Epidemiology and economic burden of Von Hippel-Lindau Disease-associated central nervous system hemangioblastomas and pancreatic neuroendocrine tumors in the United States.

BACKGROUND: To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau-associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US). METHODS: Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum's de-identified Clinformatics® Data Mart Database (2007-2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts. RESULTS: In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high. CONCLUSIONS: In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery-related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease.

Epidemiology and Economic Burden of von Hippel-Lindau Disease-Associated Renal Cell Carcinoma in the United States.

INTRODUCTION: We developed a claims-based algorithm to identify patients with von Hippel-Lindau disease-associated renal cell carcinoma (VHL-RCC) from a real-world database and quantified the prevalence, healthcare resource utilization (HRU), and healthcare costs of VHL-RCC in the United States (US). METHODS: Using data from the Optum Clinformatics Data Mart (2007-2020), an algorithm was developed to identify patients with VHL-RCC, who were matched to controls without VHL disease or RCC. VHL-RCC prevalence in 2019 was estimated and standardized to the US population. HRU and costs were compared between patients with VHL-RCC versus controls, and costs associated with tumor reduction procedures were estimated among patients with VHL-RCC. All costs were adjusted to 2020 US dollars. RESULTS: VHL-RCC prevalence in the US was 0.92 per 100,000 persons, resulting in 3023 estimated patients with VHL-RCC in the US. The VHL-RCC cohort (N = 160) incurred higher rates of inpatient, outpatient, and emergency department visits versus controls (N = 800), translating to $36,450 more in adjusted all-cause annual healthcare costs. By examining only claims with an associated RCC diagnosis, it was estimated that patients with VHL-RCC incurred $21,123 annually in healthcare costs due to RCC management, and the average cost of nephrectomy was $29,313. Among different complications of RCC-related tumor reduction procedures, end-stage renal disease was the costliest, which incurred $65,338 over 6 months postnephrectomy. CONCLUSION: VHL-RCC was associated with significant HRU and healthcare costs, including those related to tumor surgeries. This study underscores the importance of novel therapies that can reduce the clinical burden and medical intervention costs of VHL-RCC.

Functional and Clinical Outcomes Associated with Steroid Treatment among Non-ambulatory Patients with Duchenne Muscular Dystrophy1.

BACKGROUND: Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited. OBJECTIVE: Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD. METHODS: Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models. RESULTS: This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids). CONCLUSIONS: Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.

The Economic Burden of Recurrence in Triple-Negative Breast Cancer Among Working Age Patients in the United States.

INTRODUCTION: Triple-negative breast cancer (TNBC) is associated with a high recurrence risk. However, the magnitude of direct and indirect costs associated with recurrence is lacking in the literature. METHODS: Adults 18-65 years old diagnosed with TNBC were identified from the OptumHealth Reporting and Insights claims database (1999-2017) and stratified by recurrence. For patients with recurrence, the index date was defined as 30 days before recurrence; for patients without recurrence, it was randomly assigned based on the distribution of time between first treatments and index dates of the recurrence cohort. All-cause and breast cancer-related healthcare resource utilization (HRU), direct and indirect costs, and work loss up to 1 year were compared between cohorts using generalized linear models. Kaplan-Meier analyses and Cox proportional hazards models compared the risk of leaving the workforce. RESULTS: Among the 2340 patients analyzed, mean age was 54 years and > 75% of patients had stage 0-2 cancer. Among the 1170 patients with recurrence, 236 were categorized as having metastatic recurrence and 934 as having locoregional recurrence. Relative to patients without recurrence, those with recurrence had significantly higher all-cause and breast cancer-related HRU. For instance, adjusted incidence rates (IRs) for all-cause inpatient admissions were 3.67 and 10.19 times higher for patients with locoregional and metastatic recurrence, respectively (p < 0.001). Adjusted all-cause healthcare costs were $8575/month higher for metastatic recurrence and $3609/month higher for locoregional recurrence vs. patients without recurrence (p < 0.001). Adjusted IRs for work loss days were approximately two times higher for locoregional and metastatic recurrence vs. without recurrence (p < 0.001). Patients with locoregional recurrence incurred $335/month more indirect costs vs. patients without recurrence; those with metastatic recurrence incurred $769/month more (p < 0.05). Patients with recurrence had a 63% higher rate of leaving the work force (p = 0.003). CONCLUSION: The incremental direct and indirect economic burden associated with recurrent TNBC is substantial relative to non-recurrence.

Impact of PASI response on work productivity and the effect of risankizumab on indirect costs using machine learning in patients with moderate-to-severe psoriasis.

OBJECTIVES: To compare the impact of Psoriasis Area and Severity Index (PASI) response on total work productivity impairment (TWPI) in patients with moderate-to-severe psoriasis; to compare TWPI and associated indirect costs among patients treated with risankizumab, adalimumab, ustekinumab, and placebo. METHODS: Data from REVEAL (adalimumab phase III trial) were used to assess differences in trial-observed TWPI across PASI response cohorts. A machine learning model used REVEAL data to predict TWPI for patients in the risankizumab trials. These values were used to estimate work loss hours and work impairment-related indirect costs for each treatment cohort. RESULTS: Among REVEAL patients (N = 741), TWPI in the PASI 100, 90-99, 75-89 cohorts was lower than the PASI <75 cohort (p < .05); mean TWPI was lowest with PASI 100 (1.7%) vs. 90-99 (2.5%) vs. 75-89 (4.8%) vs. <75 (14.3%). There was a significant (p < .0001) monotonic relationship between higher PASI response and lower TWPI. In the risankizumab trials (N = 2046), incremental TWPI relative to risankizumab was 3.4%/week for ustekinumab/adalimumab, and 17.1%/week for placebo; incremental indirect cost savings for risankizumab were $2179/year vs. adalimumab, $2321/year vs. ustekinumab, and $11,284/year vs. placebo. CONCLUSIONS: Higher PASI responses were associated with reduced TWPI. Risankizumab was associated with less work impairment/indirect costs vs. ustekinumab/adalimumab/placebo.

Post-transplant maintenance therapy in patients with FLT3-mutated acute myeloid leukemia: Real-world treatment patterns and outcomes.

OBJECTIVES: Maintenance therapy is one strategy to prolong survival in patients with acute myeloid leukemia (AML) following hematopoietic stem cell transplantation (HSCT). We evaluated real-world treatment patterns and outcomes in patients with newly diagnosed FLT3-mutated AML receiving HSCT after complete remission with first-line chemotherapy. METHODS: A global, retrospective chart review to evaluate maintenance therapy and outcomes in patients with FLT3-mutated AML after HSCT. RESULTS: Data from 1208 charts from eight countries showed that most patients (n = 765 [63.3%]) received no maintenance therapy after HSCT, 219 (18.1%) received FLT3 inhibitor maintenance therapy, and 224 (18.5%) received other types of maintenance therapy. No systematic differences were observed in healthcare resource utilization across the three groups. Clinical benefit was observed with FLT3 inhibitor maintenance over no maintenance therapy with relapse-free survival (adjusted hazard ratio [HR] 0.57 [95% CI 0.34-0.94], P < .05). FLT3 inhibitor and other maintenance also demonstrated overall survival benefit over no maintenance (adjusted HR 0.50 [95% CI 0.28-0.89] and 0.46 [95% CI 0.23-0.91], respectively; both P < .05). CONCLUSIONS: Real-world maintenance therapies after HSCT in patients with FLT3-mutated AML were heterogeneous. While overall use of healthcare resources was not significantly increased in patients receiving maintenance therapy versus those who did not, clinical outcomes were improved.

A Longitudinal Assessment of the Impact of Endometriosis on Patients' Salary Growth and Risk of Leaving the Workforce.

INTRODUCTION: This retrospective cohort study evaluated the impact of endometriosis on the risks of work loss events and salary/growth over a 5-year period. METHODS: Women aged 18-49 years with ≥ 1 endometriosis diagnosis were identified in a claims database and matched 1:1 to women without endometriosis (controls). The index date was the first endometriosis diagnosis date (endometriosis cohort) or a random date during the period of continuous eligibility (controls). Baseline characteristics were compared between cohorts descriptively. Average annual salaries were compared over the 5 years post-index using generalized estimating equations accounting for matching. Time-to-event analyses assessed risk of short-term disability, long-term disability, leave of absence, early retirement, and any event of leaving the workforce (Kaplan-Meier curves with log-rank tests). RESULTS: A total of 6851 matched pairs (mean age at index date: 38.7 years) were included in the salary growth analysis, with a subset of 1981 pairs in the risk of leaving the workforce analysis. In year 1, the endometriosis cohort had a lower average annual salary ($61,322) than controls ($64,720); salaries were lower in years 2-5 by $3697-$6600 (all p < 0.01). The endometriosis cohort experienced smaller salary growth than controls in all years, ranging from $438 vs. $1058 in year 1 to $4906 vs. $7074 in year 5 (all p < 0.05). In the Kaplan-Meier analyses, patients with endometriosis were significantly more likely than controls to leave the workforce for any reason, take a leave of absence, and use short-term disability (all log-rank tests p < 0.001). Additionally, the median number of years to each of these events was lower for the endometriosis cohort relative to the matched controls. Sensitivity analyses among patients with moderate-to-severe endometriosis and by salary brackets confirmed the primary analyses. CONCLUSIONS: Patients with endometriosis experienced lower annual salary and salary growth, as well as higher risks of work loss events, compared with matched controls.

Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center.

Aim: To assess outcomes among patients with Duchenne muscular dystrophy receiving deflazacort or prednisone in real-world practice. Methods: Clinical data for 435 boys with Duchenne muscular dystrophy from Cincinnati Children's Hospital Medical Center were studied retrospectively using time-to-event and regression analyses. Results: Median ages at loss of ambulation were 15.6 and 13.5 years among deflazacort- and prednisone-initiated patients, respectively. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration. No differences were observed in whole body bone mineral density or left ventricular ejection fraction. Conclusion: This single center study adds to the real-world evidence associating deflazacort with improved clinical outcomes.