Real-World Patterns of Utilization and Costs Associated with Second-Generation Oral Antipsychotic Medication for the Treatment of Bipolar Disorder: A Literature Review.

OBJECTIVE: Treatment with second-generation antipsychotics (SGAs) for bipolar disorder, including bipolar I disorder (BD-I), is common. This review evaluated real-world utilization patterns with oral SGAs in the United States (US) for bipolar disorder (and BD-I specifically when reported) and economic burden associated with these patterns. METHODS: Structured, systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database identified primary research studies (published 2008-2018) describing real-world SGA use in adults with bipolar disorder/BD-I. RESULTS: Among 769 studies screened, 39 met inclusion criteria. Most studies (72%) were analyses of commercial or Medicare/Medicaid claims databases. Patient-related (eg, demographic, comorbidities) and disease-related (eg, mania, psychosis) factors were associated with prescribed SGA. Suboptimal utilization patterns (ie, nonadherence, nonpersistence, treatment gaps, medication switching, and discontinuation) were common for patients treated with SGAs. Also common were SGAs prescribed with another psychotropic medication and SGA combination treatment (use of ≥2 SGAs concurrently). Suboptimal adherence and SGA combination treatment were both associated with increased health care resource use (HCRU); suboptimal adherence was associated with higher total direct medical and indirect costs. LIMITATIONS: Different definitions for populations and concepts limited between-study comparisons. Focusing on SGAs limits contextualizing findings within the broader treatment landscape (eg, lithium, anticonvulsants). Given the nature of claims data, prescribing rationale (eg, acute episodes vs maintenance) and factors influencing observed utilization patterns could not be fully derived. CONCLUSION: Despite increased use of SGAs to treat bipolar disorder over the last decade, reports of suboptimal utilization patterns of SGAs (eg, nonadherence, nonpersistence) were common as was combination treatment. Patterns of SGA use associated with additional HCRU and/or costs were suboptimal adherence and SGA combination treatment; economic consequences associated with other utilization patterns (eg, nonpersistence) were unclear. Strategies to improve SGA treatment continuity, particularly adherence, may improve clinical and economic outcomes among people living with bipolar disorder.

The Economic Burden of Bipolar Disorder in the United States: A Systematic Literature Review.

Bipolar disorder (BD) is a mood disorder with subtypes characterized by episodes of mania, hypomania, and/or depression. BD is associated with substantial economic burden, and the bipolar I disorder (BD-I) subtype is associated with high medical costs. This review further evaluated the economic burden of BD and BD-I in the United States (US), describing health-care resource utilization (HCRU) and sources of direct medical and indirect costs. Data were obtained from systematic searches of MEDLINE®, EMBASE®, and National Health Service Economic Evaluation Database. Citations were screened to identify primary research studies (published 2008-2018) on the economic burden of BD/BD-I or its treatment in real-world settings. Reported costs were converted to 2018 US dollars. Of identified abstracts (N=4111), 56 studies were included. The estimated total annual national economic burden of BD/BD-I was more than $195 billion, with approximately 25% attributed to direct medical costs. Individuals with BD/BD-I used health-care services more frequently and had higher direct medical costs than matched individuals without the disease. Drivers of higher direct costs included frequent psychiatric interventions, presence of comorbid medical/psychiatric conditions, and both suboptimal medication adherence and clinical management. Indirect costs (eg, unemployment, lost work productivity for patients/caregivers) accounted for 72-80% of the national economic burden of BD/BD-I. Different definitions for study populations and cost categories limited comparisons of economic outcomes. This review builds on existing literature describing the economic burden of BD and confirmed cost drivers of BD/BD-I. Improved clinical management of BD/BD-I and associated comorbidities, together with better medication adherence, may reduce health-care costs and improve patient outcomes.

Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

PURPOSE: Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. METHODS: A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. FINDINGS: Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. IMPLICATIONS: Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications.

Costs of providing infusion therapy for patients with inflammatory bowel disease in a hospital-based infusion center setting.

AIMS: Inflammatory bowel disease (IBD) (e.g. ulcerative colitis [UC] and Crohn's disease [CD]) severely impacts patient quality-of-life. Moderate-to-severe disease is often treated with biologics requiring infusion therapy, adding incremental costs beyond drug costs. This study evaluates US hospital-based infusion services costs for treatment of UC or CD patients receiving infliximab or vedolizumab therapy. MATERIALS AND METHODS: A model was developed, estimating annual costs of providing monitored infusions using an activity-based costing framework approach. Multiple sources (published literature, treatment product inserts) informed base-case model input estimates. RESULTS: The total modeled per patient infusion therapy costs in Year 1 with infliximab and vedolizumab was $38,782 and $41,320, respectively, and Year 2+, $49,897 and $36,197, respectively. Drug acquisition cost was the largest total costs driver (90-93%), followed by costs associated with hospital-based infusion provision: labor (53-56%, non-drug costs), allocated overhead (23%, non-drug costs), non-labor (23%, non-drug costs), and laboratory (7-10%, non-drug costs). LIMITATIONS: Limitations included reliance on published estimates, base-case cost estimates infusion drug, and supplies, not accounting for volume pricing, assumption of a small hospital infusion center, and that, given the model adopts the hospital perspective, costs to the patient were not included in infusion administration cost base-case estimates. CONCLUSIONS: This model is an early step towards a framework to fully analyze infusion therapies' associated costs. Given the lack of published data, it would be beneficial for hospital administrators to assess total costs and trade-offs with alternative means of providing biologic therapies. This analysis highlights the value to hospital administrators of assessing cost associated with infusion patient mix to make more informed resource allocation decisions. As the landscape for reimbursement changes, tools for evaluating the costs of infusion therapy may help hospital administrators make informed choices and weigh trade-offs associated with providing infusion services for IBD patients.

The economic implications of switching to rivaroxaban from enoxaparin plus vitamin K antagonist in the treatment of venous thromboembolism.

OBJECTIVE: Venous thromboembolism (VTE) impacts ∼900,000 individuals annually in the US, causing up to 100,000 deaths. Patients experiencing VTE have heightened risk of recurrence. Initial parenteral anti-coagulation is standard therapy for acute VTE followed by ≥3 months of warfarin, which introduces the risk of major bleeding. Balancing increased risks of bleeding and recurrent VTE remains challenging. Recent clinical trials suggest that rivaroxaban, an oral direct inhibitor of factor Xa, provides an effective, safe, simplified approach to treatment. This study considers the economic implications of these data. METHODS: This study modeled inpatient, acute, and 1-year VTE costs for a hypothetical commercial plan with 1 million members. At baseline, all VTE patients receive standard therapy. Alternatively, 25% are instead treated with rivaroxaban. Model inputs are trial- and literature-based. RESULTS: Standard therapy for VTE consumes 9474 inpatient days ($31.6 million). Added to that is treatment for 74 recurrences ($1.4 million); major and non-major bleed events ($1 million); and direct costs of anti-coagulation ($5.3 million). Alternatively, a 25% shift to oral anti-coagulation with rivaroxaban reduces inpatient days (by 5%); associated acute-care costs (by 2%); recurrences and costs (by 6%). Four major bleeding events are prevented, at the cost of one additional non-major bleeding event, which, taken together, reduce net utilization by 9%. Direct costs of anti-coagulation increase by 5%. CONCLUSION: The reduction in inpatient utilization, recurrences, and major bleeding resulting from a 25% shift from standard therapy to rivaroxaban following acute VTE would conserve ∼$860,475 for every 1 million commercial health plan enrollees.

The economic burden to medicare of stroke events in atrial fibrillation populations with and without thromboprophylaxis.

Some 3 million people in the United States have atrial fibrillation (AF). Without thromboprophylaxis, AF increases overall stroke risk 5-fold. Prevention is paramount as AF-related strokes tend to be severe. Thromboprophylaxis reduces the annual incidence of stroke in AF patients by 22%-62%. However, antithrombotics are prescribed for only about half of appropriate AF patients. The study team estimates the economic implications for Medicare of fewer stroke events resulting from increased thromboprophylaxis among moderate- to high-risk AF patients. The decision model used considers both reduced stroke and increased bleeding risk from thromboprophylaxis for a hypothetical cohort on no thromboprophylaxis (45%), antiplatelets (10%), and anticoagulation (45%). AF prevalence, stroke risk, and stroke risk reduction are adjusted for age, comorbidities, and anticoagulation/antiplatelet status. Health care costs are literature based. At baseline, an estimated 24,677 ischemic strokes, 9127 hemorrhagic strokes, and 9550 bleeding events generate approximately $2.63 billion in annual event-related health care costs to Medicare for every million AF patients eligible for thromboprophylaxis. A 10% increase in anticoagulant use in the untreated population would reduce stroke events by 9%, reduce stroke fatalities by 9%, increase bleed events by 5%, and reduce annual stroke/bleed-related costs to Medicare by about $187 million (7.1%) for every million eligible AF patients. A modest 10% increase in the use of thromboprophylaxis would reduce event-related costs to Medicare by 7.1%, suggesting a compelling economic motivation to improve rates of appropriate thromboprophylaxis. New oral anticoagulants offering better balance between the risks of stroke and major bleeding events may improve these clinical and economic outcomes.

Budget impact analysis of tapentadol extended release for the treatment of moderate to severe chronic noncancer pain.

BACKGROUND: Opioids are commonly used to manage chronic pain. Although traditional µ-opioids are effective in reducing pain, they are often associated with opioid-induced side effects (OISEs) that can limit treatment effectiveness. Studies have shown that tapentadol extended release (ER) has a lower incidence of gastrointestinal adverse events than oxycodone controlled release (CR) at equianalgesic doses. OBJECTIVE: A model was developed to estimate the budget impact of placing tapentadol ER on a hypothetical US health plan formulary of Schedule II long-acting opioids. METHODS: We estimated annual direct health care costs for patients who received 6-month therapy with long-acting formulations of tapentadol, oxycodone, morphine, hydromorphone, oxymorphone, or fentanyl. Costs included medications, copayments, OISE management, and switching/discontinuation. Published estimates of incidence/prevalence, OISEs, and pain management resources and costs were used. The base case analysis assumed a 10% formulary share of tapentadol ER with a 10% decrease of oxycodone CR. The resulting per-member per-month (PMPM) formulary cost differences and results of a 1-way sensitivity analysis are reported. RESULTS: In a health plan of 500,000 members, 2600 (0.52%) are estimated to experience chronic pain annually. Adding tapentadol ER to the formulary was associated with an annual budget savings of $148,945 ($0.0248 PMPM). This savings was achieved through a decrease in both pharmacy costs ($144,062; $0.0240 PMPM) and medical costs ($4883; $0.0008 PMPM). Cost decreases were driven by lower daily average consumption and fewer OISEs with tapentadol ER versus oxycodone CR, leading to reduced resource utilization over 6 months of treatment. Sensitivity analyses showed results were most sensitive to drug acquisition costs. CONCLUSIONS: Our results suggest that replacing 10% of oxycodone CR's formulary share with tapentadol ER would decrease the overall budget of a health plan with 500,000 members. Placing tapentadol ER on a health plan formulary may result in a reduction in both pharmacy and medical costs.

Clinical simulation model of long-acting opioids for treatment of chronic non-cancer pain in the United States.

OBJECTIVE: To evaluate costs and outcomes associated with initial tapentadol ER vs oxycodone CR for the treatment of chronic non-cancer pain (CNCP) in the US. METHODS: This study developed a Monte-Carlo simulation based on the scientific foundation established by published models of long-acting opioids (LAO) in patients having moderate-to-severe CNCP. It estimates costs and outcomes associated with the use of tapentadol ER vs oxycodone CR over a 1-year period from the perspective of a US payer. LAO effectiveness and treatment-emergent adverse event (TEAE) rates are derived from clinical trials of tapentadol ER vs oxycodone CR; other inputs are based on published literature supplemented sparingly with clinical opinion. Sensitivity analyses consider the impact of real-world dosing patterns for LAO on treatment costs. RESULTS: Initial tapentadol ER consistently demonstrates better outcomes than initial oxycodone CR (proportion of patients achieving adequate pain relief and no GI TEAE; acute TEAE-free days; days free of chronic constipation; quality-adjusted life days; productive working hours). While total costs with initial tapentadol ER are slightly (2.2%) higher than with initial oxycodone CR, nearly twice as many modeled patients in the initial tapentadol ER arm (29% vs 15%) achieve adequate pain relief and no GI TEAE compared to initial oxycodone CR. In sensitivity analyses, tapentadol ER becomes a dominant strategy when real-world dosing patterns are considered. CONCLUSION: The additional costs to produce better outcomes (pain relief and no GI TEAE) associated with tapentadol ER are small in the context of double the likelihood of a patient response with tapentadol ER. When daily average consumption (DACON) for oxycodone CR is factored into the analysis, initial tapentadol ER becomes a dominant strategy. Our findings are both strengthened, and limited by the use of randomized trial-centric input parameters. These results should be validated as inputs from clinical practice settings become available.