Burden of renal angiomyolipomas associated with tuberous sclerosis complex: results of a patient and caregiver survey.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors in multiple organs, including non-cancerous kidney lesions known as renal angiomyolipomas. This study's objective is to describe the age-stratified morbidity, treatment patterns, and health-related quality of life of TSC patients with renal angiomyolipomas in the United States. A cross-sectional, anonymous web-based survey was conducted with a convenience sample of TSC patients and caregivers identified through a patient advocacy organization. RESULTS: Out of the total sample of 676, 182 respondents reported having kidney complications with 33% of the pediatric group and 25% of the adult group with TSC reporting them. Of those with kidney complications, 110 (60%) reported a diagnosis of renal angiomyolipomas, of which 79 (72%) were adult patients and 31 (28%) were pediatric age patients. Eighty-four percent of the pediatric group and 76% of the adult group reported lesions on both kidneys. Of the patients experiencing involvement of only one kidney, 60% of the pediatric group and 21% of the adult group reported having multiple tumors within the affected kidney. Almost all of the sample (99%) reported seeing a physician and having a procedure or test for TSC in the past year. Less than half the respondents (44%) reported being hospitalized in the past year. Thirty-nine percent reported an emergency room visit as well. Compared to scores for patients with kidney disease, the angiomyolipoma adult patients reported significantly lower Mental Component Summary scores on the SF-12. CONCLUSIONS: Renal angiomyolipomas burden leads to frequent healthcare resource use including hospitalization, invasive treatments, and surgical procedures, which result in an impaired mental health related quality of life.

Management of a Rare Disease Population: A Model for Identifying a Patient Population With Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a rare genetic disorder affecting the brain and other vital organs with varying symptoms and severity among patients. This study developed and validated a risk model to identify patients with TSC using large databases of medical and pharmacy claims.

Patterns of Disease Monitoring and Treatment Among Patients With Tuberous Sclerosis Complex-related Angiomyolipomas.

OBJECTIVE: To use the tuberous sclerosis complex (TSC) Natural History Database to describe monitoring and treatment patterns among patients with TSC-related angiomyolipomas (AMLs). METHODS: This study used the TSC Natural History Database, which contains demographics, affected areas, diagnosis, and treatments for more than 1300 patients with TSC enrolled in 16 participating clinics during 2006-2013. Patient characteristics, AML monitoring tests, and AML treatments were assessed. RESULTS: Among the 621 patients with TSC-related AMLs, 54% were female; 77% were Caucasian. Median age at TSC diagnosis was <1 year, whereas median age at AML diagnosis was 9.8 years. Most patients (84%) had at least 1 monitoring test following AML diagnosis. The most commonly used tests were magnetic resonance imaging (MRI; 65% of patients), ultrasound (62%), and computed tomography (41%). Between 2000 and 2012, MRI made up an increasingly large proportion of the total number of monitoring tests. Once diagnosed, 155 (25%) of patients received treatment for AML. The median time from diagnosis to first treatment was 3.8 years. The most common treatments were embolization (10%), everolimus (9%), sirolimus (6%), and nephrectomy (6%). The rate of nephrectomies declined over time, with none conducted during 2011 and 2012. No subsequent surgeries were reported among the 71 patients who received mTOR inhibitor as first-line therapy. CONCLUSION: The use of MRIs increased between 2000 and 2012 among patients with TSC-AML. The majority of these patients did not receive treatment for AML. Use of nephrectomy decreased over the study period and was particularly rare in patients who received an mTOR inhibitor.

Natural history of patients with tuberous sclerosis complex related renal angiomyolipoma.

OBJECTIVE: To examine temporal relationships between tuberous sclerosis complex (TSC) and renal angiomyolipoma diagnosis and outcomes, treatment, and healthcare utilization. METHODS: Administrative data from the MarketScan Commercial Database was used to select TSC-related renal angiomyolipoma patients during 1 January 2000-31 March 2013. Patients were followed until the earliest of inpatient death or end of enrollment or study. Occurrence of kidney-related outcomes, kidney-related procedures, and all-cause healthcare utilization and time to occurrence were reported. Kaplan-Meier curves were used to display the unadjusted distribution of time to outcome. RESULTS: A total of 605 patients were selected (<18 years N = 225; ≥18 years N = 380). Mean time from TSC to renal angiomyolipoma diagnosis was 25.7 months in younger and 16.9 months in older patients. Patients ≥18 years had higher rates of chronic kidney disease (CKD), hematuria, kidney failure, embolization (EMB), and partial and complete nephrectomy compared to patients <18 years (all p < .05). Mean time from TSC-related renal angiomyolipoma diagnosis to CKD, hematuria, kidney failure, EMB, first emergency room and inpatient visits was shorter in older compared to younger patients (all p < .05). Probability of developing CKD was approximately 0.8 and 0.95 within 3 years in younger and older patients, respectively. CONCLUSIONS: Patients with TSC-related renal angiomyolipoma had high rates of kidney-related outcomes and procedures. These events sometimes preceded the angiomyolipoma diagnosis. A key study limitation was that due to the small sample size, results may have been biased by outliers. Research is needed to determine whether earlier angiomyolipoma diagnosis can impact occurrence of events and reduce healthcare utilization.

Healthcare utilization and costs in patients with tuberous sclerosiscomplex-related renal angiomyolipoma.

OBJECTIVE: To quantify healthcare utilization and costs in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma (AML) in a matched cohort of patients without TSC or AML. METHODS: Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML during January 1, 2000-March 31, 2013 from the Commercial database and January 1, 2000-June 30, 2012 from the Medicaid database. Patients were required to have at least 30 days of follow-up from initiation into the study, and were followed until inpatient death, end of insurance coverage, or the end of study. Age, calendar year, and payer-matched controls that had no TSC and no AML were selected. All-cause annualized healthcare utilization and costs were calculated by service category. RESULTS: A total of 218 patients under 18 years and 377 patients 18 years and older with TSC-renal AML were selected from the Commercial database, and matched to 654 and 1,131 controls, respectively. Thirty-eight patients under 18 years and 110 patients 18 years or older with TSC-renal AML were selected from the Medicaid database, and matched to 54 and 212 controls, respectively. Within the Commercial cohort, and across both age groups, TSC-renal AML patients utilized more healthcare services than their matched controls. Within the Medicaid cohort, in both age groups, utilization was higher in TSC-renal AML patients vs control patients for inpatient admissions, emergency room visits, physician office visits, and hospital-based outpatient visits. Across age groups and in both the Commercial and Medicaid cohorts, the annual average total costs were significantly higher in TSC-renal AML patients compared to control patients (p < 0.05 for all). Healthcare costs ranged from $29,240-$48,499 for TSC-renal AML patients and from $2,082-$10,864 for control patients. CONCLUSIONS: Compared to controls, TSC-renal AML patients incurred substantially higher annual healthcare utilization and costs.

Long-term Clinical Morbidity in Patients With Renal Angiomyolipoma Associated With Tuberous Sclerosis Complex.

OBJECTIVE: To estimate the incidence rates of kidney-related clinical outcomes among patients with tuberous sclerosis complex (TSC)-related angiomyolipoma (AML) compared to an age-matched control cohort in the United States. MATERIALS AND METHODS: This was a retrospective, observational study. Administrative data from the MarketScan Research Databases were used to select patients with TSC and renal AML. An age-matched group with no TSC or renal AML was identified for comparison. Outcomes were incidence rates per 100 patient-years and number of months to development of hematuria, chronic kidney disease, renal hemorrhage, kidney failure, and inpatient death. RESULTS: Among the commercially insured TSC-renal AML patients (N = 605) and matched controls (N = 1815), 37.2% were <18 years old. Among Medicaid TSC-renal AML patients (N = 246) and matched controls (N = 738), 38.6% were aged <18. In the commercial sample, in both age groups (<18 and ≥18), the incidence rate of each clinical outcome measured was higher in the TSC-renal AML cohort than in the control cohort, with several differences reaching statistical significance. Compared with younger patients, older TSC-renal AML patients had higher incidence rates of clinical outcomes (hematuria: 20.4 vs 8.7; chronic kidney disease: 9.6 vs 3.5; renal hemorrhage 2.7 vs 0.7; kidney failure: 1.9 vs 0.4) and took less time on average to develop each clinical outcome. A similar pattern of results was observed among patients with Medicaid insurance. CONCLUSION: TSC-renal AML patients are at significantly higher risk for renal morbidity relative to the general population.

Rates of interventional procedures in patients with tuberous sclerosis complex-related renal angiomyolipoma.

OBJECTIVE: To describe rates of renal artery embolization, partial nephrectomy, and complete nephrectomy in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma. METHODS: Data from the MarketScan® Research Databases were used to select patients with TSC and renal angiomyolipoma during January 1, 2000-March 31,2013 (Commercial database) and January 1, 2000-June 30, 2012 (Medicaid database). Patients had at least 30 days of follow-up and were followed until the earliest of inpatient death, end of enrollment, or end of study. Rates of embolization and nephrectomy were calculated. RESULTS: In total, 218 patients <18 years (mean = 9.7 years) and 378 patients ≥18 years (mean 36.9 years) were selected from the Commercial database. Fifty-nine patients <18 years (mean = 7.2 years) and 117 patients ≥18 years (mean = 37.2 years) were selected from the Medicaid database. Follow-up in the Medicaid cohorts was approximately twice that of the Commercial cohorts. Among patients in the study, 24.2% had at least one interventional procedure: 15.2% had embolization, 5.2% had partial nephrectomy, and 7.6% had complete nephrectomy. Within the Commercial cohort ≥18 years, 18.5% had embolization, 7.7% had partial nephrectomy, and 11.4% had complete nephrectomy. Corresponding percentages in the Medicaid adult cohort were 17.1%, 5.1%, and 4.3%. Repeat embolization procedures occurred in up to 7.7% of Commercial patients and in up to 6.8% of Medicaid patients. Repeat partial nephrectomy occurred in up to 4.5% and 1.7% of Commercial and Medicaid patients, respectively. CONCLUSIONS: Approximately 25% of patients with TSC-renal angiomyolipoma experienced embolization or nephrectomy, with some patients undergoing repeat procedures. Study limitations included small sample sizes, the majority of the study period occurred prior to the approval of mammalian target of rapamycin inhibitors for the treatment of TSC-renal AML, and results may not be generalizable to patients with insurance other than commercial or Medicaid.

Caring for Children With Tuberous Sclerosis Complex: What Is the Physical and Mental Health Impact on Caregivers?

Disease burden associated with tuberous sclerosis complex, a genetic disorder characterized by benign tumor growth including lesions in multiple organs, puts tremendous demands on families. This analysis examines the physical and mental health burden of tuberous sclerosis complex caregivers in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex caregivers collected information; descriptive analyses were conducted on age-based subgroups. A total of 275 caregivers of tuberous sclerosis complex patients responded. Mean patient age ≤ 18 years was 6.9 (±4.4) and 42.3 (±18.2) for patients >18 years of age. Caregivers reported multiple tuberous sclerosis complex manifestations and high health care utilization for patients. Caregivers spending more time on doctor visits or researching tuberous sclerosis complex had lower physical and mental health-related quality of life scores and more depressive symptoms. Tuberous sclerosis complex caregivers had significantly lower physical and mental health-related quality of life scores and more depressive symptomatology compared to US healthy adult population norms.

Tuberous sclerosis complex: a survey of health care resource use and health burden.

PURPOSE: Tuberous sclerosis complex (TSC) is a multiorgan, autosomal-dominant genetic disorder with incomplete penetrance. METHODS: This analysis of a web-based survey focuses on the clinical presentation, management, and associated burden of patients with TSC in the United States. RESULTS: A total of 676 TSC patients or caregivers responded. Both pediatric and adult patient groups experienced skin lesions (77% and 44%), seizures (77% and 24%), and kidney complications (33% and 25%) as well as other manifestations. Patient groups averaged 22 visits to a physician, nine procedures/tests, two emergency room visits, and two hospital admissions in the past year. Standardized tests were administered for health-related quality of life and TSC patients reported significantly worse mental health scores and better physical health scores compared to a normative sample of cancer patients. CONCLUSION: Results demonstrate that TSC is associated with significant clinical burden, resource utilization, and decreased mental health well-being.

The burden of subependymal giant cell astrocytomas associated with tuberous sclerosis complex: results of a patient and caregiver survey.

Tuberous sclerosis complex is a genetic disorder characterized by benign tumor growth including lesions in the ventricular system of the brain known as subependymal giant cell astrocytomas. This analysis focuses on the clinical presentation, management, and associated burden of subependymal giant cell astrocytomas in patients with tuberous sclerosis complex in the United States. An institutional review board-approved web-based survey of tuberous sclerosis complex patients and caregivers collected information, and descriptive analyses were conducted on age-based subgroups. A total of 116 tuberous sclerosis complex-subependymal giant cell astrocytoma patients or caregivers responded (17% of the total tuberous sclerosis complex sample). Mean and median patient ages were 25.5 and 23.5 years. Besides subependymal giant cell astrocytomas, patients also experienced skin lesions (72%), seizures (65%), and cognitive concerns (60%). Forty-five percent reported having brain surgery (22% for subependymal giant cell astrocytoma). In the past year, 42% of patients were admitted at least once to the hospital whereas 39% went to the emergency department. Results demonstrate that tuberous sclerosis complex-subependymal giant cell astrocytoma is associated with significant clinical burden, resource utilization, and decreased well-being.