed effects for MA enrollment. To control for observable differences between individuals who selected MA vs TM, inverse probability of treatment weighting (IPTW) was conducted. RESULTS: The MA cohort was younger than the TM cohort (median age, 77 vs 81 years), more likely to have qualified for Medicare based on disability (29% vs 20%), and less likely to have dual Medicare/Medicaid eligibility (16% vs 23%). After adjustment, MA was associated with 22% decreased odds of hospitalization during the 180 days post SNF discharge, 19% increased odds of successful community discharge, a 4% increase in the proportion of days at home (equating to 6.7 additional days), and a 24% decrease in medical costs post SNF discharge. Results using IPTW were similar. CONCLUSIONS: MA was associated with better outcomes and lower costs post SNF discharge, suggesting efficiencies in care for SNF patients with MA. Further research is needed to evaluate specific MA features that may lead to better value.

Comparing Medical Utilization and Cost Outcomes in Oral Versus Injectable Immunotherapy Users with Chronic Inflammatory Joint and Skin Diseases.

BACKGROUND: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PSO) are immune-mediated systemic, chronic inflammatory conditions. Moderate to severe disease is treated with conventional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine, or leflunomide. If a patient does not respond to these firstline treatments, then tumor necrosis factor inhibitor (TNFi) or non-TNFi immunotherapy agents are administered via infusion, injection, or taken orally. Although the effectiveness of established infusion, injection, and newer oral therapies are known, the relative effectiveness among the routes of administration is not well understood. OBJECTIVE: To compare drug use, health care resource utilization, and costs among patients who are treatment-naive to oral immunotherapy and injectable biologic immunotherapy. METHODS: This retrospective observational study used claims data from a large U.S. health plan to identify new users of oral and injectable immunotherapy, diagnosed with a joint (RA or PsA), skin (PSO), or joint and skin condition from July 1, 2014, to June 30, 2017. The index date was the first claim for an oral or injectable medication. Medicaid, Medicare Advantage, and commercial plan patients aged 19-89 years with continuous enrollment 6 months before and 12 months after the index date were included in the study. Outcomes were adjusted using propensity score by inverse probability of treatment weighting. Treatment discontinuation, switching, health care resource utilization, and costs were measured during the post-index period. RESULTS: Oral versus injectable users with joint (n = 458 vs. 3,875), skin (n = 265 vs. 951), or joint and skin (n = 171 vs. 805) conditions were identified. For drug utilization outcomes, no differences in discontinuation rates were observed between oral and injectable groups for any of the cohorts. However, those in skin and joint and skin cohorts had higher rates of switching to other immunotherapies in patients initiated on orals compared with injectables. Health care resource utilization outcomes were mixed. While mean outpatient and physician office visits were significantly higher in oral compared with injectable groups across all 3 cohorts, no differences were observed for inpatient stays. Total costs (medical plus pharmacy) were lower for oral groups across all 3 cohorts. Pharmacy costs were lower for oral groups, but medical costs were higher for oral groups across all 3 cohorts. CONCLUSIONS: This is the first population-level study at a route-of-administration level, which compared switching, health care resource utilization, and costs across several conditions. Switching drugs was more likely in the oral group, which may indicate lower effectiveness or tolerability of oral immunotherapies relative to injectables. Health care resource utilization was higher in the oral group, but total costs were lower, which was likely driven by the lower costs of oral drugs. DISCLOSURES: This study was a Humana internal study, and all authors were at the time employees of Humana and used Humana resources. The authors have no conflicts of interest or financial interests to disclose that relate to the research described in this study. This study was presented as a podium and poster presentation at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Amyotrophic lateral sclerosis among patients with a Medicare Advantage prescription drug plan; prevalence, survival and patient characteristics.

Objective: To estimate amyotrophic lateral sclerosis (ALS) prevalence, 5-year survival, and explore factors associated with survival in a Medicare population. Methods: A validated administrative claims algorithm was used to classify individual's ages 18-89 years at index date (first claim with a diagnosis of motor neuron disease or ALS between 1 January 2007 and 31 December 2011) with Medicare Advantage prescription drug coverage into mutually exclusive categories: ALS, no ALS, and possible ALS. Crude prevalence and cumulative survival from index date to the date of death, disenrollment or end of the study were calculated. Cox-proportional hazards were used to estimate and explore factors associated with survival. Results: Of 2631 eligible individuals, the algorithm identified 1271 (48 %), 1157 (44 %), 203 (8 %) as ALS, no ALS and possible ALS, respectively. The 5-year period prevalence and the 2011 point prevalence of ALS were 20.5 and 11.8 per 100,000, respectively. Evidence of death was documented in 81%, 35%, and 1.6% of the ALS, no ALS or possible ALS groups, respectively. Unadjusted median survival time was 388, 542 and 1473 days for the ALS, no ALS and possible ALS groups, respectively. Seeing a psychiatrist or neurologist at the index visit, having respiratory or genitourinary comorbidities, and the number of pre-index acute inpatient admissions were associated with shorter survival. Conclusions: Surveillance data from a Medicare population demonstrated a higher prevalence of ALS. Results highlight the need for effective ALS treatment options and resources for patients with ALS who will likely face limited therapeutic choices and care options at the end of life.

Depression treatment decreases healthcare expenditures among working age patients with comorbid conditions and type 2 diabetes mellitus along with newly-diagnosed depression.

BACKGROUND: There are many studies in the literature on the association between depression treatment and health expenditures. However, there is a knowledge gap in examining this relationship taking into account coexisting chronic conditions among patients with diabetes. We aim to analyze the association between depression treatment and healthcare expenditures among adults with Type 2 Diabetes Mellitus (T2DM) and newly-diagnosed depression, with consideration of coexisting chronic physical conditions. METHODS: We used multi-state Medicaid data (2000-2008) and adopted a retrospective longitudinal cohort design. Medical conditions were identified using diagnosis codes (ICD-9-CM and CPT systems). Healthcare expenditures were aggregated for each month for 12 months. Types of coexisting chronic physical conditions were hierarchically grouped into: dominant, concordant, discordant, and both concordant and discordant. Depression treatment categories were as follows: antidepressants or psychotherapy, both antidepressants and psychotherapy, and no treatment. We used linear mixed-effects models on log-transformed expenditures (total and T2DM-related) to examine the relationship between depression treatment and health expenditures. The analyses were conducted on the overall study population and also on subgroups that had coexisting chronic physical conditions. RESULTS: Total healthcare expenditures were reduced by treatment with antidepressants (16 % reduction), psychotherapy (22 %), and both therapy types in combination (28 %) compared to no depression treatment. Treatment with both antidepressants and psychotherapy was associated with reductions in total healthcare expenditures among all groups that had a coexisting chronic physical condition. CONCLUSIONS: Among adults with T2DM and chronic conditions, treatment with both antidepressants and psychotherapy may result in economic benefits.

A Real-World Observational Study of Time to Treatment Intensification Among Elderly Patients with Inadequately Controlled Type 2 Diabetes Mellitus.

BACKGROUND: Among elderly patients, the management of type 2 diabetes mellitus (T2DM) is complicated by population heterogeneity and elderly-specific complexities. Few studies have been done to understand treatment intensification among elderly patients failing multiple oral antidiabetic drugs (OADs). OBJECTIVE: To examine the association between time to treatment intensification of T2DM and elderly-specific patient complexities. METHODS: In this observational, retrospective cohort study, elderly (aged ≥ 65 years) Medicare beneficiaries (n = 16,653) with inadequately controlled T2DM (hemoglobin A1c ≥ 8.0% despite 2 OADs) were included. Based on the consensus statement for diabetes care in elderly patients published by the American Diabetes Association and the American Geriatric Society, elderly-specific patient complexities were defined as the presence or absence of 5 geriatric syndromes: cognitive impairment; depression; falls and fall risk; polypharmacy; and urinary incontinence. RESULTS: Overall, 48.7% of patients received intensified treatment during follow-up, with median time to intensification 18.5 months (95% CI = 17.7-19.3). Median time to treatment intensification was shorter for elderly patients with T2DM with polypharmacy (16.5 months) and falls and fall risk (12.7 months) versus those without polypharmacy (20.4 months) and no fall risk (18.6 months). Elderly patients with urinary incontinence had a longer median time to treatment intensification (18.6 months) versus those without urinary incontinence (14.6 months). The median time to treatment intensification did not significantly differ by the elderly-specific patient complexities that included cognitive impairment and depression. However, after adjusting for demographic, insurance, clinical characteristics, and health care utilization, we found that only polypharmacy was associated with time to treatment intensification (adjusted hazard ratio, 1.10; 95% CI = 1.04-1.15; P = 0.001). CONCLUSIONS: Less than half of elderly patients with inadequately controlled T2DM received treatment intensification. Elderly-specific patient complexities were not associated with time to treatment intensification, emphasizing a positive effect of the integrated health care delivery model. Emerging health care delivery models that target integrated care may be crucial in providing appropriate treatment for elderly T2DM patients with complex conditions.

A real-world study of the effect of timing of insulin initiation on outcomes in older medicare beneficiaries with type 2 diabetes mellitus.

OBJECTIVES: To compare clinical and economic outcomes of early insulin initiation with those of delayed initiation in older adults with type 2 diabetes mellitus (T2DM). DESIGN: Retrospective cohort study. SETTING: Humana Medicare Advantage health insurance plan. PARTICIPANTS: Older (≥65) Medicare beneficiaries with T2DM. MEASUREMENTS: Subjects were grouped according to number of classes of oral antidiabetes drugs (OADs) they had taken before initiation of insulin: one (early insulin initiators), two, or three or more (delayed insulin initiators). One-year follow-up outcomes included change in glycosylated hemoglobin (HbA1c), percentage of older adults with HbA1c less than 8.0%, hypoglycemic events, and total healthcare costs. RESULTS: Overall, 14,669 individuals were included in the analysis. Baseline and 1-year follow-up HbA1c levels were available for 4,028 (27.5%) individuals. Insulin was initiated early in 32% and delayed in 20%. At follow-up, unadjusted reduction in HbA1c was 0.9±3.7% for the group with one OAD, 0.7±2.4% for those with two, and 0.5±3.6% for those with three or more. Early insulin initiation was associated with significantly greater reduction in HbA1c (0.4%; adjusted P<.001), 30% greater likelihood of achieving HbA1c less than 8.0% (adjusted odds ratio=1.30, 95% confidence interval=1.18-1.43), and no significant differences in total costs or hypoglycemia events (11.5% of early initiators vs 10.2% of delayed initiators; P=.32). CONCLUSION: This study suggests beneficial effects of early insulin initiation in older adults with T2DM who do not have adequate glycemic control, without increasing the risk of hypoglycemia or greater total direct healthcare costs.

Depression and ambulatory care sensitive hospitalizations among Medicare beneficiaries with chronic physical conditions.

OBJECTIVE: We examined the association between depression and hospitalizations for Ambulatory Care Sensitive Conditions (H-ACSC) among Medicare beneficiaries with chronic physical conditions. METHODS: We used a retrospective longitudinal design using multiple years (2002-2009) of linked fee-for-service Medicare claims and survey data from Medicare Current Beneficiary Survey to create six longitudinal panels. We followed individuals in each panel for a period of 3-years; first year served as the baseline and subsequent 2-years served as the follow-up. We measured depression, chronic physical conditions and other characteristics at baseline and examined H-ACSC at follow-up. We identified chronic physical conditions from survey data and H-ACSC and depression from fee-for-service Medicare claims. We analyzed unadjusted and adjusted relationships between depression and the risk of H-ACSC with chi-square tests and logistic regressions. RESULTS: Among all Medicare beneficiaries, 9.3% had diagnosed depression. Medicare beneficiaries with depression had higher rates of any H-ACSC as compared to those without depression (13.6% vs. 7.7%). Multivariable regression indicated that, compared to those without depression, Medicare beneficiaries with depression were more likely to experience any H-ACSC. CONCLUSIONS: Depression was associated with greater risk of H-ACSC, suggesting that health care quality measures may need to include depression as a risk-adjustment variable.