Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Economic and Humanistic Burden Among Medicare-Aged Women With Fragility Fracture in the United States.

OBJECTIVE: Describe patient characteristics, health care resource utilization, costs, and humanistic burden of women with Medicare insurance with incident fragility fracture who were admitted to post-acute-care (PAC). DESIGN: Retrospective cohort study using 100% Medicare Fee-for-Service (FFS) data. SETTING AND PARTICIPANTS: Community-dwelling female Medicare beneficiaries with incident fragility fracture January 1, 2017, to October 17, 2019, resulting in PAC admission to a skilled nursing facility (SNF), home-health care, inpatient-rehabilitation facility, or long-term acute-care hospital. METHODS: Patient demographic/clinical characteristics were measured during 1-year baseline. Resource utilization and costs were measured during baseline, PAC event, and PAC follow-up. Humanistic burden was measured among SNF patients with linked Minimum Data Set assessments. Multivariable regression examined predictors of PAC costs after discharge and changes in functional status during SNF stay. RESULTS: A total of 388,732 patients were included. Compared with baseline, hospitalization rates were 3.5, 2.4, 2.6, and 3.1 times higher and total costs 2.7, 2.0, 2.5, and 3.6 times higher for SNF, home-health, inpatient-rehabilitation, and long-term acute-care, respectively, following PAC discharge. Utilization of dual-energy X-ray absorptiometry (DXA) and osteoporosis medications remained low: 8.5% to 13.7% received DXA during baseline vs 5.2% to 15.6% following PAC; 10.2% to 12.0% received osteoporosis medication during baseline vs 11.4% to 22.3% following PAC. Dual eligibility for Medicaid (ie, low income) was associated with 12% higher costs; Black patients had 14% higher costs. Activities of daily living scores improved 3.5 points during SNF stay, but Black patients had 1.22-point lower improvement than White patients. Pain intensity scores showed small improvement (-0.8 points). CONCLUSIONS AND IMPLICATIONS: Women admitted to PAC with incident fracture had high humanistic burden with little improvement in pain and functional status and significantly higher economic burden after discharge compared with baseline. Disparities in outcomes related to social risk factors were observed, with consistently low utilization of DXA and osteoporosis medications even after fracture. Results indicate a need for improved early diagnosis and aggressive disease management to prevent and treat fragility fractures.

Real-world evidence: new opportunities for osteoporosis research. Recommendations from a Working Group from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research. PURPOSE: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated. METHODS: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice. RESULTS: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research. CONCLUSIONS: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings.

Potential drug-drug and drug-condition interactions among fibromyalgia patients initiating pregabalin or duloxetine: prevalence and health care expenditure impact.

OBJECTIVE: To quantify the prevalence of potential drug-drug/drug-condition interactions (DDI/DCI) among fibromyalgia patients initiating pregabalin or duloxetine, and to determine the impact of potential DDI/DCI on health care expenditures. DESIGN: Retrospective cohort study. SETTING: U.S. clinical practice, as reflected within a large administrative claims database. SUBJECTS: Fibromyalgia patients newly initiating pregabalin or duloxetine between July 1, 2008 and October 1, 2010 (initiation date = index). OUTCOME MEASURES: Potential DDI measured using clinical software that identifies co-prescription of medications that potentially interact with pregabalin or duloxetine. Potential DCI, drawn from the contraindications and warnings and precautions sections of pregabalin and duloxetine prescribing information, measured using administrative claims-based algorithms. All-cause health care expenditures measured throughout a 6-month postindex period. Analyses included univariate, bivariate, and multivariable statistical approaches. RESULTS: Seven thousand seven hundred fifty-one pregabalin and 7,785 duloxetine initiators were selected for study: mean age 49 years, 88% female. Only 1.4% of pregabalin initiators had ≥1 potential pregabalin DCI; none had potential pregabalin DDI. In contrast, 67% of duloxetine initiators had potential duloxetine DDI/DCI, driven mostly by potential duloxetine DDI (62% of duloxetine initiators). Compared between pregabalin and duloxetine initiators, differences in the prevalence of potential DDI/DCI were statistically significant (P < 0.001). Multivariable analyses indicated that, among duloxetine initiators, those with potential duloxetine DDI/DCI had postinitiation health care expenditures that were $670 higher (P < 0.001) than those without potential duloxetine DDI/DCI. Among pregabalin initiators, potential pregabalin DDI/DCI were not associated with health care expenditures. CONCLUSIONS: Among fibromyalgia patients initiating pregabalin or duloxetine, potential duloxetine DDI could be highly prevalent. Among duloxetine initiators, potential duloxetine DDI/DCI were significantly associated with increased health care expenditures.

Cost comparison of drug-drug and drug-condition interactions in patients with painful diabetic peripheral neuropathy treated with pregabalin versus duloxetine.

PURPOSE: The frequency and financial impact of potential drug-drug interactions (DDIs) and drug-condition interactions (DCIs) in patients with painful diabetic peripheral neuropathy (DPN) treated with either pregabalin or duloxetine were compared. METHODS: This retrospective cohort study was conducted using a large U.S. administrative claims database. Patients selected for study inclusion had a diagnosis of DPN and were newly initiated on either pregabalin or duloxetine between July 1, 2008, and October 1, 2010. Data on potential DDIs and DCIs were collected. Health care costs were measured as the sum of gross covered payments for all medical and prescription claims incurred during the six months after the index date. RESULTS: The study sample comprised 2499 pregabalin users and 1354 duloxetine users. Among pregabalin users, 48 (1.8%) had at least one potential pregabalin DCI; none had potential pregabalin DDIs. Among duloxetine users, 966 (71%) had at least one potential duloxetine DDI or DCI. The frequencies of potential DDIs and DCIs differed significantly between pregabalin and duloxetine users (p < 0.001). Potential duloxetine DDIs and DCIs were associated with a significant increase in mean health care costs in duloxetine users (p = 0.002). Potential pregabalin DDIs and DCIs were not associated with additional health care costs in pregabalin users. CONCLUSION: Among patients with painful DPN treated with either pregabalin or duloxetine, the frequency of potential duloxetine DDIs and DCIs was substantially higher than that of pregabalin. Potential DDIs and DCIs were associated with significantly increased health care costs in duloxetine users.

The impact of 'best-practice' patient care in fibromyalgia on practice economics.

OBJECTIVE: The office time required for primary care physicians (PCPs) to diagnose, treat and manage fibromyalgia (FM) patients can be extensive. The study objective was to determine if PCPs can positively impact practice economics by requiring fewer patient visits and less office time, while still achieving an acceptable quality of life, as reported by the physician. STUDY DESIGN: Survey of PCPs who diagnose, manage and treat FM patients. METHODS: Surveys were administered to US private practice PCPs, obtaining information on the number of office visits, and time spent with FM patients. PCPs were allotted into two groups: FM-efficient (FME; n = 40) and FM usual care (FMUC; n = 54), based on their reported ability to achieve an acceptable quality of life for ≥50% of their FM patients in less than four office visits post FM diagnosis. An economic model estimated the monetary value of each PCP cohorts' time spent with a newly diagnosed FM patient over a 2-year timeframe. RESULTS: Significant office time cost differences across 2 years exist between FME PCPs and FMUC PCPs ($840 vs. $1117, P < 0.05). FME PCPs had a significantly lower cost of scheduled time to confirm diagnosis ($243 vs. $339, P < 0.05) and time to find right treatment ($264 vs. $365, P < 0.05) than FMUC PCPs. Both groups incurred costs related to excess visit time, but it was less for FME PCPs ($119, 29 minutes) than FMUC PCPs ($182, 44 minutes, P < 0.01), driven by quicker diagnosis confirmation (P < 0.01) and treatment initiation (P < 0.01). CONCLUSIONS: Research suggests that efficient FM care delivery during diagnosis and treatment can be associated with improved practice economics.

Real-world evaluation of health-care resource utilization and costs in employees with fibromyalgia treated with pregabalin or duloxetine.

OBJECTIVE: To evaluate changes in health-care resource use and costs after initiating pregabalin or duloxetine in employees with fibromyalgia (FM). METHODS: Employees (18 to 64 years old) with at least one claim for an FM-attributable medication within 60 days following an FM diagnosis were identified using the Thomson Reuters MarketScan(®) Commercial Database (2006 to 2008). Patients newly initiated on pregabalin were propensity score matched to patients newly initiated on duloxetine. These treatment cohorts were evaluated for changes between the 6-month pre- and post-initiation periods in health-care utilization including prescriptions, imputed medically related work loss and expenditures. Pre- to post-initiation changes were compared between pregabalin and duloxetine using a difference-in-difference approach based on univariate statistics and multivariable models. RESULTS: A total of 731 employees with FM initiated on pregabalin (89.9% female, mean age 47.1±9.7 years) were matched with 731 employees initiated on duloxetine (89.5% female, mean age 47.1±9.8 years); other demographic and clinical characteristics were also comparable between cohorts. The adjusted marginal effects were not statistically significant for pre- to post-changes in opioid utilization (P=0.856), number of FM-attributable (P=0.151) or FM-related medications (P=0.462), and all-cause (P=0.323) or FM-attributable (P=0.991) expenditures. Pregabalin was associated with a significantly lower probability of any medically related work loss of 3.2 percentage points (P=0.030) compared with duloxetine, but changes in indirect costs were not significantly different (P=0.600). CONCLUSIONS: The changes in health resource utilization and costs after initiation of pregabalin were not significantly different than the changes observed after initiation of duloxetine. These results not only demonstrate an overall similarity of resource utilization, but also suggest cost neutrality between pregabalin and duloxetine.

Evaluation of healthcare resource utilization and costs in employees with pain associated with diabetic peripheral neuropathy treated with pregabalin or duloxetine.

OBJECTIVE: To evaluate changes in healthcare resource use and costs after initiating pregabalin or duloxetine in employees with pain associated with diabetic peripheral neuropathy (pDPN). METHODS: Employees (18-64 years old) with a DPN diagnosis and at least one pDPN-related pain medication claim were identified using the MarketScan Commercial Database (2005-2008). Propensity scored matched pregabalin and duloxetine new starts were evaluated in the 6-month pre- and 6-month post-initiation periods. Study outcomes including imputed medically-related work loss, prescription and healthcare utilization, and associated expenditures were analyzed using univariate statistics and multivariate models in a difference-in-difference approach. RESULTS: A total of 473 employees in each treatment group were identified. Mean age was 53.6 (SD 7.0) years for pregabalin and 53.5 (SD 7.4) years for duloxetine. There were no pre-index differences between groups. Adjusted marginal effects were not statistically significant for pre-to-post changes in opioid utilization (p = 0.328), number of pDPN-related analgesic medications (p = 0.506), all-cause healthcare costs (p = 0.895), indirect costs (p = 0.324), or pDPN-attributable expenditures (p = 0.359). LIMITATIONS: Claims analysis is limited in accounting for all patient and plan differences, and by the reliability of medical claims for diagnosis coding. The sample size of the matched cohorts may have limited the power of the analysis to detect differences. CONCLUSIONS: There were no significant pre-to-post differences between pregabalin and duloxetine treatment groups in pDPN-related analgesic medication use, or pDPN-attributable, all-cause, and indirect expenditures.

The utility and limitations of FRAX: A US perspective.

The FRAX calculator is a major achievement in terms of our understanding of measuring fracture risk. Along with being an easily accessible web-based tool, it is the only model based on extensive data on multiple cohorts. FRAX will help clinicians identify individuals who need osteoporosis treatments, while also screening out those who do not require osteoporosis treatments. However, FRAX is limited by a number of factors. Although it is web based, few physicians have the means to access it. It also assumes that body mass index and mortality are constant across different racial and ethnic groups. FRAX is further limited by the exclusion of variables known to be associated with fracture risk, lack of dose-response relationships for variables, increased subsequent fracture risk after initial fracture, restriction to only one bone mineral density site, racial and ethnic differences that may influence fracture risk, and availability of racial and ethnic fracture risk data to be used in the FRAX calculator. Finally, the values obtained from FRAX should not take the place of good clinical judgment.

Burden of fibromyalgia and comparisons with osteoarthritis in the workforce.

OBJECTIVES: To calculate the fibromyalgia (FM) burden of illness (BOI) from the employer perspective and to compare annual prevalence, work output, absence, and health benefit costs of employees with FM versus osteoarthritis (OA). METHODS: Retrospective regression model analysis comparing objective work output, total health benefit (health care, prescription drug, sick leave, disability, workers' compensation) costs, and absence days for FM, versus OA and NoFM cohorts, while controlling for differences in patient characteristics. RESULTS: FM prevalence was 0.73%; OA 0.90%. Total health benefit costs for FM were $8452 versus $11,253 (P < 0.0001) for OA and $4013 (P < 0.0001) for NoFM, with BOI = $4439. Total absence days were 16.8 versus 19.8 (P < 0.0001) and 6.4 (P < 0.0001), respectively. FM had significantly lower annual work output than NoFM (19.5%, P = 0.003) but comparable with OA. CONCLUSION: FM places a significant cost, absence, and productivity burden on employers.

Methodological considerations in using claims databases to evaluate persistence with bisphosphonates for osteoporosis.

OBJECTIVE: To demonstrate that retrospective analyses of medication persistence require careful methodological approaches to assure accuracy and consistency across various types of databases. Bisphosphonates (BPs) are used as an example because of the availability of diverse dosing options that can create a unique set of challenges for persistence analyses. METHODS: Reports of BP persistence were compared for methodological approaches, including data source, duration of follow-up, allowed gap for persistence, and presentation of results. MAIN OUTCOME MEASURES: Medication persistence. RESULTS: Comparisons among reports of BP persistence for weekly and monthly formulations revealed inconsistent definitions and a variety of methods. Persistence analyses varied greatly, particularly in allowed gaps and adjustment for demographic and clinical characteristics that affected results. Persistence with weekly dosing was 179-249 days, with 24-78% remaining on treatment at 1 year. Analyses of persistence with monthly treatment was complicated by the variety of gap lengths (30-90 days). The studies reviewed had many limitations, including lack of an established threshold for efficacy, inadequacy of information in databases, and potential biases in case selection (treatment-naive or experienced). CONCLUSIONS: The limitations of published studies reveal the need for a more consistent approach to medication persistence analyses using claims databases to allow for comparison across reports. The analysis plan should present definitions of all terms, details of all methods and types of adjustments needed for demographic and clinical characteristics, as well as specify allowed gaps between refills. These approaches would improve clinical utility of data describing BP persistence and its impact on fracture risk.

An evaluation of patient preferences for osteoporosis medication attributes: results from the PREFER-US study.

OBJECTIVE: To evaluate preferences for eight medication attributes that women may consider when evaluating prescription osteoporosis medications. RESEARCH DESIGN AND METHODS: The eligible sample consisted of women aged 50 years or older who responded to the 2003 or 2004 Internet-based National Health and Wellness Survey as being diagnosed with osteoporosis, considering themselves at risk, or having a family history of osteoporosis. In this Internet survey (the PREFER survey), respondents were asked to: (1) force-rank order the eight attributes from one to eight according to their preferences and (2) separately rate the importance of each attribute on a Likert-type scale from 1 (extremely unimportant) to 7 (extremely important). RESULTS: We collected 999 responses across 3 days from a sample of 3368 women and stopped compiling responses after achieving sample size targets. Drug effectiveness (e.g., ability to reduce the risk of fractures) was force ranked as the No. 1 preferred osteoporosis medication attribute by 37% of the sample. Side effects were force ranked as the No. 1 preferred medication attribute by 36% of the sample. Dosing frequency, dosing procedure, and formulation (i.e., how the drug is taken) were each force ranked as No. 1 by 2% or less of the sample. Drug effectiveness had the highest percentage of 'extremely important' responses (59%) followed by drug interactions (53%). Drug effectiveness was the highest-rated attribute (mean [S.D.] = 6.1 [1.6], median = 7), while dosing frequency was the lowest-rated attribute (mean [S.D.] = 4.7 [1.8], median = 5). CONCLUSIONS: In our sample of women with a diagnosis of osteoporosis or at risk for osteoporosis, drug effectiveness was the most highly ranked and rated of eight osteoporosis medication attributes. Side effects and drug interactions were also highly ranked and rated. Healthcare providers should consider incorporating patient preferences for key medication attributes into their therapeutic decision-making processes.

Quality-of-life issues in osteoporosis.

Osteoporosis is responsible for more than 1.5 million fractures per year in the United States including vertebral and nonvertebral fractures of the hip and wrist. Most of the impact of osteoporosis on quality of life relates to fracture. While the morbidity and mortality of hip fractures have long been recognized, only recently have we also recognized the significant burden of vertebral fractures. With the development of generic and disease targeted quality-of-life instruments we have now confirmed observational studies showing that clinical vertebral fractures have significant effects on quality of life. The economic burden of vertebral fractures, if we include direct and indirect costs, may be similar to hip fractures. The relative risk for mortality after clinical vertebral fracture is at least equivalent to that of hip fracture. The burden of vertebral fractures relates not only to pain but also to kyphosis. Because vertebral fractures are often under diagnosed and under treated, these findings are a call to action because the first vertebral fracture leads to significantly increased risk for subsequent vertebral and osteoporotic fracture with further loss of quality of life.