Risk Factors Associated with Falls and Fractures Following Prescription of Opioids Among Privately Insured Patients with Osteoarthritis.

Background: While prior research has shown that patients with osteoarthritis (OA) who are prescribed opioids have higher rates of falls and fractures following drug initiation, there is a limited body of work establishing a comprehensive model of factors that influence the risk of falls or fractures among these patients. Objective: Opioids are associated with negative clinical outcomes, including increased risk of falls and fractures. This study assessed the frequency, treatment characteristics, and risk factors associated with falls or fractures among patients with OA taking opioids. Methods: Optum Healthcare Solutions, Inc data (January 2012-March 2017) were used to identify patients over 18 with at least 2 diagnoses of hip and/or knee OA, and at least 90 days' supply of opioids. Patients with cancer were excluded. Falls or fractures outcomes were assessed in the 36-month follow-up period after the date of the first opioid prescription after first OA diagnosis. Demographic, treatment, and clinical characteristics associated with falls or fractures were assessed using logistic regression. Results: Of 16 663 patients meeting inclusion criteria, 3886 (23%) had at least 1 fall or fracture during follow-up. Of these 3886 patients, 1349 (35%) had at least 1 fall with an average of 3 fall claims, and 3299 (85%) patients had at least 1 fracture with an average of 8 claims during follow-up. Spine (15.8%) and hip (12.5%) fractures were most common. Median time to fall or fracture was 18.6 and 13.9 months, respectively. Significant (P<.05) risk factors associated with at least 1 fall or fracture during the follow-up period included alcohol use (odds ratio [OR], 3.41), history of falling (OR, 2.19), non-tramadol opioid use (OR, 1.31), age (OR, 1.03), benzodiazepine use (OR, 1.21), and at least 1 osteoporosis diagnosis (OR, 2.06). Discussion: This study is among only a few that clearly identifies the substantial impact and frequency of falls and fractures associated with prescribing non-tramadol opioids to patients with OA. Findings suggest that fall or fracture risks need to be considered when managing OA pain with opioids. Conclusion: Falls and fractures impose a major clinical burden on patients prescribed opioids for OA-related pain management. Falls or fracture risks should be an important consideration in the ongoing treatment of patients with OA.

All-Cause Health Care and Work Loss Burden Associated With Nonsteroidal Anti-Inflammatory Drug and Opioid Treatment in Employed Patients With Osteoarthritis.

INTRODUCTION: This study estimated all-cause health care resource utilization (HRU) and costs and work loss outcomes associated with pain management of employed patients with osteoarthritis of the hip and/or knee. METHODS: Optum Health Care Solutions data were analyzed for employed patients prescribed nonsteroidal anti-inflammatory drugs, tramadol, or nontramadol opioids following diagnoses of osteoarthritis of the hip and/or knee. A pre-post design was used to evaluate changes in all-cause HRU and costs, and work loss days and associated costs. RESULTS: Costs rose for patients in all three cohorts (up to 198.3% for health care costs [tramadol] and up to 178.7% for work loss costs [tramadol]). Greatest increases in all-cause HRU included inpatient visits (237.9% [nonsteroidal anti-inflammatory drugs]; 600% [tramadol]). CONCLUSIONS: Study results provide evidence of increases in all-cause HRU and costs and work loss days and associated costs.

Clinical and economic burden of prescribing tramadol and other opioids for patients with osteoarthritis in a commercially insured population in the United States.

ABSTRACT: In 2019, the American College of Rheumatology conditionally recommended tramadol and conditionally recommended against nontramadol opioids for patients with hip and knee osteoarthritis. Although tramadol is known to be less prone to opioid use disorders, little is known about the differing magnitude of negative clinical outcomes, health care resource utilization, and costs of tramadol relative to nontramadol opioids. Administrative claims records for commercially insured patients with osteoarthritis who were prescribed opioids were used to compare clinical and cost outcomes during a 3-year follow-up period by conducting a pre-post analysis and a matched case-cohort analysis. Data for 14,491 patients were analyzed: 4048 (28%) were initiated on tramadol, and 10,443 (72%) were initiated on nontramadol opioids. After matching, 4048 patients per cohort were analyzed. In each empirical analysis, tramadol patients did develop opioid use disorders; however, opioid use disorder rates were 3.5-fold higher in the nontramadol cohort (1.2% vs 4.2%). In addition, rates of other opioid-related clinical outcomes (falls, fractures, nausea, fatigue, and constipation) were also directionally lower among the tramadol cohort, although quantitatively similar (<5% difference) to the nontramadol cohort. Finally, in both analyses, the nontramadol cohort incurred higher levels of inpatient and emergency department visits and all-cause costs during the 3-year follow-up period. However, tramadol patients incur a higher incremental change (+$24,013) in costs relative to their pretreatment baseline compared with nontramadol (+$18,191). These real-world findings demonstrated lower risks with tramadol relative to other opioids, albeit risks and increased health care costs were present with tramadol, highlighting the need for further strategies to improve outcomes.

A harm reduction model to assess the impact of new treatments for pain over standard of care among patients with osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects millions of adults in the United States and can result in substantial pain, functional impairment, and significant clinical and economic burden. To manage chronic pain associated with OA, treatment guidelines recommend a variety of pharmacologic treatments, including traditional oral nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 inhibitors (COX-2s), and opioids. While these drug treatments can be effective at pain management, they are also associated with significant clinical and economic burden. New treatments for chronic pain among patients with OA of the hip and/or knee have the potential to reduce the occurrence of such negative clinical outcomes, including cardiovascular events, renal events, and opioid use disorder (OUD), thereby reducing health care resource use (HRU) and medical costs. OBJECTIVE: To develop a harm reduction model (HRM) to assess potential reductions of negative clinical outcomes, HRU, and medical costs associated with the use of new treatments in place of oral NSAIDs, tramadol, and non-tramadol opioids among patients with OA of the hip and/or knee in the United States. METHODS: The HRM model integrated findings from the literature and inputs from a variety of sources, along with assumptions regarding potential ability of new treatments to replace existing treatments and market penetration into a unified framework to estimate outcomes and costs. The model outputs included estimated per-patient and population-level reductions in negative clinical outcomes associated with prescribing new treatments in place of oral NSAIDs or opioids along with number needed to treat (NNT) associated with new treatments. The model assumed that new treatments will primarily be used in place of non-tramadol opioids, but more modest adoption in place of oral NSAIDs and tramadol. RESULTS: Among patients with OA of the hip and/or knee who were prescribed oral NSAIDs, tramadol, or non-tramadol opioids for chronic use (≥ 90 days), the HRM estimated total cost savings of $3.8 billion, $5.1 billion, and $29.9 billion, respectively, from prescribing new treatments for OA pain over a 36-month period. The reduced economic burden was driven by significant reductions in the incidence of negative clinical outcomes. Estimates of the NNT to avoid a negative clinical event related to NSAID and opioid treatment initiation were low for most outcomes. Estimates of NNT associated with NSAID use ranged from 4 to 17 patients, depending on outcome, and estimates of NNT associated with opioid use was 35 non-tramadol and 134 tramadol patients for OUD and ranged from 6 to 21 patients for the other clinical outcomes, depending on treatment and outcome. CONCLUSIONS: Results from the HRM suggest that prescribing new treatments in place of oral NSAIDs and/or opioids for OA pain results in a potentially substantial reduction in patients experiencing negative clinical outcomes and reductions in all-cause HRU and costs. DISCLOSURES: This study was sponsored by Pfizer and Eli Lilly and Company. Silverman was a paid consultant to Pfizer and Eli Lilly and Company in connection with this study. Beck and Schepman are employees of Pfizer with stock and/or stock options. Robinson is an employee and minor stockholder of Eli Lilly and Company. Rice, White, and Fernan are employees of the Analysis Group, who were paid consultants to Pfizer and Eli Lilly and Company for this study and development of the manuscript.

Direct Costs of Opioid Abuse in an Insured Population in the United States.

OBJECTIVE: To (a) describe the demographics of opioid abusers; (b) compare the prevalence rates of selected comorbidities and the medical and drug utilization patterns of opioid abusers with patients from a control group, for the period from 1998 to 2002; and (c) calculate the mean annual per-patient total health care costs (e.g., inpatient, outpatient, emergency room, drug, other) from the perspective of a private payer. METHODS: An administrative database of medical and pharmacy claims from 1998 to 2002 of 16 self-insured employer health plans with approximately 2 million lives was used to identify "opioid abusers"-patients with claims associated with ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes for opioid abuse (304.0, 304.7, 305.5, and 965.0 [excluding 965.01]). A control group of nonabusers was selected using a matched sample (by age, gender, employment status, and census region) in a 3:1 ratio. Per-patient annual health care costs (mean total medical and drug costs) were measured in 2003 U.S. dollars. Multivariate regression techniques were also used to control for comorbidities and to compare costs with a benchmark of depressed patients. RESULTS: 740 patients were identified as opioid abusers, a prevalence of 8 in 10,000 persons aged 12 to 64 years continuously enrolled in health care plans for whom 12 months of data were available for calculating costs. Opioid abusers, compared with nonabusers, had significantly higher prevalence rates for a number of specific comorbidities, including nonopioid poisoning, hepatitis (A, B, or C), psychiatric illnesses, and pancreatitis, which were approximately 78, 36, 9, and 21 (P<0.01) times higher, respectively, compared with nonabusers. Opioid abusers also had higher levels of medical and prescription drug utilization. Almost 60% of opioid abusers had prescription drug claims for opioids compared with approximately 20% for nonabusers. Prevalence rates for hospital inpatient visits for opioid abusers were more than 12 times higher compared with nonabusers (P<0.01). Mean annual direct health care costs for opioid abusers were more than 8 times higher than for nonabusers ($15,884 versus $1,830, respectively, P < 0.01). Hospital inpatient and physician-outpatient costs accounted for 46% ($7,239) and 31% ($5,000) of opioid abusers' health care costs, compared with 17% ($310) and 50% ($906), respectively, for nonabusers. Mean drug costs for opioid abusers were more than 5 times higher than costs for nonabusers ($2,034 vs. $386, respectively, P<0.01), driven by higher drug utilization (including opioids) for opioid abusers. Even when controlling for comorbidities using a multivariate regression model of a matched control of depressed patients, the average health care costs of opioid abusers were 1.8 times higher than the average health care costs of depressed patients. CONCLUSION: The high costs of opioid abuse were driven primarily by high prevalence rates of costly comorbidites and high utilization rates of medical services and prescription drugs. DISCLOSURES: Funding for this research was provided by an unrestricted grant from Janssen Medical Affairs, L.L.C. and was obtained by authors Susan Vallow and Jeff Schein, who are employed by Janssen Medical Affairs, L.L.C. Nathaniel Katz is a consultant to Janssen and numerous other pharmaceutical companies that manufacture branded opioid products and nonopioid analgesics; authors Alan G. White, Howard G. Birnbaum, Milena N. Mareva, and Maham Daher disclose no potential bias or conflict of interest relating to this article. White served as principal author of the study. Study concept and design were contributed primarily by White, Vallow, Schein, and Katz. Analysis and interpretation of data were contributed by all authors. Drafting of the manuscript was primarily the work of White, and its critical revision was the work of White and Vallow. Statistical expertise was contributed by White, Birnbaum, and Daher, and administrative, technical, and/or material support was provided by Analysis Group, Inc., Boston, MA.

Assessment of Work Loss Associated With Prescription-Related Opioid Use Disorder: A Retrospective Analysis of Claims Data.

OBJECTIVE: Quantify work loss and costs associated with prescription opioid use disorder (OUD) from the employer perspective. METHODS: Retrospective claims analysis to compare missed work days and associated costs between employees with and without an OUD diagnosis in a 12-month period. RESULTS: Two thousand three hundred eleven matched-pairs of employees were compared. The mean (SD) number of days missed while waiting for disability benefits (0.24 [1.4] vs 0.17 [1.0]; P = 0.035), absenteeism due to disability claims (9.5 [40.9] vs 5.6 [30.0]; P < 0.001), and medical visits (17.8 [18.5] vs 10.0 [12.4]; P < 0.001) was higher for employees with OUD compared with those without, resulting in higher mean (SD) indirect cost estimates of $8193 ($14,694) per employee (OUD) versus $5438 ($13,683) per employee (no OUD) (P < 0.001). CONCLUSIONS: Prescription OUD is associated with significant work loss and may pose considerable economic burden on employers.

Economic Burden of Non-Infectious Inflammatory Eye Disease (NIIED) in a Commercially-Insured Population in the United States.

Purpose: To assess the economic burden of non-infectious inflammatory eyedisease (NIIED) in a commercially-insured population in the United StatesMethods: Adult patients with a NIIED diagnosis between 2006 and 2015 were selected from a de-identified, privately insured claims database and were matched 1:1 to a non-NIIED control. Ophthalmologic complications, direct healthcare resource use and costs, and indirect work loss (from the payer perspective) were calculated for a 12-month period and compared across the 2 cohorts.Results: Among the 14 876 matched pairs, NIIED patients were significantly more likely than controls to experience ocular complications, including glaucoma and cataracts (p < 0.001). NIIED patients had significantly higher healthcare resource utilization and costs compared with matched controls (relative difference 40%, p < 0.001). NIIED patients missed 12.2 days of work ($2925 annual work-loss costs), 46% more than non-NIIED patients (p < 0.001).Conclusion: NIIED imposes a significant clinical and economic burden, suggesting an unmet need for expanded access to alternative treatment options.

Predictors of High-cost Patients With Noninfectious Inflammatory Eye Diseases.

PURPOSE: Noninfectious inflammatory eye diseases (NIIEDs), such as uveitis, is a general term used to describe a complex mix of acute, chronic, allergic, and inflammatory disorders. Prior literature has established that, in addition to severe clinical burden, NIIEDs is associated with significant economic burden for US payers; however, no literature provides a current estimate of the economic burden associated with patients with high-cost NIIEDs. This study aimed to better understand the cost and resource use distribution and predictors of patients with high-cost NIIEDs. METHODS: This retrospective cohort study selected adult patients with NIIEDs from a large US administrative claims database between 2006 and 2015. Among the included patients, total all-cause health care costs were calculated for a randomly selected 12-month period. Patients in the top 20% of total all-cause health care costs were identified as high-cost patients; the remaining patients were identified as lower-cost patients. Patient demographic characteristics, clinical characteristics, cost, and health care resource utilization (HRU) were compared. Logistic regression models were used to determine characteristics associated with high-cost patients. FINDINGS: Patients with NIIEDs (n = 14,879) were categorized into 2976 high-cost and 11,903 lower-cost patients. High-cost patients with NIIEDs were significantly more likely to experience blindness, cataract, cystoid macular degeneration, retinal detachment, and visual disturbances during the follow-up period than the lower-cost patients (all P < 0.05). The high-cost patients accounted for ~77% of the total all-cause health care spend. High-cost patients incurred an average annual total health care cost of $59,873, and the top 1 percentile incurred $349,967 during the follow-up period. Hospitalization was a key cost driver among the high-cost patients, accounting for 50% of the total cost among the top 1 percentile of patients. High-cost patients were more likely to have specific autoimmune diseases, inpatient admission, and use of biologic and immunosuppressant agents. IMPLICATIONS: A small segment of patients with NIIEDs consumed most resources. This study identified several predictors based on patient characteristics and HRU that may help inform the profile of patients with NIIEDs with the highest health care needs. As such, patients with a given profile can be selected for targeted interventions by clinicians to potentially help improve quality of care and to reduce costs.

Modeling the potential impact of abuse-deterrent opioids on medical resource utilization.

Objectives: To extend a previously published manuscript on a model for estimating potential avoided medical events and cost savings in the US associated with the introduction of extended-release abuse-deterrent opioids and incorporate new methods of evaluating abuse deterrence using human abuse potential studies. Methods: A model was developed to estimate reductions in abuse-related events and annual savings in the US. Model inputs included: opioid abuse prevalence, abuse-deterrent opioid cost and effectiveness at deterring abuse, and opioid abuse-related events and costs. Direct (medical and drug) and indirect (work loss) cost savings (2017 US$) and abuse-related events were estimated assuming the replacement of the entire extended-release opioid market (brand and generic) by brand abuse-deterrent opioids. Results: Replacing the extended-release opioid market with abuse-deterrent opioids is estimated to lower annual abuse-related medical events by ∼13-31% (e.g. 78,000-186,000 emergency department visits) and lower annual medical costs by ∼$640 M-$1,538 M, depending on the abuse-deterrent technology (physical/chemical barrier or agonist/antagonist). Replacement of extended-release oxycodone with extended-release abuse-deterrent oxycodone is associated with the largest amount of cost savings and highest number of avoided medical events, followed by replacing extended-release morphine with an extended-release abuse-deterrent opioid. Replacement of transdermal fentanyl is associated with the smallest amount of cost savings and lowest number of avoided medical events. Conclusion: Agonist/antagonist abuse-deterrent opioid technology is associated with higher annual medical cost savings and more avoided events than physical/chemical barrier technology. Total net savings are dependent upon the abuse-deterrent opioid price relative to non-abuse-deterrent opioids.

The burden of non-infectious intraocular inflammatory eye diseases: a systematic literature review.

OBJECTIVE: Non-infectious inflammatory eye diseases (IEDs), although rare, are complex and varied and may result in detrimental effects. A systematic literature review was conducted on the clinical outcome and economic burden of IED. METHODS: The Ovid search platform (Wolters Kluwer) was used to access scientific literature databases, including MEDLINE, Embase, Cochrane libraries, Health Technology Assessment and the NHS Economic Evaluation database. The search strategy targeted clinical and economic outcomes research in 2009-2016. Titles and abstracts resulting from inclusion criteria were screened, and two reviewers independently extracted relevant information from the selected full-text articles. RESULTS: Thirty-nine papers met the inclusion criteria - 21 clinical trials, 7 database analyses, 6 non-systematic literature reviews with expert commentary, 3 chart reviews, and 2 surveys - which assessed steroids, immunosuppressants, implants and biologics. Patients experienced considerable morbidity, much of which was associated with corticosteroid use. The average annual healthcare costs of patients with IED were $13,728 to $32,268 in 2009 US dollars, which amounted to 3.1 to 8.3 times that of patients without IED. Steroid-releasing intraocular implants were associated with higher up-front costs, close monitoring requirements, potential for implant removal and increased rates of adverse ocular events than systemic steroids. CONCLUSIONS: IEDs are rare and complex conditions that threaten eyesight and impose considerable morbidity as well as a substantial economic burden. This review confirms that further research is needed to more fully explore the burden of IED and treatment-related adverse events, as well as appropriate means for clinicians to intensify treatment.

Quantitative characterization of the relationship between levels of extended corticosteroid use and related adverse events in a US population.

OBJECTIVE: This retrospective study assessed the incidence and timing of adverse events (AEs) among patients prescribed varying dose levels of corticosteroids in the US. METHODS: Patients with selected autoimmune or inflammatory disease diagnoses between 2006 and 2015 were identified from a privately insured administrative database. Patients were stratified into treatment cohorts based on dosage and length of corticosteroid use: intermittent use with duration <60 days, and three extended use cohorts with duration ≥60 days at low (≤7.5 mg/day), medium (>7.5-≤15 mg/day) or high (>15 mg/day) prednisone-equivalent dosage. The incidence of and time to corticosteroid-related AEs were assessed by cohort. RESULTS: A total of 78,704 patients met the selection criteria, of whom 9.5%, 11.0% and 8.6% were classified into the high-, medium-, and low-dose extended corticosteroid use cohorts, respectively. Corticosteroid exposure varied across study conditions, from 34% of dermatomyositis/polymyositis to 6% of psoriatic arthritis patients prescribed extended high dose. Hypertension, pneumonia and osteoporosis were the AEs with the highest incidence rates (41.9, 27.4 and 19.8 cases respectively per 1000 patient-months for the high-dose cohort). For most AEs, all levels of extended corticosteroid use exhibited significant risks of increased incidence compared to intermittent use. Some AEs had dose relationships, with higher dose correlated with higher incidence; other AEs had duration relationships with longer duration correlated with higher incidence regardless of dose. Average time to AE onset was relatively short, occurring at 2.3-6.7 months after corticosteroid initiation. CONCLUSIONS: Through a rigorous quantitative characterization, extended steroid exposure was associated with increased incidence and earlier onset of AEs among privately insured adults in the US.

Healthcare resource use and cost associated with varying dosages of extended corticosteroid exposure in a US population.

AIMS: To quantify healthcare resource use (HCRU) and costs associated with varying levels of corticosteroid exposure. MATERIALS AND METHODS: Patients with a diagnosis of selected autoimmune and inflammatory diseases between 1 January 2006 and 30 September 2015 ("study period") were selected from a de-identified, privately-insured claims database. Patients were stratified into four treatment cohorts based on the dosing and duration of continuous corticosteroid use following disease diagnosis: intermittent use with <60 days of corticosteroid use and ≥60 days of corticosteroid use with low (≤7.5 mg/day), medium (>7.5-≤15 mg/day), or high (>15 mg/day) dosage. Patients were followed from the date of their highest dose episode of corticosteroid use ("treatment index date") until the earliest of the end of continuous corticosteroid use +30 days, disenrollment from health plan, or the end of the study period ("follow-up period"). HCRU and costs in the follow-up period were compared across treatment cohorts. RESULTS: Of 78,704 patients who were identified for study inclusion, 29% had extended corticosteroid use lasting ≥60 days, and 71% had intermittent use. On average, patients in the high-dose cohort incurred twice the cost of intermittent users ($68,408 vs $32,690 in annualized total all-cause healthcare costs, USD). Adverse event-related medical costs accounted for ∼40% of medical costs, and were higher than disease-related medical costs for all cohorts with extended corticosteroid exposure. Comparing the high-dose and low-dose cohorts, the smaller savings in disease-related prescriptions ($1,680) occurred along with a much larger cost in adverse event-related spend ($13,464). LIMITATIONS: The impact of corticosteroids may be under-estimated because of conservative follow-up duration, and administrative data may contain inaccuracies in coding. CONCLUSIONS: Steroid use, especially at higher doses, is associated with higher HCRU and costs.

Projecting the cost, utilization, and patient care impact of prescribing extended release non-abuse-deterrent opioids to chronic pain patients.

OBJECTIVES: To estimate healthcare resource utilization, associated costs, and number needed to harm (NNH) from a physician's decision to prescribe extended-release (ER) non-abuse-deterrent opioids (non-ADO) as compared to ER ADOs in a chronic pain population. DESIGN: A 12-month probabilistic simulation model was developed to estimate the reduction of misuse and/or abuse from a physician's prescribing decisions for 10,000 patients. Model inputs included probabilities for opioid misuse and/or abuse-related events, opioid discontinuation, and switching from ADO to non-ADO. Estimated reductions in abuse associated with ADOs were obtained from positive subjective measures using human abuse liability studies. The model was run separately for commercial, Medicare, Medicaid, and Veterans Administration (VA) populations. The difference in healthcare resource utilization and associated costs (2015 USD) between the ADO and non-ADO simulations was calculated. NNH for non-ADO was also calculated. RESULTS: Misuse and/or abuse-related events for patients prescribed ER non-ADOs ranged from 223-1,410 and associated costs ranged from $20-$98 per patient for commercial and Medicare populations, respectively. Prescribing ER ADOs were associated with 87, 289, 264, and 417 fewer misuse and/or abuse-related events, saving $8, $35, $21, and $29 per patient in commercial, VA, Medicaid, and Medicare populations, respectively. NNH ranged from 185 in the commercial population to 40 in the Medicare population. Results were sensitive to decreases in the probability of misuse and/or abuse events but showed reductions. CONCLUSIONS: A physician's decision to prescribe ER ADOs could lead to large reductions in misuse and/or abuse-related events and associated costs across many patient populations.

Long-term Systemic Corticosteroid Exposure: A Systematic Literature Review.

PURPOSE: While corticosteroids are relatively inexpensive and commonly used as treatment for a variety of conditions, long-term use is known to be associated with certain toxicities. Prior systematic reviews have revealed an increased risk for costly adverse events (AEs), including bone fracture, infection, and gastrointestinal bleeding. The objective of this study was to conduct a systematic literature review of recent publications on the burden of long-term corticosteroid exposure, specifically, to summarize the AEs and economic impact of long-term corticosteroid use and to reveal data gaps for additional research. METHODS: The Ovid search platform was used to access scientific literature databases. The search strategy targeted the use of corticosteroids and economic outcomes research. Articles were restricted to those published between 2007 and 2016 to cover publications since prior reviews; conference abstracts and articles assessing pediatrics were excluded. Titles and abstracts resulting from inclusion criteria were screened, and reviewers independently extracted relevant information from the relevant full-text articles. FINDINGS: The literature review included 32 articles, with 75% focusing on autoimmune diseases, asthma, or lung diseases. Included articles were 14 database analyses, 6 simulations, 6 clinical trials, 3 systematic literature reviews, 2 patient surveys, and 1 chart review. Commonly-cited AEs associated with long-term corticosteroid exposure included hypertension (prevalence >30%); bone fracture (21%-30%); cataract (1%-3%); nausea, vomiting, and other gastrointestinal conditions (1%-5%); and metabolic issues (eg, weight gain, hyperglycemia, and type 2 diabetes; cases had 4-fold the risk of controls). Association of dose and duration with increased AE risk is not well-quantified. AEs like peptic ulcer and myocardial infarction are particularly costly to payers (1-year cost of $21,825 and $26,472, respectively, in year-2009 USD). The few articles assessing the economic impact of corticosteroid use have found dose-related increases in health care resource utilization and costs, with per-annum incremental costs relative to nonusers ranging from $5700 in low-dose users (<7.5 mg/d) to $29,000 in high-dose users (>15 mg/d). Adherence to treatment guidelines on avoiding AEs (eg, prescribing of oral bisphosphonates, calcium, and vitamin D) remains low. IMPLICATIONS: Although doses of long-term corticosteroids have fallen over the past several decades in response to AEs, dose reduction may not be a sufficient solution. Numerous AEs, some very costly, persist among long-term corticosteroid users, suggesting a need for further research to fill current data gaps, as well as a potential need for alternative treatment options.

The burden of hepatorenal syndrome among commercially insured and Medicare patients in the United States.

BACKGROUND: This study evaluated the characteristics, healthcare resource utilization (HCRU), and costs, from the payer perspective, of hepatorenal syndrome (HRS) patients covered by commercial and Medicare insurance. Mortality was assessed as a secondary outcome. METHODS: Patients were identified from claims databases of commercially insured patients (OptumHealth Care Solutions Inc.) in 1998-2014 and Medicare beneficiaries in 2009-2013 (5% Standard Analytic Files). At the time of their first inpatient admission ("index date") with an HRS diagnosis (ICD-9 code 572.4), commercially insured patients must be aged 18-64 and Medicare patients must be aged 65 and older. RESULTS: A total of 784 commercially insured and 1061 Medicare HRS patients met the sample selection criteria. Patients were disproportionately male (commercial: 63.0%; Medicare: 57.9%) with a mean age of 54.1 among commercially insured and 74.1 among Medicare patients. Within the first 30 days, the average hospital length of stay (LOS) was 12.3 days among commercially insured and 10.8 days among Medicare patients. Based on Kaplan-Meier analyses, 36% of commercially insured and 26% of Medicare patients were readmitted within the next 30 days. During follow-up, many patients received dialysis (commercial: 33.0%; Medicare: 22.1%) or liver transplant (commercial: 10.7%; Medicare: 1.6%). Average costs within the 90 day follow-up were $157,665 for commercially insured and $48,322 for Medicare patients, with 68.3% and 78.3% of the costs incurred within the first 30 days. The primary cost driver was inpatient visits (commercial: 90.3% of costs; Medicare: 83.1% of costs), with differences between the populations consistent with lower mortality, higher dialysis rates, and higher transplant rates (both liver and kidney) among the commercially insured. Using US population and prevalence statistics, these results suggest that HRS imposes an annual total direct medical cost burden of approximately $3.0-$3.8 billion to payers over the period. CONCLUSIONS: HRS imposes a significant economic burden.

Positive subjective measures in abuse liability studies and real-world nonmedical use: Potential impact of abuse-deterrent opioids on rates of nonmedical use and associated healthcare costs.

OBJECTIVE: To quantify the potential impact of reductions in positive subjective measures from human abuse liability studies on real-world rates of nonmedical use of prescription drugs and associated healthcare resource utilization and costs. DESIGN: Positive subjective endpoints "overall drug liking," in-the-moment "drug liking," and "drug high" Emaxs (peak effects) were recorded from published studies. Nonmedical use data were obtained from the 2010 National Survey on Drug Use and Health (NSDUH) and Drug Abuse Warning Network surveys. Multivariate regressions evaluated the association between the positive subjective endpoints and nonmedical use rates, controlling for prescription volume, whether the drug is an opioid, and controlled substance schedule. A published budget-impact model was used to assess healthcare resource utilization and cost impacts of abuse-deterrent opioid formulations. RESULTS: A five-point reduction in overall drug liking/drug liking/drug high Emax was associated with a 0.25/0.10/0.05 (standard errors: 0.11/0.12/0.07) percentage point decrease in the NSDUH lifetime nonmedical use rates. Those decreases yielded a 11.3/4.2/2.1 percent reduction compared to the samples' lifetime nonmedical use rates of 2.21/2.38/2.36 percent. On the basis of a number of assumptions, these reductions were associated with private payer cost reductions for a morphine and oxycodone abuse-deterrent formulation in the ranges of $147.9-324.1 million and $230.7-958.7 million, respectively. CONCLUSIONS: Reductions in overall drug liking were significantly associated with reduced real-world nonmedical use, healthcare utilization, and costs. Associations using drug high and drug liking were directionally consistent with this finding though not statistically significant. A reduction in positive subjective measures associated with an abuse-deterrent formulation has potential to reduce abuse and associated healthcare utilization and costs.

Medical cost savings associated with an extended-release opioid with abuse-deterrent technology in the US.

OBJECTIVES: In the US, prescription opioids with technology designed to deter abuse have been introduced to deter drug abuse without hindering appropriate access for pain patients. The objective of this study was to estimate changes in medical costs following the introduction of a new formulation of extended-release (ER) oxycodone HCl (oxycodone) with abuse-deterrent technology in the US. METHODS: Health insurance claims data were used to estimate changes in rates of diagnosed opioid abuse among continuous users of extended-release opioids (EROs) following the introduction of reformulated ER oxycodone in August 2010. This study also calculated the excess medical costs of diagnosed opioid abuse using a propensity score matching approach. These findings were integrated with published government reports and literature to extrapolate the findings to the national level. All costs were inflated to 2011 US dollars. RESULTS: The introduction of reformulated ER oxycodone was associated with relative reductions in rates of diagnosed opioid abuse of 22.7% (p < 0.001) and 18.0% (p = 0.034) among commercially-insured and Medicaid patients, respectively. There was no significant change among Medicare-eligible patients. The excess annual per-patient medical costs associated with diagnosed opioid abuse were $9456 (p < 0.001), $10,046 (p < 0.001), and $11,501 (p < 0.001) for commercially-insured, Medicare-eligible, and Medicaid patients, respectively. Overall, reformulated ER oxycodone was associated with annual medical cost savings of ∼$430 million in the US. LIMITATIONS: Because of the observational research design of this study, caution is warranted in any causal interpretation of the findings. Portions of the study relied on prior literature, government reports, and assumptions to extrapolate the national medical cost savings. CONCLUSIONS: This study provides evidence that reformulated ER oxycodone has been associated with reductions in abuse rates and substantial medical cost savings. Payers and policy-makers should consider these benefits as they devise and implement new guidelines and policies in this therapeutic area.

Prescription opioid abuse: challenges and opportunities for payers.

OBJECTIVES: Prescription opioid abuse and addiction are serious problems with growing societal and medical costs, resulting in billions of dollars of excess costs to private and governmental health insurers annually. Although difficult to accurately assess, prescription opioid abuse also leads to increased insurance costs in the form of property and liability claims, and costs to state and local governments for judicial, emergency, and social services. This manuscript's objective is to provide payers with strategies to control these costs, while supporting safe use of prescription opioid medications for patients with chronic pain. METHOD: A Tufts Health Care Institute Program on Opioid Risk Management meeting was convened in June 2010 with private and public payer representatives, public health and law enforcement officials, pain specialists, and other stakeholders to present research and develop recommendations on solutions that payers might implement to combat this problem. RESULTS: While protecting access to prescription opioids for patients with pain, private and public payers can implement strategies to mitigate financial risks associated with opioid abuse, using internal strategies such as formulary controls, claims data surveillance, and claims matching; and external policies and procedures that support and educate physicians on reducing opioid risks among patients with chronic pain. CONCLUSIONS: Reimbursement policies, incentives, and health technology systems that encourage physicians to use universal precautions, to consult prescription monitoring program (PMP) data, and to implement Screening, Brief Intervention, and Referral to Treatment protocols have a high potential to reduce insurer risks while addressing a serious public health problem.

A model to identify patients at risk for prescription opioid abuse, dependence, and misuse.

OBJECTIVE: The objective of this study was to use administrative claims data to identify and analyze patient characteristics and behavior associated with diagnosed opioid abuse. DESIGN: Patients, aged 12-64 years, with at least one prescription opioid claim during 2007-2009 (n = 821,916) were selected from a de-identified administrative claims database of privately insured members (n = 8,316,665). Patients were divided into two mutually exclusive groups: those diagnosed with opioid abuse during 1999-2009 (n = 6,380) and those without a diagnosis for opioid abuse (n = 815,536). A logistic regression model was developed to estimate the association between an opioid abuse diagnosis and patient characteristics, including patient demographics, prescription drug use and filling behavior, comorbidities, medical resource use, and family member characteristics. Sensitivity analyses were conducted on the model's predictive power. RESULTS: In addition to demographic factors associated with abuse (e.g., male gender), the following were identified as "key characteristics" (i.e., odds ratio [OR] > 2): prior opioid prescriptions (OR = 2.23 for 1-5 prior Rxs; OR = 6.85 for 6+ prior Rxs); at least one prior prescription of buprenorphine (OR = 51.75) or methadone (OR = 2.97); at least one diagnosis of non-opioid drug abuse (OR = 9.89), mental illness (OR = 2.45), or hepatitis (OR = 2.36); and having a family member diagnosed with opioid abuse (OR = 3.01). CONCLUSIONS: Using medical as well as drug claims data, it is feasible to develop models that could assist payers in identifying patients who exhibit characteristics associated with increased risk for opioid abuse. These models incorporate medical information beyond that available to prescription drug monitoring programs that are reliant on drug claims data and can be an important tool to identify potentially inappropriate opioid use.