Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Cost-effectiveness Analysis of Sequential Treatment of Abaloparatide Followed by Alendronate Versus Teriparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis in the United States.

BACKGROUND: The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO. OBJECTIVE: To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States. METHODS: A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. RESULTS: Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance: ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

CLINICAL EVALUATION OF COST EFFICACY OF DRUGS FOR TREATMENT OF OSTEOPOROSIS: A META-ANALYSIS.

OBJECTIVE: To assess the cost efficacy of available regimens for therapy of osteoporosis as defined as the cost time's number need to treat to prevent one fracture. METHODS: Existing meta-analyses were supplemented through electronic databases SCOPUS and PubMed between 2013 (a date overlapping the latest meta-analyses) and March 2016. Primary references included all randomized controlled trials of anti-osteoporotic drugs versus comparators using search terms "osteoporosis," "random," and "trial." RESULTS: There were 43 evaluable randomized, double-blind, placebo-controlled trials in 71,809 postmenopausal women comparing fracture frequency. Trials were similar in recruitment age (mean ± SD, 67.3 ± 8.1 years) and follow-up duration (25.5 ± 12.6 months). Cost comparisons were evaluated for a treatment strategy assuming generic alendronate as first-line therapy. Denosumab and teriparatide showed benefits in vertebral fracture reduction over alendronate at incremental costs respectively of $46,000 and $455,000 per fracture prevented. Zoledronate, recently released as a generic, would be either less expensive or comparable in cost. None of the alternate medicines were statistically better in preventing hip fractures. Teriparatide was more effective in preventing nonvertebral fractures at an incremental cost of $1,555,000. CONCLUSION: The most cost-effective initial therapy of postmenopausal osteoporosis is generic oral alendronate or generic parenteral zoledronate. There is no statistically significant difference in efficacy of available drugs to prevent hip fractures. There are limited data to suggest switching drugs after sustaining an osteoporotic fracture while on oral alendronate therapy, although generic zoledronate may be considered on the basis of side effects or questions of medication adherence. ABBREVIATIONS: ALN = alendronate; DEN = denosumab; IBN = ibandronate; NNT = number needed to treat; OR = odds ratio; RCT = randomized controlled trial; RIS = risedronate; RLN = raloxifene; TER = teriparatide; ZOL = zoledronate.

Real-world clinical and economic outcomes for daily teriparatide patients in Japan.

A large medical and pharmacy claims database was used to evaluate outcomes in daily teriparatide (D-TPD) patients in Japan. 445 patients were identified (April 2008-July 2013) with 6+ months' pre- and 18+ months' post-index observation. D-TPD 20 µg subcutaneous injection is indicated for individuals at high risk of fracture. Descriptive analyses were conducted on clinical fractures, health care utilization, and costs. Adherence was measured by medication possession ratio (MPR) (High MPR > 0.8; 0.5 ≤ Medium MPR ≤ 0.8, Low MPR < 0.5). Adjusted analyses of Lower (Low + Medium) MPR vs. High MPR for fracture incidence and hospital admissions were performed using logistic and Poisson regression models; adjusted cost analyses used propensity bin bootstrapping methods. Baseline characteristics were: mean 74.7 years (standard deviation = 8.9); 90 % female; 20 % 1+ fracture. Post-index, 249 and 196 patients had High and Lower MPR, respectively. Mean incident fractures/1000 patient-years for Lower and High MPR patients were 77.4 and 57.7, respectively. Adjusted fracture risk was greater in Lower MPR patients [logistic odds ratio (OR) = 1.67, 95 % confidence interval 0.791-3.541; Poisson incidence rate ratio (IRR) = 1.505, 0.764-2.966]. Hospital admission risk was significantly greater in Lower than High MPR patients (OR = 1.85, 1.169-2.921; IRR = 1.47, 1.137-1.904). High MPR patients had numerically lower inpatient and total unadjusted costs than Lower MPR patients. Adjusted inpatient costs were significantly less in High MPR patients; outpatient and pharmacy costs were greater. Better adherence to D-TPD revealed a trend towards lower fracture risk, and significant reductions in hospital admissions and costs. The small sample size limited the robustness of these results.

Teriparatide use during an economic crisis: baseline data from the Greek cohort of the Extended Forsteo Observational Study (ExFOS).

BACKGROUND: The Extended Forsteo Observational Study (ExFOS) is a multinational, non-interventional, prospective, observational study that aims to provide real-life data on patients with osteoporosis treated with teriparatide for up to 24 months. It includes the new indications of osteoporosis in men and glucocorticoid-induced osteoporosis (GIOP). We describe the Greek subpopulation enrolled in this study and compare it with a similar cohort from the previous European Forsteo Observational Study (EFOS). METHODS: Baseline data were collected from the Greek cohort of ExFOS. Data included demographic characteristics, medical and osteoporosis history, disease status, prior use of medications, back pain and quality of life. RESULTS: Baseline data for 439 patients, enrolled at 31 sites, indicated the majority of patients were females (92.3%), elderly [mean (standard deviation; SD) age 70.1 (9.8) years] and slightly overweight [mean (SD) body mass index 26.7 (4.3) kg/m(2)], with very low bone mineral density (mean T-score <-3 in lumbar spine or total hip) and at least one previous fracture (55.1% of patients). Of the 439 patients, 19.8% were osteoporosis treatment naïve, 88.4% had experienced back pain during the previous 12 months, 68.1% had experienced back pain at least fairly often during the previous month and 50.9% reported moderate to severe limitation of activities due to back pain, with a mean (SD) of 4.2 (7.7) days spent in bed because of back pain during the previous month. Most baseline characteristics were numerically similar between the female ExFOS and EFOS cohorts; however, the rate of enrolment was faster in ExFOS (by approximately 45%) and a history of fracture was recorded in 53.8% of female patients in ExFOS versus 74.5% in EFOS. CONCLUSIONS: Greek patients prescribed teriparatide in ExFOS had severe osteoporosis with a high risk of fractures and back pain. Female patients shared similarities with EFOS counterparts, reflecting a constant prescribing profile for use of teriparatide, although a noticeable difference in fracture history between the two study cohorts may indicate a change towards prescribing in less severely affected patients. The economic crisis in Greece did not appear to affect patient enrolment. Data are interpreted in the context of an observational setting.

Association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty patients.

UNLABELLED: The objective of this study was to examine the association between teriparatide adherence and healthcare utilization and costs in real-world US kyphoplasty/vertebroplasty (KV) patients. Among KV patients newly initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs. INTRODUCTION: This study seeks to examine the association between teriparatide adherence and healthcare utilization/costs in real-world US KV patients. METHODS: Identified patients from a large US administrative claims database were aged 50+ with KV from 1/1/2002-12/31/2010 (first observed KV = index). Included individuals had 6+ months of pre-index continuous enrollment and no pre-index teriparatide, cancer, or Paget's disease. Follow-up period for patients initiating teriparatide was ≤36 months post-index. Three teriparatide adherence cohorts were constructed using the proportion of days covered (PDC) during the follow-up period: low (PDC ≤ 0.5), medium (PDC >0.5-≤ 0.8), and high (PDC >0.8). Repeated KV admissions, any inpatient admission, number of inpatient admissions, and per-patient-per-month (PPPM) inpatient, outpatient, pharmacy, and total costs were compared between cohorts. The associations between teriparatide adherence and healthcare utilization/costs were examined using multivariable regression models, adjusting for patient demographics and clinical characteristics. RESULTS: Included were 1,568 patients (mean age, 75 years; 82% female): 403 (26%) had low adherence, 382 (24%) medium, and 783 (50%) high. After multivariable adjustment, high adherence was significantly associated with the lowest PPPM inpatient (low = $1,287; medium = $1,005; high = $678) and outpatient (low = $1,464; medium = $1,244; high = $1,077) medical costs, but with increased pharmacy costs (low = $752; medium = $1,159; high = $1,616; all P < 0.05), leading to similar total costs (low = $3,344; medium = $3,376; high = $3,351) between cohorts; high adherence was also significantly associated with the lowest odds of repeated KV admission, any inpatient admission, and number of inpatient admissions (all P < 0.05). CONCLUSIONS: Among KV patients initiating teriparatide, significantly increased pharmacy costs associated with high teriparatide adherence were offset by significantly lower inpatient utilization and medical costs.

Association of teriparatide adherence and persistence with clinical and economic outcomes in Medicare Part D recipients: a retrospective cohort study.

BACKGROUND: Improper medication adherence is associated with increased morbidity, healthcare costs, and fracture risk among patients with osteoporosis. The objective of this study was to evaluate the healthcare utilization patterns of Medicare Part D beneficiaries newly initiating teriparatide, and to assess the association of medication adherence and persistence with bone fracture. METHODS: This retrospective cohort study assessed medical and pharmacy claims of 761 Medicare members initiating teriparatide in 2008 and 2009. Baseline characteristics, healthcare use, and healthcare costs 12 and 24 months after teriparatide initiation, were summarized. Adherence, measured by Proportion of Days Covered (PDC), was categorized as high (PDC ≥ 80%), moderate (50% ≥ PDC < 80%), and low (PDC < 50%). Non-persistence was measured as refill gaps in subsequent claims longer than 60 days plus the days of supply from the previous claim. Multivariate logistic regression evaluated the association of adherence and persistence with fracture rates at 12 months. RESULTS: Within 12 months of teriparatide initiation, 21% of the cohort was highly-adherent. Low-adherent or non-persistent patients visited the ER more frequently than did their highly-adherent or persistent counterparts (χ2 = 5.01, p < 0.05 and χ2 = 5.84, p < 0.05), and had significantly lower mean pharmacy costs ($4,361 versus $13,472 and $4,757 versus $13,187, p < 0.0001). Furthermore, non-persistent patients had significantly lower total healthcare costs. The healthcare costs of highly-adherent patients were largely pharmacy-related. Similar patterns were observed in the 222 patients who had fractures at 12 months, among whom 89% of fracture-related costs were pharmacy-related. The regression models demonstrated no significant association of adherence or persistence with 12-month fractures. Six months before initiating teriparatide, 50.7% of the cohort had experienced at least 1 fracture episode. At 12 months, these patients were nearly 3 times more likely to have a fracture (OR = 2.9, 95% C.I. 2.1-4.1 p < 0.0001). CONCLUSIONS: Adherence to teriparatide therapy was suboptimal. Increased pharmacy costs seemed to drive greater costs among highly-adherent patients, whereas lower adherence correlated to greater ER utilization but not to greater costs. Having a fracture in the 6 months before teriparatide initiation increased fracture risk at follow-up.

The cost effectiveness of teriparatide as a first-line treatment for glucocorticoid-induced and postmenopausal osteoporosis patients in Sweden.

BACKGROUND: This paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts. METHODS: A computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5. RESULTS: The ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively. CONCLUSIONS: The selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

Adherence and persistence with teriparatide among patients with commercial, Medicare, and Medicaid insurance.

UNLABELLED: Adherence to, and persistence with, treatments for osteoporosis are low. Adherence with teriparatide decreases over time. Higher copayments in the commercial/Medicare population were associated with worse persistence. Understanding factors such as prior screening, prior treatment history, and out of pocket costs that influence persistence with teriparatide may help clinicians make informed decisions. INTRODUCTION: The purpose of this study was to evaluate adherence and persistence with teriparatide. METHODS: Beneficiaries with at least one claim for teriparatide in 2003 or 2004 and continuous enrollment in the previous 12 months and subsequent 6 months were identified in a national commercial/Medicare and Medicaid administrative claims database (MarketScan®). Adherence was assessed through calculation of the medication possession ratio (MPR). Persistence was measured by time until discontinuation and time until first 60-day gap in treatment. Factors associated with persistence were assessed using Cox proportional hazards models. RESULTS: The average MPR at 6 months was 0.74 (N=2,218) and at 12 months, was 0.66 (N=1,303). At 6 months, 64.6% of patients remained on therapy and at 12 months, 56.7% remained. Bone mineral density screening and use of antiresorptive therapy within the 12 months pre-period, and lower patient copayments were associated with increased persistence. CONCLUSION: Patients appear to have good adherence with teriparatide over the first 6 months which declines over time. Prior screening and treatment of osteoporosis and out of pocket costs appear to impact persistence. To optimize patient outcomes, clinicians should consider clinical factors that impact persistence, while healthcare decision makers should consider the negative effect of higher patient copayments on persistence.

Teriparatide: a review of its use in osteoporosis.

Recombinant teriparatide (Forteo; Forsteo) is an anabolic (bone forming) agent. Studies have shown that subcutaneous teriparatide 20 microg/day is effective in women with postmenopausal osteoporosis, men with idiopathic or hypogonadal osteoporosis and patients with glucocorticoid-induced osteoporosis. Teriparatide improves bone mineral density (BMD) and alters the levels of bone formation and resorption markers; histomorphometric studies showed teriparatide-induced effects on bone structure, strength and quality. Subcutaneous teriparatide 20 microg/day administered over a treatment period of 11-21 months was effective in reducing the risk of fractures in and in improving BMD in men with idiopathic or hypogonadal osteoporosis, women with postmenopausal osteoporosis and patients with glucocorticoid-induced osteoporosis. Furthermore, the beneficial effects of teriparatide on vertebral fracture prevention and BMD appear to persist following treatment cessation. Teriparatide is generally well tolerated and treatment compliance rates are favourable. However, current limitations on the length of treatment and the high acquisition cost mean that teriparatide is best reserved for the treatment of patients with osteoporosis at high risk of fracture, or for patients with osteoporosis who have unsatisfactory responses to or intolerance of other osteoporosis therapies.

The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis.

BACKGROUND: Teriparatide is a promising new agent for the treatment of osteoporosis. METHODS: The objective of this study was to evaluate the cost-effectiveness of teriparatide-based strategies compared with alendronate sodium for the first-line treatment of high-risk osteoporotic women. We developed a microsimulation with a societal perspective. Key data sources include the Study of Osteoporotic Fractures, the Fracture Intervention Trial, and the Fracture Prevention Trial. We evaluated postmenopausal white women with low bone density and prevalent vertebral fracture. The interventions were usual care (UC) (calcium or vitamin D supplementation) compared with 3 strategies: 5 years of alendronate therapy, 2 years of teriparatide therapy, and 2 years of teriparatide therapy followed by 5 years of alendronate therapy (sequential teriparatide/alendronate). The main outcome measure was cost per quality-adjusted life-year (QALY). RESULTS: For the base-case analysis, the cost of alendronate treatment was 11,600 dollars per QALY compared with UC. The cost of sequential teriparatide/alendronate therapy was 156,500 dollars per QALY compared with alendronate. Teriparatide treatment alone was more expensive and produced a smaller increase in QALYs than alendronate. For sensitivity analysis, teriparatide alone was less cost-effective than alendronate even if its efficacy lasted 15 years after treatment cessation. Sequential teriparatide/alendronate therapy was less cost-effective than alendronate even if fractures were eliminated during the alendronate phase, although its cost-effectiveness was less than 50,000 dollars per QALY if the price of teriparatide decreased 60%, if used in elderly women with T scores of -4.0 or less, or if 6 months of teriparatide therapy had comparable efficacy to 2 years of treatment. CONCLUSIONS: Alendronate compares favorably to interventions accepted as cost-effective. Therapy with teriparatide alone is more expensive and produces a smaller increase in QALYs than therapy with alendronate. Sequential teriparatide/alendronate therapy appear expensive but could become more cost-effective with reductions in teriparatide price, with restriction to use in exceptionally high-risk women, or if short courses of treatment have comparable efficacy to that observed in clinical trials.

A Model for Assessing the Clinical and Economic Benefits of Bone-forming Agents for Reducing Fractures in Postmenopausal Women at High, Near-term Risk of Osteoporotic Fracture.

PURPOSE: The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime horizon with sequenced antiresorptive agents for maintenance treatment. METHODS: Analyses were performed by using a Markov cohort model accounting for time-specific fracture protection effects of bone-forming agents followed by antiresorptive treatment with denosumab. The alternative bone-forming agent profiles were defined by using assumptions regarding the onset and total magnitude of protection against fractures with teriparatide. The model cohort comprised 70-year-old female patients with T scores below -2.5 and a previous vertebral fracture. Outcomes included clinical fractures, direct costs, and quality-adjusted life years. The simulated treatment strategies were compared by calculating their incremental "value" (net monetary benefit). FINDINGS: Improvements in the onset and magnitude of fracture protection (vs the teriparatide reference case) produced a net monetary benefit of $17,000,000 per 10,000 treated patients during the (1.5-year) bone-forming agent treatment period and $80,000,000 over a lifetime horizon that included 3.5 years of maintenance treatment with denosumab. IMPLICATIONS: Incorporating time-specific fracture effects in the Markov cohort model allowed for estimation of a range of cost savings, quality-adjusted life years gained, and clinical fractures avoided at different levels of fracture protection onset and magnitude. Results provide a first estimate of the potential "value" new bone-forming agents (romosozumab and abaloparatide) may confer relative to teriparatide.

Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy.

OBJECTIVE: The objective was to evaluate compliance with osteoporosis (OP) treatments and determine the fracture and healthcare burden associated with noncompliance. METHODS: This retrospective analysis of a US claims database identified women initiating an OP medication from 1 January 2002 to 30 June 2009. Patients were ≥55 years and had ≥1 pharmacy claim for a bisphosphonate or non-bisphosphonate (raloxifene, calcitonin, teriparatide); the index date was the first pharmacy claim. There were three study periods: baseline (12 months pre-index); compliance period (0-12 months post-index); and follow-up period (12-24 months post-index). Medication possession ratio (MPR) was calculated during the compliance period to differentiate two cohorts: compliant (MPR ≥ 80%) and noncompliant (MPR < 80%). Outcomes during follow-up were modeled by logistic regression (presence of fracture), Poisson regression (healthcare utilization incidence rate) and gamma regression (healthcare costs), all adjusted for patient demographic and clinical characteristics. RESULTS: Overall, 685,505 women initiating OP therapy were identified and 57,913 (8.4%) met the inclusion criteria: only 23,430 (40.5%) were compliant and 34,483 (59.5%) were noncompliant. Mean age was 64 years. Noncompliance was associated with a 20% higher risk of any fracture (odds ratio: 1.20, 95% CI = 1.07-1.35), a higher incidence rate ratio (IRR) for inpatient utilization (IRR: 1.26, 95% CI = 1.19-1.34) and a lower rate of outpatient utilization (IRR: 0.97, 95% CI = 0.95-0.98). Noncompliant patients had 13% higher medical costs (cost ratio: 1.13, 95% CI = 1.06-1.21) than compliant patients. LIMITATIONS: Inclusion in this study required 36 months of continuous healthcare coverage. Thus, the results are primarily applicable to a stable, managed care population and may not be generalizable to other populations. CONCLUSION: Noncompliance with OP therapy was associated with a higher risk of fracture, higher all-cause medical costs and a higher frequency of inpatient service utilization. Additional research is needed to identify barriers to compliance with OP therapy.

Comparing clinical and economic outcomes of biologic and conventional medications in postmenopausal women with osteoporosis.

RATIONALE, AIMS AND OBJECTIVES: Biologics are substantially more expensive than their conventional counterparts but it is unclear whether extra costs deliver better health outcomes. We compare clinical and economic outcomes between teriparatide (monthly costs $1120) and bisphosphonates (monthly costs $14) among postmenopausal women with osteoporosis. METHODS: From a 5% random sample of Medicare beneficiaries, we selected women newly diagnosed with osteoporosis between 1 January 2007 and 31 December 2011 and who initiated teriparatide or bisphosphonates after the diagnosis. We followed them up until one of these events: switching osteoporosis treatment, death, or the end of study period - 31 December 2011. Clinical outcomes included hip fracture, vertebral fracture, fracture of radius, ulna or carpal bones, other upper limb fractures, other lower limb fractures and any fracture. Economic outcomes included medical costs, pharmacy costs, and total costs associated with osteoporosis. Using conventional propensity score, high-dimensional propensity score and instrumental variable analysis, we constructed Cox proportional hazards models to evaluate the risk of fracture and two-part models to compare costs. RESULTS: Teriparatide users had higher risk of fracture and higher costs, compared with similar bisphosphonates users. The hazard ratios of fracture for teriparatide relative to bisphosphonates ranged from 1.37 to 2.12, depending on methods. There was no difference in the risk of hip fracture between treatment groups. Total annual costs related to osteoporosis were between $2733 and $3352 higher for teriparatide users. CONCLUSIONS: The biological agent, teriparatide, is more expensive yet less effective than conventional treatment, bisphosphonates.

Teriparatide: a review.

BACKGROUND: Traditionally, the management of osteoporosis in men and women has included the use of antiresorptive agents in combination with calcium and vitamin D supplementation. The mechanism of action of teriparatide is unique in that it possesses anabolic properties and therefore builds bone. Since the approval of teriparatide in the United States in 2002, a great deal of interest regarding its use in osteoporosis has developed. OBJECTIVES: This article reviews the information available on the new recombinant human parathyroid hormone teriparatide (hPTH [1-34]), including its clinical pharmacology, mechanism of action, pharmacokinetic properties, clinical efficacy, safety profile, potential drug interactions, contraindications and warnings, dosage and administration, and pharmacoeconomics. METHODS: The articles included in this review were identified through searches of PubMed and MEDLINE (1966-December 2003) and International Pharmaceutical Abstracts (1970-December 2003). Search terms included teriparatide, Forteo, recombinant human parathyroid hormone (1-34), and osteoporosis. The references of the identified articles were reviewed for additional publications. Specific product information was also obtained from the manufacturer of teriparatide. RESULTS: Teriparatide has been studied in postmenopausal women with osteoporosis, drug-induced osteoporosis (specifically, corticosteroid-induced osteoporosis), and men with osteoporosis. The data available from various clinical trials have shown an increase in both bone mineral density (BMD) and bone mineral content (BMC) with the use of teriparatide compared with placebo. One study found that women treated with the 20-microg dose and the 40-microg dose were 35% and 40%, respectively, less likely to have one or more new nonvertebral fractures compared with placebo (P = 0.02). Another study compared the use of daily teriparatide 40-microg injections versus oral daily alendronate. Results showed that the incidence of nonvertebral fractures was significantly lower in the teriparatide group than the alendronate group (P < 0.05). A study using 20- and 40-microg daily injections of teriparatide was performed in men with osteoporosis. There was a statistically significant increase in lumbar spine BMD of 5.9% in the 20-microg group and 9.0% in the 40-microg group (both, P < 0.001). In the femoral neck, a 1.5% increase in BMD occurred in the 20-microg group (P = 0.021) and a 0.9% increase in the 40-microg group (P < 0.001). A limited number of studies are available assessing the combination of antiresorptive medications and teriparatide; however, the available data suggest that the effects of teriperatide do not require prior stimulation of bone resorption. CONCLUSIONS: Teriparatide has been shown clinically to improve BMD and BMC in postmenopausal women and in men. Because of its anabolic capabilities, teriparatide can be used as an alternative to the traditional therapies that are currently available for the treatment of osteoporosis, with scheduled monitoring for adverse effects such as hypercalcemia and urinary calcium excretion. In 1 study, mild hypercalcemia was seen most often 4 to 6 hours after SC injection of teriparatide before returning to normal. Urinary calcium was observed to increase by 30 mg/d (0.75 mmol/d) with teriparatide.

Recombinant human PTH 1-34 (Forteo): an anabolic drug for osteoporosis.

Forteo (teriparatide of rDNA origin), a genetically engineered fragment of parathyroid hormone, is the first of a new class of drugs to treat osteoporosis. The drug's anabolic action increases bone turnover, stimulating osteoblasts to a greater extent than osteoclasts, and reducing both vertebral and nonvertebral fractures. However, a number of issues about its use remain unanswered.

Association between teriparatide adherence and healthcare utilization and costs among hip fracture patients in the United States.

PURPOSE: This study examined the association between teriparatide (TPTD) adherence, and healthcare utilization and costs among hip fracture (HFx) patients. METHODS: Individuals aged 50years and older with an HFx between 1/1/2002-12/31/2010 were identified from a large US administrative claims database. The first HFx date during this period was designated as the index. Selected patients had at least 6months of pre-index continuous enrollment (baseline) and no baseline TPTD use, cancer, or Paget's disease. Patients initiating TPTD post-index were followed until censoring at switch to bisphosphonates, disenrollment, 36months post-index, or diagnosis of cancer or Paget's disease. Teriparatide adherence was measured as the proportion of days covered (PDC) by TPTD prescriptions, during the follow-up period, to construct three adherence groups: low (PDC≤0.5), medium (0.50.8) adherence. Outcome measures were repeated HFx, number of inpatient admissions, and per-patient-per-month (PPPM) healthcare costs. Multivariable generalized linear models examined the association between the TPTD adherence groups and the outcomes, adjusting for cross-group differences in patient characteristics. RESULTS: A total of 824 patients (mean age 75years, 90% female) were included: 30% low, 27% medium, and 44% high adherence. In multivariable analyses, high adherence was significantly (all p<0.05) directly associated with increased PPPM pharmacy costs ($621 low, $1093 medium, and $1572 high), but also with the lowest inpatient ($963 low, $960 medium, and $629 high) and outpatient ($1087 low, $1068 medium, and $776 high) costs, leading to the highest total costs in the medium adherence group but similar costs in the high and low adherence groups ($2599 low, $3163 medium, and $2869 high). The high adherence group also had the lowest number of inpatient admissions. CONCLUSIONS: Significantly increased pharmacy costs associated with the high TPTD adherence group were offset by significantly fewer inpatient admissions, fewer repeated HFx, and lower inpatient and outpatient costs.

Using common random numbers in health care cost-effectiveness simulation modeling.

OBJECTIVES: To identify the problem of separating statistical noise from treatment effects in health outcomes modeling and analysis. To demonstrate the implementation of one technique, common random numbers (CRNs), and to illustrate the value of CRNs to assess costs and outcomes under uncertainty. METHODS: A microsimulation model was designed to evaluate osteoporosis treatment, estimating cost and utility measures for patient cohorts at high risk of osteoporosis-related fractures. Incremental cost-effectiveness ratios (ICERs) were estimated using a full implementation of CRNs, a partial implementation of CRNs, and no CRNs. A modification to traditional probabilistic sensitivity analysis (PSA) was used to determine how variance reduction can impact a decision maker's view of treatment efficacy and costs. RESULTS: The full use of CRNs provided a 93.6 percent reduction in variance compared to simulations not using the technique. The use of partial CRNs provided a 5.6 percent reduction. The PSA results using full CRNs demonstrated a substantially tighter range of cost-benefit outcomes for teriparatide usage than the cost-benefits generated without the technique. CONCLUSIONS: CRNs provide substantial variance reduction for cost-effectiveness studies. By reducing variability not associated with the treatment being evaluated, CRNs provide a better understanding of treatment effects and risks.