Association of antipsychotic treatment switching in patients with schizophrenia, bipolar, and major depressive disorders.

Aims: To evaluate the association of relapse and healthcare resource utilization in patients with schizophrenia (SZ), bipolar disorder (BD), or major depressive disorder (MDD) who switched antipsychotic medication versus those who did not.Materials and methods: Medicaid claims from six US states spanning six years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD, or MDD, and for the subset of patients who also had ≥1 extrapyramidal symptoms (EPS) diagnosis at baseline, times to the following outcomes were analyzed: underlying disease relapse, other psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission, and EPS diagnosis.Results: Switchers (N = 10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank p < .001) than non-switchers (N = 31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the two-year study period. Subgroup analysis of those with ≥1 EPS diagnosis revealed similar associations.Limitations: Only association, not causation, may be inferred, and there may be differences between the patient groups in parameters not evaluated.Conclusions: These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for patients who switched antipsychotics than for those who did not, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BD, and MDD. This may be attributed to more-severely ill patients being less responsive than those with less-severe illness, which, in turn, may require more episodes of switching.

Deutetrabenazine for tardive dyskinesia and chorea associated with Huntington's disease: a review of clinical trial data.

Introduction: Huntington's disease (HD)-associated chorea and tardive dyskinesia (TD) are hyperkinetic movement disorders that can have deleterious effects on patients' quality of life (QoL). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, was approved by the US Food and Drug Administration (FDA) for the treatment of HD-associated chorea and TD. It is structurally similar to tetrabenazine, an FDA-approved compound for treatment of chorea that is widely used off-label for treatment of TD, but has deuterium modifications that improve its pharmacokinetic profile.Areas covered: Herein, the authors cover the key clinical trials with deutetrabenazine in patients with HD-associated chorea (First-HD and ARC-HD) and in patients with TD (ARM-TD, AIM-TD, and RIM-TD).Expert opinion: Deutetrabenazine demonstrates consistent efficacy across patient types regardless of underlying psychiatric illness, or through use of dopamine-receptor antagonists (DRAs), which are the primary cause of TD. The safety profile of deutetrabenazine in clinical trials is similar to that of placebo. Long-term extension studies in both HD-associated chorea and TD show consistent efficacy and safety. Deutetrabenazine will likely be an integral part of the treatment strategy for HD-associated chorea and TD. Meanwhile, its potential to treat other hyperkinetic movement disorders is still under investigation.

An Ecological Function Approach to Managing Harmful Cyanobacteria in Three Oregon Lakes: Beyond Water Quality Advisories and Total Maximum Daily Loads (TMDLs).

The Oregon Department of Environmental Quality (ODEQ) uses Total Maximum Daily Load (TMDL) calculations, and the associated regulatory process, to manage harmful cyanobacterial blooms (CyanoHABs) attributable to non-point source (NPS) pollution. TMDLs are based on response (lagging) indicators (e.g., measurable quantities of NPS (nutrients: nitrogen {N} and phosphorus {P}), and/or sediment), and highlight the negative outcomes (symptoms) of impaired water quality. These response indicators belatedly address water quality issues, if the cause is impaired riparian functions. Riparian functions assist in decreasing the impacts of droughts and floods (through sequestration of nutrients and excess sediment), allow water to remain on the land surface, improve aquatic habitats, improve water quality, and provide a focus for monitoring and adaptive management. To manage water quality, the focus must be on the drivers (leading indicators) of the causative mechanisms, such as loss of ecological functions. Success in NPS pollution control, and maintaining healthy aquatic habitats, often depends on land management/land use approaches, which facilitate the natural recovery of stream and wetland riparian functions. Focusing on the drivers of ecosystem functions (e.g., vegetation, hydrology, soil, and landform), instead of individual mandated response indicators, using the proper functioning condition (PFC) approach, as a best management practice (BMP), in conjunction with other tools and management strategies, can lead to pro-active policies and approaches, which support positive change in an ecosystem or watershed, and in water quality improvement.

Efficacy, safety, and quality-of-life of treatments for acute relapses of multiple sclerosis: results from a literature review of randomized controlled trials.

BACKGROUND: Intravenous methylprednisolone (IVMP), repository corticotropin injection (RCI), plasmapheresis (PMP), and intravenous immunoglobulin (IVIG) are used in the treatment of acute multiple sclerosis (MS) relapse. A systematic literature review (SLR) of randomized controlled trials (RCTs) was conducted to examine the highest quality evidence available for these therapies. METHODS: English-language articles were searched in MEDLINE, Embase, and Cochrane Library through May 2016 per Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards. MS conferences, SLRs, and bibliographies of included studies were also searched. Eligible studies included adults treated with ≥1 aforementioned therapy. RESULTS: Twenty-three RCTs were identified: 22 on efficacy, 11 on safety, and 3 on QOL (ie 18 IVMP, 2 RCI, 2 PMP, and 2 IVIG). IVMP and RCI improved relapse-related disability; however, IVIG and PMP showed inconsistent efficacy. QOL data were only ascertained for IVMP. CONCLUSIONS: RCTs indicate IVMP and RCI are efficacious and well tolerated treatments for MS relapse. Overall, many RCTs were dated, with sample sizes of fewer than 30 patients and no definitions for relapse nor clinically significant change. Contemporary evidence generation for all relapse treatments of interest, across efficacy, safety, and QOL outcomes, is still needed.

Assessing Dungeness River Functionality and Effectiveness of Best Management Practices (BMPs) Using an Ecological Functional Approach.

Effective stream and wetland Best Management Practices (BMPs) restore the physical processes associated with ecological functions to their Proper Functioning Condition (PFC, i.e., the highest attainable ecological status of a riparian area without consideration of economic, administrative, or social constraints). Ecological functions connect stream monitoring and management to mitigate the causes of ecosystem degradation and enhance restoration. The ecological function approach supports sustainable management of many ecosystem services including water quality, water stability (aquifer recharge), and fish and wildlife habitats. The 1993 Forest Ecosystem Management Assessment Team (FEMAT) report listed the Dungeness River as a Tier 1 key watershed, noted that watersheds are the logical spatial unit for ecosystem management, and that watersheds are important in species management, and understanding the interdependence of physical processes. Watersheds are at the spatial scale where physical and biological disturbances can be observed, and where management constraints and planning options for restoration objectives and strategies can be readily assessed. The US Forest Service (USFS) developed a management strategy for the Middle Dungeness River, and in the 1990s, the Upper Dungeness River was listed as impaired due to sediment, which initiated a US Forest Service change to land management practices. The Lower Dungeness River and bay are listed as impaired due to fecal coliform contamination. Assessing and monitoring the drivers of ecosystem function (vegetation, hydrology, soil, and landform) as part of a watershed adaptive management plan, and implementing BMPs to increase ecological functions, will improve aquatic habitat and water quality. Most BMPs, such as Total Maximum Daily Loads (TMDLs), attempt to improve water quality by reducing the amount of external pollutants reaching the impacted waterbodies, but do not focus on improving the watershed functions. The Proper Functioning Condition (PFC) approach is used to examine the condition of wetlands and streams and provide guidance for quantitative approaches (e.g., TMDL, remote sensing) used in watershed restoration. Improving watershed functions is a BMP that facilitates increased flows of water, nutrients, sediment, and other materials, and improves habitat quality. Using improved watershed functions as a BMP, facilitated by the use of remote sensing, TMDLs, and the PFC methodology is a more effective means of reducing risks across a watershed than by using TMDLs alone.

A Retrospective Medical Record Review of Utilization Patterns and Medical Resource Use Associated with Repository Corticotropin Injection among Patients with Rheumatologic Diseases in the United States.

INTRODUCTION: Repository corticotropin injection (RCI) has anti-inflammatory and immune-modulatory effects and is approved for multiple indications, including several rheumatologic conditions. The aims of this nationally representative, retrospective, observational study were to describe patient characteristics, RCI treatment patterns, and barriers to RCI use in patients with rheumatologic disease, and to compare medical resource use (MRU) before and after RCI therapy. METHODS: A random sample of US physicians was recruited to abstract the medical records of deidentified patients with a diagnosis of rheumatoid arthritis (RA), psoriatic arthritis (PsA), dermatomyositis/polymyositis (DM/PM), or systemic lupus erythematosus (SLE) who had been treated with RCI in the previous 24 months. Patient characteristics and patterns of RCI use were identified. Mean MRU in the 3 months before and after RCI therapy was compared using paired-samples t tests. RESULTS: A total of 449 physicians abstracted the medical records of 217 RA, 190 PsA, 254 DM/PM, and 95 SLE patients. In all groups combined, patients had received a mean of 3.3 treatment medications before initiating RCI. Most patients (75%-94%) were receiving RCI for the first time, indicating that repeated courses of RCI were uncommon. RCI was used as bridge therapy in 18% of patients. Approximately 24% of patients encountered an obstacle in accessing RCI, primarily insurance-related. After RCI therapy, the number of hospitalizations and hospital days were significantly reduced for all cohorts (all P < 0.05), and the number of outpatient visits was significantly lower for all cohorts (P < 0.05) except the SLE cohort (P = 0.3230). Study limitations include potentially incomplete data in the medical records and a relatively short duration for capturing MRU changes. CONCLUSIONS: RCI was used primarily as late-line therapy in patients with rheumatologic diseases. Medical resource use was significantly lower in the 3 months after therapy compared with 3 months prior. This finding suggests that RCI may improve disease control and warrants further evaluation. FUNDING: Mallinckrodt Pharmaceuticals.

Demographics, treatment patterns, and healthcare utilization and cost of repository corticotropin injection in patients with systemic lupus erythematosus or rheumatoid arthritis.

OBJECTIVE: To evaluate healthcare resource utilization (HRU) and costs among patients who initiated repository corticotropin injection (RCI; H.P. Acthar Gel) treatment for rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). METHODS: Patients aged ≥18 years with ≥2 diagnoses for either RA or SLE between July 1, 2006 and April 30, 2015 were identified in the HealthCore Integrated Research Database. Index RCI date was the earliest date of a medical or pharmacy claim for RCI after diagnosis. Baseline characteristics, pre- and post-initiation HRU and costs were assessed using descriptive statistics. RESULTS: This study identified 180 RA patients (mean age = 60 years, 56% female) and 29 SLE patients (mean age = 45 years, 90% female) who initiated RCI. First RCI use averaged 7.1 and 22.6 months after the initial RA and SLE diagnosis, respectively. After RCI initiation, RA patients incurred significantly lower per-patient-per-month (PPPM) all-cause medical costs ($1,881 vs $682, p < .01) vs the pre-initiation period, driven by lower PPPM hospitalizations costs ($1,579 vs $503, p < .01). Overall PPPM healthcare costs were higher ($2,751 vs $5,487, p < .01) due to higher PPPM prescription costs ($869 vs $4,805, p < .01). Similarly, SLE patients had decreased PPPM hospitalization costs ($3,192 vs $799, p = .04) and increased PPPM prescription costs ($905 vs $7,443, p < .01) after initiating RCI; the difference in overall PPPM healthcare costs was not statistically significant likely, due to small sample size. CONCLUSION: This study, across a heterogeneous population of variable disease duration, described clinical and healthcare utilization and costs of RA and SLE patients initiating RCI in a real-world setting. We observed that patients receiving RCI had lower utilization and costs for medical services in both disease populations, which partially offset the increased prescription costs by 30% and 37%. Future research is needed to explore factors associated with RCI initiation and its impact on long-term outcomes.

Economic burden of sarcoidosis in a commercially-insured population in the United States.

BACKGROUND: Sarcoidosis is a multi-system inflammatory disorder characterized by the presence of non-caseating granulomas in involved organs. Patients with sarcoidosis have a reduced quality-of-life and are at an increased risk for several comorbidities. Little is known about the direct and indirect cost of sarcoidosis following the initial diagnosis. AIMS: To provide an estimate of the healthcare resource utilization (HCRU) and costs borne by commercial payers for sarcoidosis patients in the US. METHODS: Patients with a first diagnosis of sarcoidosis between January 1, 1998 and March 31, 2015 ("index date") were selected from a de-identified privately-insured administrative claims database. Sarcoidosis patients were required to have continuous health plan enrollment 12 months prior to and following their index dates. Propensity-score (1:1) matching of sarcoidosis patients with non-sarcoidosis controls was carried out based on a logistic regression of baseline characteristics. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched groups over the 12-month period following the index date ("outcome period"). RESULTS: A total of 7,119 sarcoidosis patients who met the selection criteria were matched with a control. Overall, commercial payers incurred $19,714 in mean total annual healthcare costs per sarcoidosis patient. The principle cost drivers were outpatient visits ($9,050 2015 USD, 46%) and inpatient admissions ($6,398, 32%). Relative to controls, sarcoidosis patients had $5,190 (36%) higher total healthcare costs ($19,714 vs $14,524; p < 0.001). Sarcoidosis patients also had significantly more work loss days (15.9 vs 11.3; p < 0.001) and work loss costs ($3,288 vs $2,527; p < 0.001) than matched controls. Sarcoidosis imposes an estimated total direct medical cost of $1.3-$8.7 billion to commercial payers, and an indirect cost of $0.2-$1.5 billion to commercial payers in work loss. CONCLUSIONS: Sarcoidosis imposes a significant economic burden to payers in the first year following diagnosis.

Clinical and Economic Evaluation of Repository Corticotropin Injection: A Narrative Literature Review of Treatment Efficacy and Healthcare Resource Utilization for Seven Key Indications.

INTRODUCTION: Repository corticotropin injection (RCI; H.P. Acthar® Gel; Mallinckrodt Pharmaceuticals Inc., Hampton, NJ) is a highly purified, prolonged-release porcine preparation of adrenocorticotropic hormone (ACTH) analogue that is FDA-approved for treatment of 19 autoimmune and inflammatory disorders. The diverse physiological actions of RCI at the melanocortin receptors (MCRs) affect processes involved in inflammation, pigmentation, steroidogenesis, and immunomodulation. Although RCI has been approved to treat inflammatory and autoimmune diseases for more than 60 years, recent progress in understanding both MCRs and the effects of RCI in modulating immune responses has led to increased interest in RCI as a therapeutic choice. The objective of this narrative literature review is to summarize key clinical and economic data on RCI treatment of seven disorders: infantile spasms (IS), multiple sclerosis (MS) relapses, proteinuria in nephrotic syndrome, rheumatoid arthritis (RA), dermatomyositis/polymyositis (DM/PM), systemic lupus erythematosus (SLE), and symptomatic sarcoidosis based on published literature and product information. An extended report is available as the Academy of Managed Care Pharmacy (AMCP) Formulary dossier for H.P. Acthar® Gel. METHODS: Key studies of clinical efficacy and healthcare utilization and cost from 1956 to 2016 are summarized. RESULTS: The evidence supports the efficacy of RCI across the seven indications. RCI is effective as a first-line therapy for IS. For the other six conditions, RCI may improve clinical outcomes during exacerbations or when the condition is resistant to conventional treatments. Use of RCI is associated with reduced use of biologics, corticosteroids, and disease-modifying antirheumatic drugs. Initiation of RCI therapy in patients with IS, MS, RA, SLE, or DM/PM has been associated with lower post-therapy healthcare utilization and medical costs, including decreases in hospitalizations, hospital length of stay, outpatient visits, and emergency department visits. CONCLUSION: The evidence suggests that RCI may improve inflammatory and autoimmune disease control and patient quality of life, particularly in complex patients, and yield healthcare cost savings that demonstrate the medicine's value. FUNDING: Mallinckrodt Pharmaceuticals Inc.

Medical resource utilization in dermatomyositis/polymyositis patients treated with repository corticotropin injection, intravenous immunoglobulin, and/or rituximab.

BACKGROUND: Dermatomyositis and polymyositis (DM/PM) are rare, incurable inflammatory diseases that cause progressive muscle weakness and can be associated with increased medical resource use (MRU). When corticosteroid treatment is unsuccessful, patients may receive intravenous immunoglobulin (IVIg), rituximab, or repository corticotropin injection (RCI). This study compared real-world, non-medication MRU between patients treated with RCI and those treated with IVIg and/or rituximab for DM/PM. METHODS: Claims of DM/PM patients were analyzed from the combination of three commercial health insurance databases in the United States from July 2009 to June 2014. Patients treated with RCI were propensity score matched to those treated with IVIg, rituximab, and both (IVIg+rituximab) based on demographics, prior clinical characteristics, and prior MRU. Per-patient per-month (PPPM) MRU and costs were compared using Poisson regression and generalized linear modeling, respectively. RESULTS: One-hundred thirty-two RCI, 1,150 IVIg, and 562 rituximab patients had an average age of 52.6, 46.6, and 51.7 years, respectively, and roughly two-thirds were female. After matching, there were no significant differences in demographics or prior clinical characteristics. RCI patients had fewer PPPM hospitalizations (0.09 vs 0.17; P=0.049), shorter length of stay (LOS; 3.24 days vs 4.55 days; P=0.004), PPPM hospital outpatient department (HOPD) visits (0.60 vs 1.39; P<0.001), and PPPM physician office visits (2.01 vs 2.33; P=0.035) than IVIg. RCI had fewer PPPM HOPD visits (0.56 vs 0.92; P<0.001) than rituximab. Patients treated with RCI had shorter LOS (2.18 days vs 5.15; P<0.001) and less PPPM HOPD visits (0.53 vs 1.26; P<0.001) than IVIg+rituximab. Total non-medication PPPM costs were 23%-75% lower for RCI compared to IVIg ($2,126 vs $3,964; P<0.001), rituximab ($2,008 vs $2,607; P=0.018), and IVIg+rituximab ($1,234 vs $4,858; P<0.001). CONCLUSION: Patients treated with RCI had less PPPM non-medication MRU and costs than those treated with IVIg and/or rituximab, particularly in the hospital setting where significant costs are incurred.

Healthcare Costs and Resource Utilization in Patients with Infantile Spasms Treated with H.P. Acthar Gel(®).

INTRODUCTION: The purpose of this study was to describe healthcare resource utilization and costs resulting from early (within 30 days of diagnosis) versus late (>30 days after diagnosis) treatment with prescriptions for H.P. Acthar(®) Gel (repository corticotropin injection; Acthar; Mallinckrodt) to manage infantile spasms (IS). METHODS: We included all patients in the Truven Health MarketScan(®) Commercial Claims and Encounters Database and the Truven Health MarketScan Multi-State Medicaid Database who were diagnosed with IS from 2007 to 2012. We performed unadjusted and adjusted regressions examining the relationship between healthcare resource utilization variables and their associated costs to compare outcomes in the early and late Acthar users. RESULTS: A total of 252 patients with IS who received Acthar fit our study criteria; 191 (76%) were early Acthar users. In adjusted analyses, we found that early Acthar use was associated with, on average, 3.8 fewer outpatient services (99% CI 0.7-6.7 fewer services). We did not find significant associations between early prescriptions for Acthar and number of hospitalizations, emergency room visits, prescription medications filled, or total costs of health services. CONCLUSION: Patients prescribed Acthar within 30 days of their IS diagnoses tended to have fewer outpatient services performed compared to patients prescribed Acthar later in the disease process. Although additional research is needed to confirm these exploratory findings, physicians may consider early treatment with Acthar to manage IS. FUNDING: This study was funded by a grant to the University of Washington from Mallinckrodt Pharmaceuticals.

Healthcare resource utilization and work loss in dermatomyositis and polymyositis patients in a privately-insured US population.

Background Dermatomyositis and polymyositis (DM/PM) are inflammatory myopathies characterized by muscle inflammation/weakness. Patients with DM/PM have a reduced quality-of-life and are at an increased risk for several comorbidities. Studies have assessed the incidence and prevalence of DM/PM; however, no study has estimated the burden of the diseases in terms of both healthcare resource utilization (HCRU) and work loss incurred by patients. Objective To provide a comprehensive, current estimate of the annual HCRU and work loss in DM/PM patients in the US. Methods All patients (aged 18-64 years) with a first diagnosis of DM/PM between January 1, 1998 and March 31, 2014 ('index date') were selected from a de-identified privately-insured administrative claims database. DM/PM patients were required to have continuous health-plan enrollment 12 months prior to and following their index date. Propensity-score (1:1) matching of DM/PM patients with non-DM/PM controls was carried out based on a logistic regression of demographic characteristics, comorbidities, costs, and HCRU to control for these confounding factors. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched DM/PM and the non-DM/PM cohorts over the 12-month period after the index date ('outcome period'). Results Of the 2617 DM/PM patients that met sample selection criteria, 2587 (98.9%) were matched with a non-DM/PM control. During the outcome period, DM/PM patients had significantly increased HCRU across places of service, including 44% more inpatient admissions (3.6 vs 2.5, p < 0.001), increased visits with specialists such as rheumatologists, neurologists and physical therapists, and filled 4.7 more prescriptions (32.2 vs 27.5, p < 0.001) than matched control patients. The increased HCRU led to significantly more medically-related work loss among DM/PM patients than matched controls (p < 0.001). Conclusions DM/PM imposes a substantial increase in healthcare resource use and is associated with statistically significantly greater work loss in the first year following diagnosis.

An ecological function and services approach to total maximum daily load (TMDL) prioritization.

Prioritizing total maximum daily load (TMDL) development starts by considering the scope and severity of water pollution and risks to public health and aquatic life. Methodology using quantitative assessments of in-stream water quality is appropriate and effective for point source (PS) dominated discharge, but less so in watersheds with mostly nonpoint source (NPS) related impairments. For NPSs, prioritization in TMDL development and implementation of associated best management practices should focus on restoration of ecosystem physical functions, including how restoration effectiveness depends on design, maintenance and placement within the watershed. To refine the approach to TMDL development, regulators and stakeholders must first ask if the watershed, or ecosystem, is at risk of losing riparian or other ecologically based physical attributes and processes. If so, the next step is an assessment of the spatial arrangement of functionality with a focus on the at-risk areas that could be lost, or could, with some help, regain functions. Evaluating stream and wetland riparian function has advantages over the traditional means of water quality and biological assessments for NPS TMDL development. Understanding how an ecosystem functions enables stakeholders and regulators to determine the severity of problem(s), identify source(s) of impairment, and predict and avoid a decline in water quality. The Upper Reese River, Nevada, provides an example of water quality impairment caused by NPS pollution. In this river basin, stream and wetland riparian proper functioning condition (PFC) protocol, water quality data, and remote sensing imagery were used to identify sediment sources, transport, distribution, and its impact on water quality and aquatic resources. This study found that assessments of ecological function could be used to generate leading (early) indicators of water quality degradation for targeting pollution control measures, while traditional in-stream water quality monitoring lagged in response to the deterioration in ecological functions.