Treatment patterns and costs among biologic-naive patients initiating apremilast or biologics for psoriatic arthritis.

Aim: We evaluated treatment patterns and healthcare costs of initiating psoriatic arthritis (PsA) treatment with oral apremilast versus biologics. Methods: Claims data identified biologic-naive adults with PsA who initiated either apremilast or a biologic from 2013 to 2016. Results: Medication adherence was similar at 12 months (76.9 vs 73.4%; p = 0.175) between apremilast (n = 381) and matched biologic (n = 761) patients. Apremilast users had $12,715 lower total costs per-patient-per-month (p < 0.001), largely due to outpatient pharmacy and medical costs. Conclusion: Commercially insured patients with PsA initiating apremilast had adherence similar to those initiating biologics but lower total healthcare costs.

Comparison of treatment patterns, resource utilization, and cost of care in patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel plus gemcitabine or FOLFIRINOX.

BACKGROUND: We compared real-world treatment patterns, resource utilization, and cost of care for patients with metastatic pancreatic cancer treated with first-line nab-paclitaxel + gemcitabine or FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, oxaliplatin). METHODS: This was a retrospective study of inpatient and hospital-based outpatient data in the United States. Primary endpoints included median time to treatment discontinuation (TTD) and total cost of care per patient per month. Secondary endpoints included supportive care costs and hospitalization rate and length. RESULTS: Overall, 345 patients were included (nab-paclitaxel + gemcitabine, n = 182; FOLFIRINOX, n = 163). Median TTD was significantly longer with nab-paclitaxel + gemcitabine vs FOLFIRINOX (4.3 vs 2.8 months; P = .0009). Mean acquisition cost was higher with nab-paclitaxel + gemcitabine ($10,643 vs $6549; P = .0043), but mean total cost of care was lower ($16,628 vs $19,936; P = .1740). Supportive care cost was significantly lower with nab-paclitaxel + gemcitabine ($1995 vs $6456; P < .0001). Hospitalization rate and length were both significantly lower with nab-paclitaxel + gemcitabine. CONCLUSIONS: Despite higher acquisition costs with nab-paclitaxel + gemcitabine, FOLFIRINOX-treated patients had higher total costs driven by supportive care. Toxicity-related costs and drug acquisition costs should be considered when evaluating total cost of care.

Treatment patterns, health state, and health care resource utilization of patients with radioactive iodine refractory differentiated thyroid cancer.

BACKGROUND: Patients with differentiated thyroid cancer (DTC) often respond well to treatment but some become refractory to radioactive iodine (RAI) treatment, and treatment options are limited. Despite the humanistic and economic burden RAI refractory disease imposes on patients, published research concerning treatment patterns and health care resource utilization is sparse. METHODS: Data were collected from an online retrospective chart review study in the US and five European Union (EU) countries (France, Germany, Italy, Spain, and UK) with physicians recruited from an online panel. Physicians (N=211) provided demographics, disease history, treatment information, and health care resource utilization for one to four of their patients with radioactive iodine refractory differentiated thyroid cancer (RR-DTC). RESULTS: The majority of the patients with RR-DTC (N=623) were female (56%), and their mean age was 58.2 years. In this sample, 63.2% had papillary thyroid cancer and 57.0% were in Stage IV when deemed RAI refractory. Patients with RR-DTC experienced regional recurrence in the thyroid bed/central neck area (25.3%) and had distant metastatic disease (53.6%). At the time data were collected, 50.7% were receiving systemic treatment. Of those, 78.5% were on first-line treatment and 62.7% were receiving multikinase inhibitors. Regional differences for prescribed treatments were observed; the US was more likely to have patients receiving multikinase inhibitors (79.2%) compared with UK (41.2%) and Italy (17.1%). Additional details regarding treatment patterns and resource utilization are discussed. CONCLUSION: The current study aimed to obtain a greater understanding of RR-DTC treatment globally. These results can assist in the development and implementation of treatment guidelines and ultimately enhance the care of patients with RR-DTC.

Health state utility valuation in radioactive iodine-refractory differentiated thyroid cancer.

PURPOSE: The aim of this study was to elicit utilities for radioactive iodine-refractory differentiated thyroid cancer (RR-DTC) and evaluate the impact of treatment response and toxicities on quality of life. PATIENTS AND METHODS: RR-DTC health states were developed based on data from a previous qualitative study and iterative review by clinical experts. Following piloting, health states underwent valuation by 100 members of the UK public during time trade-off interviews. Mean utilities and descriptive distribution statistics were calculated, and a logistic regression analysis was conducted. RESULTS: The demographic characteristics of the study sample were generally reflective of the UK population. Clear differentiation in valuation between health states was observed. No response/stable disease had an adjusted utility value of 0.87, with a corresponding gain of +0.04 following a treatment response and a decline of -0.35 for disease progression. Adverse events were associated with utility decrements between -0.47 (grade III diarrhea) and -0.05 (grade I/II alopecia). CONCLUSION: The trade-off interviews derived utility weights show clear differentiation between RR-DTC health states in response to treatment. The values reported in this study are suitable for cost-effectiveness evaluations for new treatments in RR-DTC.

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.

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.

Nucleophosmin mediates mammalian target of rapamycin-dependent actin cytoskeleton dynamics and proliferation in neurofibromin-deficient astrocytes.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant tumor predisposition syndrome in which affected individuals develop astrocytic brain tumors (gliomas). To determine how the NF1 gene product (neurofibromin) regulates astrocyte growth and motility relevant to glioma formation, we have used Nf1-deficient primary murine astrocytes. Nf1(-/-) astrocytes exhibit increased protein translation and cell proliferation, which are mediated by Ras-dependent hyperactivation of the mammalian target of rapamycin (mTOR) protein, a serine/threonine protein kinase that regulates ribosomal biogenesis, protein translation, actin cytoskeleton dynamics, and cell proliferation. In this study, we show that Nf1-deficient astrocytes have fewer actin stress fibers and exhibit increased cell motility compared with wild-type astrocytes, which are rescued by pharmacologic and genetic mTOR inhibition. We further show that mTOR-dependent regulation of actin stress fiber formation, motility, and proliferation requires rapamycin-sensitive activation of the Rac1 GTPase but not elongation factor 4E-binding protein 1/S6 kinase. Nf1(-/-) astrocytes also exhibit increased protein translation and ribosomal biogenesis through increased expression of the nucleophosmin (NPM) nuclear-cytoplasmic shuttling protein. We found that NPM expression in Nf1(-/-) astrocytes was blocked by rapamycin in vitro and in vivo and that expression of a dominant-negative NPM mutant protein in Nf1(-/-) astrocytes rescued actin stress fiber formation and restored cell motility and proliferation to wild-type levels. Together, these data show that neurofibromin regulates actin cytoskeleton dynamics and cell proliferation through a mTOR/Rac1-dependent signaling pathway and identify NPM as a critical mTOR effector mediating these biological properties in Nf1-deficient astrocytes.

TSC1 sets the rate of ribosome export and protein synthesis through nucleophosmin translation.

Nucleophosmin (B23) is a nucleolar phosphoprotein that has been implicated in numerous cellular processes. In particular, nucleophosmin interacts with nucleolar components of newly synthesized ribosomes to promote ribosome nuclear export. Nucleophosmin is a classic mitogen-induced protein, with changes in its expression correlating with growth factor stimulation. In this study, we examined the underlying mechanism of nucleophosmin induction and showed that hyperproliferative signals emanating from oncogenic H-Ras(V12) cause tremendous increases in nucleophosmin protein expression. Nucleophosmin protein accumulation was dependent on mammalian target of rapamycin (mTOR) activation, as rapamycin completely prevented nucleophosmin induction. Consistent with this finding, genetic ablation of Tsc1, a major upstream inhibitor of mTOR, resulted in nucleophosmin protein induction through increased translation of existing nucleophosmin mRNAs. Increases in nucleophosmin protein accumulation were suppressed by reintroduction of TSC1. Induction of nucleophosmin through Tsc1 loss resulted in a greater pool of actively translating ribosomes in the cytoplasm, higher overall rates of protein synthesis, and increased cell proliferation, all of which were dependent on efficient nucleophosmin nuclear export. Nucleophosmin protein accumulation in the absence of Tsc1 promoted the nuclear export of maturing ribosome subunits, providing a mechanistic link between TSC1/mTOR signaling, nucleophosmin-mediated nuclear export of ribosome subunits, protein synthesis levels, and cell growth.