Economic and Humanistic Burden of Moderate and Severe Hemophilia A and B in Spain: Real-World Evidence Insights from the CHESS II Study.

Background: Hemophilia is a congenital disorder characterized by deficiency or absence of clotting factor VIII in hemophilia A (HA) or clotting factor IX in hemophilia B (HB), resulting in frequent, repeated, and prolonged spontaneous or traumatic bleeding into joints or soft tissue. Severity is classified by the patient's baseline level of clotting factor activity as mild (>5%-40%), moderate (1%-5%), or severe (<1%). In Spain, there is limited information on the societal economic burden of disease. Objective: To estimate the economic and humanistic burden of disease in adult patients with non-inhibitor moderate and severe HA and HB in Spain. Methods: Spanish data from the CHESS II study (2018-2020) on patients' clinical characteristics, health-related quality of life (HRQoL) and hemophilia-related healthcare resource utilization were analyzed. Economic burden was determined by estimating condition-related annual per-patient direct (medical and nonmedical) and indirect costs, stratified according to hemophilia type and severity and presented as 2022 Euros. HRQoL was assessed via the EQ-5D-5L. Results: Of 341 patients in the Spanish CHESS II cohort, 288 patients met the inclusion criteria: 181 had HA (37% [n = 66] moderate and 63% [n=115] severe) and 107 had HB (26% [n = 28] moderate and 74% [n = 79] severe). Mean annual direct cost was higher in HB than in HA, and higher in severe than in moderate patients, resulting in an annual cost/patient of €17 251 (moderate HA), €17 796 (moderate HB), €116 767 (severe HA) and €206 996 (severe HB). The main direct cost component in all groups except moderate HA was factor replacement therapy. Mean per-patient indirect cost was €4089 (moderate HA), €797 (moderate HB), €8633 (severe HA) and €8049 (severe HB). Finally, the mean total cost (direct and indirect) for moderate and severe patients were €91 017 (HA) and €163 924 (HB). EQ-5D-5L [SD] scores were lower in patients with severe HA (0.77 [0.18]) and severe HB (0.70 [0.22]) compared with patients with moderate HA (0.81 [0.15]) and moderate HB (0.86 [0.17]). Conclusions: Independently of the type of hemophilia, greater condition severity was associated with increased costs and a decrease in HRQoL.

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

BACKGROUND: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. MATERIALS AND METHODS: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. RESULTS: Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). CONCLUSION: OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

Racial variation in healthcare resource utilization and expenditures in knee/hip osteoarthritis patients: a retrospective analysis of a Medicaid population.

BACKGROUND: Osteoarthritis (OA) is a leading cause of chronic pain and disability. Prior studies have documented racial disparities in the clinical management of OA. The objective of this study was to assess the racial variations in the economic burden of osteoarthritis within the Medicaid population. METHODS: We conducted a retrospective observational study using the MarketScan Multi-State Medicaid database (2012-2019). Newly diagnosed, adult, knee and/or hip OA patients were identified and followed for 24 months. Demographic and clinical characteristics were collected at baseline; outcomes, including OA treatments and healthcare resource use (HCRU) and expenditures, were assessed during the 24-month follow-up. We compared baseline patient characteristics, use of OA treatments, and HCRU and costs in OA patients by race (White vs. Black; White vs. Other) and evaluated racial differences in healthcare costs while controlling for underlying differences. The multivariable models controlled for age, sex, population density, health plan type, presence of non-knee/hip OA, cardiovascular disease, low back pain, musculoskeletal pain, presence of moderate to severe OA, and any pre-diagnosis costs. RESULTS: The cohort was 56.7% White, 39.9% Black and 3.4% of Other race (American Indian/Alaska Native, Hispanic, Asian, Native Hawaiian/Other Pacific Islander, two or more races and other). Most patients (93.8%) had pharmacologic treatment for OA. Inpatient admission during the 24-month follow-up period was lowest among Black patients (25.8%, p < .001 White vs. Black). In multivariable-adjusted models, mean all-cause expenditures were significantly higher in Black patients ($25,974) compared to White patients ($22,913, p < .001). There were no significant differences between White patients and patients of Other race ($22,352). CONCLUSIONS: The higher expenditures among Black patients were despite a lower rate of inpatient admission in Black patients and comparable length and number of hospitalizations in Black and White patients, suggesting that other unmeasured factors may be driving the increased costs among Black OA patients.

Higher healthcare costs were observed in Black Medicaid patients with knee/hip osteoarthritis despite lower rates of inpatient admission. We observed these differences in this Medicaid population, where socioeconomic status is more homogeneous.Black patients had significantly higher healthcare costs compared to White patients and the difference persisted even after accounting for underlying differences in Black and White patients.Higher healthcare costs among Black patients were found in both the baseline and follow-up periods overall for all types of healthcare (hospitalizations, ER, office visit, other services).Higher hospitalization costs in Black patients were observed despite lower rates of hospitalizations in Black patients. These increased costs cannot be attributed to either longer or more frequent hospitalizations; no significant difference in either the length of stay or the number of hospitalizations was observed when comparing Black patients to White patients.

Prescription opioid utilization patterns, and associated outcomes, among privately insured patients prescribed opioids to manage pain associated with osteoarthritis.

OBJECTIVE: To describe utilization patterns, negative clinical outcomes and economic burden of patients diagnosed with osteoarthritis (OA) of the hip and/or knee who received a prescription for tramadol or non-tramadol opioids vs. non-opioid drugs. METHODS: Optum Healthcare Solutions, Inc. commercial claims data were used (1/2012--3/2017). Adults with ≥2 diagnoses of OA of the hip and/or knee, and ≥30 days supply of pain medications were identified during the three-year period from the date of first prescription (index date) after the first OA diagnosis. Drug utilization statistics in the follow-up period were summarized by initial treatment (i.e. tramadol, non-tramadol opioids, non-opioid drugs). Opioid initiators were matched to those initiated on non-opioid treatments using a propensity score model accounting for baseline characteristics. Matched pairs analysis compared outcomes for these cohorts. RESULTS: Of 62,715 total patients, 15,270 (24.3%) initiated treatment with opioids, including 3,513 (5.6%) on tramadol and 11,757 (18.7%) on non-tramadol opioids. Opioid initiators had more comorbidities, higher baseline healthcare costs, and were more likely to have OA of the hip. Among non-opioid initiators, 27.5% switched to tramadol and 63% switched to non-tramadol opioids. Among tramadol initiators, 71% switched to non-tramadol opioids. Patients initiated on opioids had 20.4% (p < .01) higher all-cause healthcare costs and higher percentages experiencing multiple negative clinical outcomes (all p < .01) compared to matched controls. CONCLUSIONS: Most patients with OA of the hip and/or knee either initiate on or switch to opioids for long-term management of OA-related pain despite known risks. This highlights the need for new treatments that delay or prevent use of opioids.

Use of electronic health data to identify patients with moderate-to-severe osteoarthritis of the hip and/or knee and inadequate response to pain medications.

BACKGROUND: No algorithms exist to identify important osteoarthritis (OA) patient subgroups (i.e., moderate-to-severe disease, inadequate response to pain treatments) in electronic healthcare data, possibly due to the complexity in defining these characteristics as well as the lack of relevant measures in these data sources. We developed and validated algorithms intended for use with claims and/or electronic medical records (EMR) to identify these patient subgroups. METHODS: We obtained claims, EMR, and chart data from two integrated delivery networks. Chart data were used to identify the presence or absence of the three relevant OA-related characteristics (OA of the hip and/or knee, moderate-to-severe disease, inadequate/intolerable response to at least two pain-related medications); the resulting classification served as the benchmark for algorithm validation. We developed two sets of case-identification algorithms: one based on a literature review and clinical input (predefined algorithms), and another using machine learning (ML) methods (logistic regression, classification and regression tree, random forest). Patient classifications based on these algorithms were compared and validated against the chart data. RESULTS: We sampled and analyzed 571 adult patients, of whom 519 had OA of hip and/or knee, 489 had moderate-to-severe OA, and 431 had inadequate response to at least two pain medications. Individual predefined algorithms had high positive predictive values (all PPVs ≥ 0.83) for identifying each of these OA characteristics, but low negative predictive values (all NPVs between 0.16-0.54) and sometimes low sensitivity; their sensitivity and specificity for identifying patients with all three characteristics was 0.95 and 0.26, respectively (NPV 0.65, PPV 0.78, accuracy 0.77). ML-derived algorithms performed better in identifying this patient subgroup (range: sensitivity 0.77-0.86, specificity 0.66-0.75, PPV 0.88-0.92, NPV 0.47-0.62, accuracy 0.75-0.83). CONCLUSIONS: Predefined algorithms adequately identified OA characteristics of interest, but more sophisticated ML-based methods better differentiated between levels of disease severity and identified patients with inadequate response to analgesics. The ML methods performed well, yielding high PPV, NPV, sensitivity, specificity, and accuracy using either claims or EMR data. Use of these algorithms may expand the ability of real-world data to address questions of interest in this underserved patient population.

The Burden of Metastatic Cancer-Induced Bone Pain: A Narrative Review.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer-induced bone pain and the effect of treatment of painful bone metastases on the patient's quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients' quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.

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.

A Retrospective Claims-Based Study Evaluating Clinical and Economic Burden Among Patients With Moderate to Severe Osteoarthritis Pain in the United States.

Background: There has been limited evaluation of medication adherence, healthcare resource utilization (HCRU), and healthcare costs over time in patients with osteoarthritis (OA), and stratification by pain severity level has not been reported. Assessing such longitudinal changes may be useful to patients and healthcare providers for tracking disease progression, informing treatment options, and employing strategies to optimize patient outcomes. Objectives: To characterize treatment patterns, HCRU, and costs over time in patients with moderate to severe (MTS) OA pain in the United States. Methods: We conducted a retrospective claims analysis, using IBM® MarketScan® databases, from 2013-2018. Eligible patients were aged ≥45 years with ≥12 months pre-index (baseline) and ≥24 months (follow-up) of continuous enrollment; index date was defined as a physician diagnosis of hip or knee OA. An algorithm was employed to identify MTS OA pain patients, who were propensity score matched with patients having non-MTS OA pain. Data were summarized using descriptive statistics and univariate analyses. Results: After propensity score matching, the overall OA pain cohorts consisted of 186 374 patients each: 61% were female, mean age was 63 years, and two-thirds (65.6%) were of working age (45-65 years). Sleep-related conditions, anxiety, and depression were significantly higher in the MTS OA pain cohort vs non-MTS (P<0.001). At baseline and 12- and 24-month follow-ups, receipt of prescription pain medications, HCRU, and direct medical costs were significantly higher in the MTS OA pain cohort (all P<0.01). Medication adherence was significantly higher in the MTS OA pain cohort for all medication classes except analgesics/antipyretics, which were significantly lower vs the non-MTS OA pain cohort (all P<0.0001). Conclusions: The burden of MTS OA pain is substantial, with patterns that show increasing medication use, HCRU, and costs vs non-MTS OA pain patients over time. Understanding the heterogeneity within the OA population may allow us to further appreciate the true burden of illness for patients in pain.

A Retrospective Cohort Analysis of the Impact of Osteoarthritis on Disability Leave, Workers' Compensation Claims, and Healthcare Payments.

OBJECTIVES: Examine short-term disability (STD) and workers' compensation (WC) associated leave and wage replacements, and overall direct healthcare payments, among employees with osteoarthritis (OA) versus other chronically painful conditions; quantifying the impact of opioid use. METHODS: Analysis of employees with more than or equal to two STD or WC claims for OA or pre-specified chronically painful conditions (control) in the IBM MarketScan Research Databases (2014 to 2017). RESULTS: The OA cohort (n = 144,355) had an estimated +1.2 STD days, +$152 STD payments, and +$1410 healthcare payments relative to the control cohort (n = 392,639; P < 0.001). WC days/payments were similar. Differences were partially driven by an association between opioid use, increased STD days/payments, and healthcare payments observed in pooled cohorts (P < 0.001). CONCLUSIONS: OA is associated with high STD days/payments and healthcare payments. Opioid use significantly contributes to these and this should be considered when choosing treatment.

Moderate to Severe Osteoarthritis Pain and Its Impact on Patients in the United States: A National Survey.

PURPOSE: Osteoarthritis (OA) is one of the most common causes of chronic pain and a leading cause of disability in the US. The objective of this study was to examine the clinical and economic burden of OA by pain severity. PATIENTS AND METHODS: We used nationally representative survey data. Adults ≥18 years with self-reported physician-diagnosed OA and experiencing OA pain were included in the study. OA pain severity was measured using the Short Form McGill Pain Questionnaire Visual Analog Scale (SF-MPQ-VAS). Data were collected for demographics, clinical characteristics, health-related quality of life (HRQoL), productivity, OA treatment, adherence to pain medication, and healthcare resource utilization. Univariate analysis was performed to examine differences between respondents with moderate-to-severe OA pain vs those with mild OA pain. RESULTS: Higher proportions of respondents with moderate-to-severe OA pain (n=3798) compared with mild OA pain (n=2038) were female (69.4% vs 57.3%), <65 years of age (54.8% vs 43.4%), and not employed (70.6% vs 64.5%). Respondents with moderate-to-severe OA pain experienced OA pain daily (80.8% vs 48.8%), were obese (53.0% vs 40.5%), had more comorbidities (sleep disturbance, insomnia, depression, and anxiety), and reported significantly poorer health status and HRQoL, and greater productivity and activity impairment (all P<0.05). Moderate-to-severe OA pain respondents were prescribed significantly more pain medications than mild OA pain respondents (41.0% vs 17.0%) and had higher adherence (75.9% vs 64.1%) yet were less satisfied with their pain medications (all P<0.001). Outpatient and emergency room visits, and hospitalizations in the 6 months prior to the survey were significantly higher in moderate-to-severe OA pain respondents vs those with mild OA pain (all P<0.05). CONCLUSION: Patient and clinical burden was significantly greater in moderate-to-severe OA pain respondents vs mild OA pain respondents and may inform decision-making for appropriate resource allocation and effective management strategies that target specific subgroups.