Cost-effectiveness of denosumab for high-risk postmenopausal women with osteoporosis in Thailand.

Aims: This study assessed the cost-effectiveness of denosumab for treating postmenopausal women with osteoporosis (PMO) at high risk of fracture in Thailand.Materials and methods: A published Markov cohort cost-effectiveness model was populated with country-specific data as available and other published data as needed. The model used a societal perspective, lifetime horizon, efficacy data from network meta-analysis of trials, and included costs for direct medical and non-medical care, informal care, and osteoporosis treatments to compare denosumab to no pharmacologic treatment (calcium and vitamin D supplements only) and to oral weekly alendronate. The base case (high-risk population) included postmenopausal women with femoral neck T-score ≤-2.5, mean age 65 years at entry, and history of vertebral fracture.Results: High-risk women with osteoporosis using denosumab had the greatest number of life years and quality-adjusted life-years (QALYs) with higher reductions in hip and vertebral fracture incidence compared with patients with no pharmacologic treatment. The incremental cost-effectiveness ratio (ICER) was 119,575 Thai Baht (THB) per QALY for denosumab versus no pharmacologic treatment and 199,186 THB per QALY for denosumab versus alendronate. Among Thai postmenopausal women with high-risk of fractures, denosumab was cost-effective compared with no pharmacologic treatment at a willingness-to-pay threshold of 160,000 THB per QALY. One-way sensitivity analysis showed models were most sensitive to changes in denosumab pricing.Limitations: Data from other countries used when country-specific data were unavailable may not accurately reflect the true experience in Thailand. The model focused explicitly on hip, vertebral, and wrist fractures, and therefore provides a conservative estimate of the overall potential impact of osteoporosis-related fracture. The fracture risk was not adjusted to reflect potential changes in risk after denosumab treatment discontinuation.Conclusions: In Thailand, denosumab offers a cost-effective osteoporosis treatment option versus no pharmacologic treatment in postmenopausal women at high risk of fracture.

Patient-Level Modeling Approach Using Discrete-Event Simulation: A Cost-Effectiveness Study of Current Treatment Guidelines for Women with Postmenopausal Osteoporosis.

Decision tree and Markov models have been the most commonly used modeling methods in health economic evaluations. Both methods are known for their limitations. Discrete-event simulation (DES), an event-driven model in continuous time at the patient level, is a relatively new method in health economic evaluations that addresses some limitations of the common modeling techniques. Specifically, with the advent of personalized medicine, conventional methods for value assessment that are based on population-level measures might not be appropriate. The best treatment would depend on patient characteristics and clinical profiles. Value assessment of health interventions can vary substantially and may lead to different health decision making due to patient heterogeneity. As such, modeling at the patient level is an appropriate approach for value assessment of health interventions. The DES model has several advantages, such as flexibility, ability to reflect patient heterogeneity, increased precision, and better characterization of modeling uncertainty, that may be preferred to decision tree and Markov models. In addition, with increasing health care spending and drug prices, it is important to quantify value of available treatment options for women with postmenopausal osteoporosis (PMO). The purpose of this Viewpoints article was to describe and demonstrate an application of a DES model to evaluate the cost-effectiveness of the current treatment guidelines for women with PMO. In particular, the DES model indicated that the optimal treatment at the common willingness-to-pay thresholds between $100,000 per quality-adjusted life-year (QALY) and $150,000 per QALY was denosumab. Analysis of patient heterogeneity in terms of low, medium, high, and very high risk of fractures resulted in a similar conclusion. DISCLOSURES: Funding for this study was received through the PhRMA Foundation Value Assessment Challenge Award. The author has no conflicts of interest to declare.

Cost-effectiveness of pharmacological fracture prevention for osteoporosis as prescribed in clinical practice in France, Germany, Italy, Spain, and the United Kingdom.

This study estimated the cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries (EU5) using the IOF reference cost-effectiveness model. Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each of the EU5. PURPOSE: To estimate the real-world cost-effectiveness of pharmacological fracture prevention as prescribed in the five largest European countries by population size: France, Germany, Italy, Spain, and the United Kingdom (UK) (collectively EU5). MATERIALS AND METHODS: We analyzed sales data on osteoporosis drugs in each of the EU5 to derive a hypothetical intervention that corresponds to the mix of osteoporosis medication prescribed in clinical practice. The costs for this treatment mix were obtained directly from the sales data, and the efficacy of the treatment mix was estimated by weighing the treatment-specific fracture risk reductions from a published meta-analysis. Subsequently, we estimated the cost-effectiveness using costs per quality adjusted life year (QALY) of the intervention compared to no treatment in each of the EU5 using the International Osteoporosis Foundation (IOF) reference cost-effectiveness model. The model population comprised postmenopausal women, mean age 72 years with established osteoporosis (T-score ≤ - 2.5) among whom 23.6% had a prevalent vertebral fracture. The model was populated with country-specific data from the literature. RESULTS: Pharmacological fracture prevention as prescribed in clinical practice was cost-saving (provided more QALYs at lower costs) compared to no treatment in each country. The findings were robust in scenario analyses. CONCLUSIONS: Pharmacological fracture prevention as prescribed in clinical practice is cost-saving in each of the EU5. Because of the under-diagnosis and under-treatment of post-menopausal osteoporosis, from a health economic perspective, further cost-savings may be reached by expanding treatment to those at increased risk of fracture currently not receiving any treatment.

Cost-effectiveness of antiosteoporosis strategies for postmenopausal women with osteoporosis in China.

OBJECTIVE: Osteoporosis has become an important public health problem in China, especially among elderly postmenopausal women. Massive amounts of medical and health resources have been devoted to patients with osteoporosis and osteoporosis-related fractures. This study estimated the cost-effectiveness of alendronate, zoledronate, raloxifene, teriparatide, and calcium/vitamin D as treatments for osteoporosis in elderly postmenopausal women in China from the medical system perspective. METHODS: A Markov model was constructed by using TreeAge Pro 2015 software. This model simulated the disease process over 40 years in response to the five investigated therapeutic strategies. Each cycle lasted for 1 year. The model parameters included Chinese epidemiological data, clinical effectiveness, cost, and utility. Total treatment costs and quality-adjusted life-years (QALYs) were estimated, and incremental cost-effectiveness analysis was performed. Univariate and probabilistic sensitivity analyses were conducted to verify the model. RESULTS: The calcium/vitamin D strategy, zoledronate, alendronate, teriparatide, and raloxifene offered patients 10.24, 10.83, 10.70, 10.88, and 10.54 QALYs at the cost of $3,799.72, $8,425.61, $9,849.89, $34,843.72, and $13,353.33 for over 40 years, respectively. The alendronate and raloxifene strategies were eliminated because they were less effective and more expensive than the other strategies. The base-case analysis revealed that the incremental cost-effectiveness ratios (ICERs) of the zoledronate strategy relative to those of the calcium/vitamin D strategy were $7,864.59/QALY. This result indicated that the zoledronate strategy was more cost-effective than other strategies and was within the willingness-to-pay threshold of China ($28,624/QALY). The ICERs of the teriparatide versus zoledronate strategies were $4,70,797.08/QALY, which exceeded the threshold. CONCLUSION: From the perspective of the Chinese medical system, zoledronate is more cost-effective than the calcium/vitamin D strategy, alendronate, raloxifene, and teriparatide for the treatment of osteoporosis in elderly postmenopausal women. Not factoring the parameters of adherence and persistence in, and consequent variability in treatment effectiveness relative risks, seems like a major limitation, but it can be speculated that it would not change the conclusion that zoledronate is the most economical strategy.

Cost-effectiveness of gastro-resistant risedronate tablets for the treatment of postmenopausal women with osteoporosis in France.

The use of gastro-resistant risedronate, a convenient dosing regimen for oral bisphosphonate therapy, seems a cost-effective strategy compared with weekly alendronate, generic risedronate, and no treatment for the treatment of postmenopausal women with osteoporosis in France. INTRODUCTION: Gastro-resistant (GR) risedronate tablets are associated with improved persistence compared to common oral bisphosphonates but are slightly more expensive. This study assessed its cost-effectiveness compared to weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France. METHODS: A previously validated Markov microsimulation model was used to estimate the lifetime costs (expressed in €2017) per quality-adjusted life-years (QALY) of GR risedronate compared with weekly alendronate, generic risedronate, and no treatment. Pooled efficacy data for bisphosphonates derived from a previous meta-analysis were used for all treatment options, and persistence data (up to 3 years) were obtained from a large Australian longitudinal study. Evaluation was done for high-risk women 60-80 years of age, with a bone mineral density (BMD) T-score ≤ - 2.5 and/or prevalent vertebral fractures. RESULTS: In all of the simulated populations, GR risedronate was cost-effective compared to alendronate, generic risedronate, and no treatment at a threshold of €60,000 per QALY gained. In women with a BMD T-score ≤ - 2.5 and prevalent vertebral fractures, the cost per QALY gained of GR risedronate compared to alendronate, generic risedronate, and no treatment falls below €20,000 per QALY gained. In women aged 75 years and older, GR risedronate was even shown to be dominant (more QALYs, less costs) compared to alendronate, generic risedronate, and no treatment. CONCLUSION: This study provides the first economic results about GR risedronate, suggesting that it represents a cost-effective strategy compared with weekly alendronate and generic risedronate for the treatment of postmenopausal women with osteoporosis in France.

Executive summary of the European guidance for the diagnosis and management of osteoporosis in postmenopausal women.

A guidance on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis was recently published in Osteoporosis International as a joint effort of the International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (Kanis et al. in Osteoporos Int https://doi.org/10.1007/s00198-018-4704-5 , 2018). This manuscript updates the previous guidelines document, published in 2013 (Kanis et al. in Osteoporos Int 24:23-57, 2013) and is written in a European perspective. The present article reports and summarizes the main recommendations included in this 2018 guidance document.

Cost-effectiveness of implementing guidelines for the treatment of glucocorticoid-induced osteoporosis in Japan.

A model-based cost-effectiveness analysis was performed to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO). The treatment indication for GIO in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture. INTRODUCTION: The purpose of this study was to evaluate the cost-effectiveness of implementing the clinical guideline for the treatment for glucocorticoid-induced osteoporosis (GIO) from the perspective of the Japanese healthcare system. METHODS: A patient-level state transition model was developed to predict lifetime costs and quality-adjusted life years (QALYs) in postmenopausal Japanese women with osteopenia or osteoporosis using glucocorticoid (GC). An annual discount rate of 2% for both costs and QALYs was applied. The incremental cost-effectiveness ratio (ICER) of 5-year alendronate therapy compared with no therapy was estimated with different combinations of the risk factors such as starting age (45, 55, or 65), femoral neck BMD (% young adult mean (YAM) of 70%, 75%, or 80%), dose of GC (2.5, 5, or 10 mg per day), and the presence of previous fracture (yes or no). RESULTS: For 55-year-old women using GC with a BMD of 75% of YAM, the ICER ranged from $10,958 to $ 29,727 per QALY. Scenario analyses indicated that the lower age, the lower BMD, the higher dose of GC, and the presence of previous fracture associated with lower ICER. The best-case scenario was 45-year-old women with a BMD of 70% of YAM, GC dose of 10 mg per day, and previous fracture, and resulted in healthcare cost-savings. The worst-case scenario was 65-year-old women with a BMD of 80% of YAM, GC dose of 2.5 mg per day, and no previous fracture, and resulted in the ICER of $66,791 per QALY. Sensitivity analyses in the worst-case scenario showed that the annual discount rate for costs and health benefit had the strong influence on the estimated ICER. Although the ICER was influenced by other parameters such as disutility due to vertebral fracture, efficacy of alendronate, and so on, the ICERs remained more than $50,000 per QALY. CONCLUSIONS: The cost-effectiveness of preventive alendronate therapy for postmenopausal women with osteopenia or osteoporosis using GC is sensitive to age, BMD, GC dose, and the presence of previous fracture. Our analysis suggested that the treatment indication for postmenopausal women with osteopenia or osteoporosis using GC in the current Japanese clinical guidelines is likely to be cost-effective except for the limited patients who are at low risk for fracture.

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.

Cost-effectiveness analysis of drugs for osteoporosis treatment in elderly Japanese women at high risk of fragility fractures: comparison of denosumab and weekly alendronate.

This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment. Denosumab treatment was cost-effective compared with alendronate treatment for elderly Japanese women at high risk of fragility fractures. Denosumab treatment might be cost-effective for patients with lower bone mineral density. PURPOSE: In Japan's super-aged society, the prevention and treatment of osteoporosis are a critical issue with implications for the medical economy. This study's purpose was to clarify the cost-effectiveness of osteoporosis treatment with denosumab versus weekly alendronate for elderly Japanese women at high risk of fragility fractures. METHODS: A Markov model was used for simulation analysis. The modeled population was 75-year-old Japanese women with a bone mineral density (BMD) of 65% of the young adult mean (YAM) (T-score, - 2.87) and a history of previous vertebral body fracture. The simulation model was repeated until patient age reached 100 years or death. Analysis was performed from the societal perspective. Costs and epidemiological data were derived from previous studies. The incremental cost-effectiveness ratio (ICER) was calculated from the simulation. We compared the ICER with willingness-to-pay. Additional analyses were performed with different combinations of age and BMD. Sensitivity analysis verified the robustness of the analysis. RESULTS: For the modeled population, the ICER of denosumab versus alendronate treatment was estimated at US$40,241/quality-adjusted life year (QALY). The ICER of denosumab for 80-year-old women whose BMD was 60% of YAM was estimated at US$22,469/QALY. CONCLUSIONS: Assuming willingness-to-pay as US$50,000/QALY, denosumab treatment for 75-year-old Japanese women with a BMD of 65% of YAM and a history of previous vertebral body fracture was cost-effective compared with alendronate treatment. Among over 75 years of age, denosumab treatment might be more cost-effective than alendronate for patients with a BMD of 65% of YAM or lower.

Medication persistence and risk of fracture among female Medicare beneficiaries diagnosed with osteoporosis.

We examined the relationship between persistent osteoporosis medication use and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis using Medicare claims, 2009-2012. Persistent use was associated with reduced risk of fracture and significantly lower total health care costs in the follow-up period. Results were consistent using different analytical methods. INTRODUCTION: This study aimed to examine the relationship between medication persistence and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis. METHODS: Elderly female Medicare beneficiaries diagnosed with osteoporosis and initiated on osteoporosis medication January 1, 2009-June 30, 2011, were included. Persistent medication use was defined as continuous use (no gap ≥ 60 days) for 1 year or longer. The key outcome was fragility fracture. A difference-in-difference analysis was performed at the log scale of fracture rate using a Poisson regression model with months 1-6 before medication initiation as the pre-initiation period and up to 18 months after as the post-initiation period. Total health care costs were compared using a similar approach. Sensitivity analyses were conducted using different pre- and post-initiation periods. RESULTS: The study included 294,369 patients; 32.9% were persistent osteoporosis medication users and 67.1% non-persistent (< 12 months continuous use). Fracture incidence rates were 16.2 per 100 patient-years pre-initiation and 4.1 post-initiation for persistent users; corresponding rates for non-persistent users were 19.0 and 7.3 per 100 patient-years. The adjusted post-/pre-initiation fracture rate ratios were 0.284 for persistent and 0.411 for non-persistent users. The ratio of the two rate ratios was 0.692 (persistent vs. non-persistent, p < 0.0001), suggesting a significantly greater fracture rate reduction for persistent users. Adjusted cost ratios were significantly lower for persistent users. Sensitivity analyses results were similar. CONCLUSIONS: Persistent use of osteoporosis medications was associated with reduced risk of fracture and significantly lower total health care costs. Payers and patients would benefit from interventions aimed at improving medication persistence.

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-effectiveness of Virtual Bone Strength Testing in Osteoporosis Screening Programs for Postmenopausal Women in the United States.

Purpose To investigate whether assessment of bone strength with quantitative computed tomography (CT) in combination with dual-energy x-ray absorptiometry (DXA) is cost-effective as a screening tool for osteoporosis in postmenopausal women. Materials and Methods A state-transition microsimulation model of osteoporosis for postmenopausal women aged 55 years or older was developed with a lifetime horizon and U.S. societal perspective. All model inputs were derived from published literature. Three strategies were compared: no screening, DXA with T score-dependent rescreening intervals, and a combination of DXA and quantitative CT with different intervals (3, 5, and 10 years) at different screening initiation ages (55-65 years). Oral bisphosphonate therapy was started if DXA hip T scores were less than or equal to -2.5, 10-year risk for hip fracture was greater than 3% (World Health Organization Fracture Risk Assessment Tool score, or FRAX), 10-year risk for major osteoporotic fracture was greater than 20% (FRAX), quantitative CT femur bone strength was less than 3000 N, or occurrence of first fracture (eg, hip, vertebral body, wrist). Outcome measures were incremental cost-effectiveness ratios (ICERs) in 2015 U.S. dollars per quality-adjusted life year (QALY) gained and number of fragility fractures. Probabilistic sensitivity analysis was also performed. Results The most cost-effective strategy was combined DXA and quantitative CT screening starting at age 55 with quantitative CT screening every 5 years (ICER, $2000 per QALY). With this strategy, 12.8% of postmenopausal women sustained hip fractures in their remaining life (no screening, 18.7%; DXA screening, 15.8%). The corresponding percentages of vertebral fractures for DXA and quantitative CT with a 5-year interval, was 7.5%; no screening, 11.1%; DXA screening, 9%; for wrist fractures, 14%, 17.8%, and 16.4%, respectively; for other fractures, 22.6%, 30.8%, and 27.3%, respectively. In probabilistic sensitivity analysis, DXA and quantitative CT at age 55 years with quantitative CT screening every 5 years was the best strategy in more than 90% of all 1000 simulations (for thresholds of $50 000 per QALY and $100 000 per QALY). Conclusion Combined assessment of bone strength and bone mineral density is a cost-effective strategy for osteoporosis screening in postmenopausal women and has the potential to prevent a substantial number of fragility fractures. © RSNA, 2017 Online supplemental material is available for this article.

Treatment of postmenopausal osteoporosis: a literature-based algorithm for use in the public health care system.

Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

Treatment of postmenopausal osteoporosis: a literature-based algorithm for use in the public health care system / Tratamento da osteoporose pós-menopáusica: um algoritmo baseado na literatura para uso no sistema público de saúde

ABSTRACT Bisphosphonates are considered first-line agents in the treatment of postmenopausal osteoporosis based on extensive experience of use, safety, and proven efficacy in reducing vertebral, non-vertebral and femur fractures. However, post-marketing reports based on the treatment of millions of patients/year over lengthy periods of time have revealed the occurrence of initially unexpected adverse effects, such as osteonecrosis of the jaw and atypical femoral fracture, leading to the restriction of treatment duration with bisphosphonates by global regulatory agencies. However, despite the association between these effects and bisphosphonates, this risk should be analyzed in the context of osteoporosis treatment, alongside the benefit of preventing osteoporotic fractures and their clinical consequences. Therefore, we consider it plausible to discuss the restriction to the use of bisphosphonates, possible indications for prolonged treatment and alternative therapies following the suspension of this drug class for patients with persistent high risk of fracture after initial treatment, especially considering the problems of public health funding in Brazil and the shortage of drugs provided by the government. Thus, to standardize the treatment of osteoporosis in the public health care system, we aim to develop a proposal for a scientifically-based pharmacological treatment for postmenopausal osteoporosis, establishing criteria for indication and allowing the rational use of each pharmacological agent. We discuss the duration of the initial bisphosphonate treatment, the therapeutic options for refractory patients and potential indications of other classes of drugs as first-choice treatment in the sphere of public health, in which assessing risk and cost effectiveness is a priority.

RESUMO Com base na vasta experiência de uso, segurança e eficácia comprovada na redução de fraturas vertebrais, não vertebrais e femorais, os bisfosfonatos são considerados agentes de primeira linha no tratamento da osteoporose pós-menopáusica. No entanto, os relatos pós-venda baseados no tratamento de milhões de pacientes/ano durante períodos prolongados de tempo revelaram a ocorrência de efeitos adversos inicialmente inesperados, como osteonecrose da mandíbula e fratura atípica do fêmur. Isso levou as agências reguladoras globais a restringirem a duração do tratamento com bisfosfonatos. No entanto, apesar da associação entre esses efeitos e os bisfosfonatos, esse risco deve ser analisado no contexto do tratamento da osteoporose, paralelamente ao benefício na prevenção de fraturas osteoporóticas e suas consequências clínicas. Portanto, considera-se plausível discutir a restrição ao uso dos bisfosfonatos, possíveis indicações para o tratamento prolongado e terapias opcionais após a suspensão dessa classe de fármaco para pacientes com alto risco persistente de fratura após o tratamento inicial, especialmente se considerarmos os problemas financeiros de saúde pública no Brasil e a escassez de fármacos fornecidos pelo governo. Assim, para padronizar o tratamento da osteoporose no sistema público de saúde pretende-se desenvolver uma proposta de tratamento farmacológico cientificamente fundamentada para a osteoporose pós-menopáusica, estabelecer critérios de indicação e permitir o uso racional de cada agente farmacológico. Discutem-se a duração do tratamento inicial com bisfosfonatos, as opções terapêuticas para pacientes refratários e potenciais indicações de outras classes de medicamentos como tratamento de primeira linha na esfera da saúde pública, em que a avaliação do risco e custo-efetividade é uma prioridade.

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.

Cost-effectiveness analysis of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan.

Model-based economic evaluation was performed to assess the cost-effectiveness of zoledronic acid. Although zoledronic acid was dominated by alendronate, the incremental quality-adjusted life year (QALY) was quite small in extent. Considering the advantage of once-yearly injection of zoledronic acid in persistence, zoledronic acid might be a cost-effective treatment option compared to once-weekly oral alendronate. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan. METHODS: A patient-level state-transition model was developed to predict the outcome of patients with osteoporosis who have experienced a previous vertebral fracture. The efficacy of zoledronic acid was derived from a published network meta-analysis. Lifetime cost and QALYs were estimated for patients who had received zoledronic acid, alendronate, or basic treatment alone. The incremental cost-effectiveness ratio (ICER) of zoledronic acid was estimated. RESULTS: For patients 70 years of age, zoledronic acid was dominated by alendronate with incremental QALY of -0.004 to -0.000 and incremental cost of 430 USD to 493 USD. Deterministic sensitivity analysis indicated that the relative risk of hip fracture and drug cost strongly affected the cost-effectiveness of zoledronic acid compared to alendronate. Scenario analysis considering treatment persistence showed that the ICER of zoledronic acid compared to alendronate was estimated to be 47,435 USD, 27,018 USD, and 10,749 USD per QALY gained for patients with a T-score of -2.0, -2.5, or -3.0, respectively. CONCLUSION: Although zoledronic acid is dominated by alendronate, the incremental QALY is quite small in extent. Considering the advantage of annual zoledronic acid treatment in compliance and persistence, zoledronic acid may be a cost-effective treatment option compared to alendronate.

Cost-effectiveness of denosumab versus oral alendronate for elderly osteoporotic women in Japan.

We constructed a Markov microsimulation model among hypothetical cohorts of community-dwelling elderly osteoporotic Japanese women without prior hip or vertebral fractures over a lifetime horizon. Compared with weekly oral alendronate for 5 years, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold. INTRODUCTION: The objective of the study was to examine the cost-effectiveness of subcutaneous denosumab every 6 months for 5 years compared with weekly oral alendronate for 5 years in Japan. METHODS: We calculated incremental cost-effectiveness ratios [ICERs] (2016 US dollars [$] per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling osteoporotic Japanese women without prior hip or vertebral fractures at various ages of therapy initiation (65, 70, 75, and 80 years) over a lifetime horizon from three perspectives: societal, healthcare sector, and government. RESULTS: Denosumab was cost-saving compared with alendronate at ages 75 and 80 years from any of the three perspectives. The ICERs of denosumab compared with alendronate were $25,700 and $5000 per QALY at ages 65 and 70 years from a societal perspective and did not exceed a willingness-to-pay of $50,000 per QALY from the other two perspectives. In deterministic sensitivity analyses, results were sensitive to changes in the effectiveness of denosumab for reducing hip fracture and clinical vertebral fracture and the rate ratio of non-persistence with denosumab compared to alendronate. In probabilistic sensitivity analyses, the probabilities of denosumab being cost-effective compared with alendronate were 89-100% at a willingness-to-pay of $50,000 per QALY. CONCLUSIONS: Among community-dwelling elderly osteoporotic women in Japan, denosumab every 6 months for 5 years is cost-saving or cost-effective at a conventionally accepted threshold of willingness-to-pay at all ages examined, compared with weekly alendronate for 5 years. This study provides insight to clinicians and policymakers regarding the relative economic value of osteoporosis treatments in elderly women.

Cost-effectiveness of dual-energy X-ray absorptiometry plus antiresorptive treatment in Australian women with breast cancer who receive aromatase inhibitors.

Postmenopausal women with breast cancer on aromatase inhibitor (AI) treatment are at increased risk of bone mineral density loss, which may lead to minimal trauma fractures. We examined the cost-effectiveness of dual energy X-ray absorptiometry (DXA) with antiresorptive (AR) therapy compared with fracture risk assessment, lifestyle advice, and vitamin supplementation. We used a hypothetical Markov cohort model of lifetime duration for 60-year-old women with early stage breast cancer receiving AIs. The data to inform the model came from medical literature, epidemiological reports, and costing data sets. Two eligibility scenarios for AR therapy were considered: (A) osteoporosis and (B) osteopenia or osteoporosis. The main outcomes were incremental cost per quality-adjusted life years gained and cumulative fractures per 1000 women, calculated relative to the comparator. Key aspects of the model were explored in sensitivity analyses. Due to relatively low effectiveness gains, the outcomes were primarily driven by the costs. The incremental cost per quality-adjusted life year gained was A$47,556 and A$253,000 for scenarios A and B, respectively. The numbers of fractures avoided were 56 and 77 per 1000 women, respectively. The results were most sensitive to the initial probability of osteoporosis, baseline risk of fracture, and cohort starting age. Compared with risk assessment and lifestyle advice only, a DXA scan followed by an AR treatment is potentially cost-effective for women aged 60 and over undergoing AI therapy for early breast cancer. However, the number of fractures averted through this intervention is small.

A comparative study between the implementation of the FRIDEX calibration and the NOGG guideline in the management of osteoporosis in routine clinical practice. / Estudio comparativo de la aplicación de la calibración FRIDEX y de la guía NOGG en el manejo de la osteoporosis en la práctica clínica habitual.

OBJECTIVE: The recent FRIDEX calibration proposed cost-effectiveness thresholds for the Spanish population. The aim of our study is to evaluate the impact of its application in routine clinical practice and to compare its thresholds with those of the National Osteoporosis Guideline Group (NOGG). MATERIAL AND METHODS: Cross-sectional study in women referred to a bone densitometry unit who were not receiving antiresorptive therapy. The absolute risk of major fracture or hip fracture was calculated with the Spanish and British formulas of the FRAX® tool using the intervention thresholds of the FRIDEX calibration and the NOGG guideline, respectively. RESULTS: The study included 607 women with a median age of 59.4 (IQR=14) years. Treatment was initiated in 31.4% after bone mineral densitometry. With the application of the FRIDEX calibration, bone mineral density testing would have been indicated in 35.4% of the sample and treatment in 26.7%, reducing costs by 18.8% over a 5-year period. The NOGG guideline would have recommended testing in 32% and treatment in 21.3% of the participants, resulting in a reduction in costs of 35% over 5years, when compared with the standard approach. Agreement between the FRIDEX calibration and the NOGG guideline, as defined by Cohen's kappa coefficient, was low in terms of both diagnostic (0.16 [95%CI, 0.09-0.24]) and therapeutic indications (0.39 [95%CI, 0.31-0.47]). CONCLUSIONS: The application of the FRIDEX calibration and the NOGG guideline improves efficiency in the management of osteoporosis, although the level of agreement between the two is low.