Cost-effectiveness of sequential treatment with abaloparatide followed by alendronate vs. alendronate monotherapy in women at increased risk of fracture: A US payer perspective.

OBJECTIVES: Emerging evidence supports sequential therapy with anabolic followed by antiresorptive in patients at high-risk of fragility fractures. This study assessed the cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) [(ABL/ALN)] compared to ALN monotherapy and to sequential treatment starting with antiresorptive therapy (ALN/ABL/ALN). METHODS: A previously validated Markov microsimulation model was used to estimate the cost-effectiveness of sequential ABL/ALN compared to ALN monotherapy and to sequential ALN/ABL/ALN from a lifetime US payer perspective. In line with practice guidelines, patients were assumed to receive ABL for 18 months followed by 5 years of ALN, or ALN monotherapy for 5 years, or a sequence of ALN for 2 years followed by 18 months of ABL and then by 3 years ALN. Evaluation was conducted for patients aged 50-80 years old with a BMD T-score ≤-3.5 and without a history of prior fracture, or with a T-score between -2.5 and -3.5 and a history of ≥ 1 osteoporotic fracture. RESULTS: Sequential ABL/ALN was cost-effective (threshold of US$150,000 per QALY) vs generic ALN monotherapy in women ≥60 years with a BMD T-score ≤-3.5 and in women with BMD T-score between -2.5 and -3.5 and history of osteoporotic fracture. In all simulated populations, sequential ABL/ALN therapy was dominant (lower costs, more QALYs) compared with sequential ALN/ABL/ALN, resulting from limited effect of ABL in patients previously treated with an antiresorptive agent. CONCLUSIONS: Sequential ABL/ALN therapy is cost-effective vs ALN monotherapy for US postmenopausal women aged ≥60 years at increased risk of fractures.

Cost-effectiveness of five versus ten years of alendronate treatment prior to drug holiday for women with osteoporosis.

We performed a cost-effectiveness analysis comparing 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for US postmenopausal women with hip BMD T-scores between - 2.5 and - 3.5. We found that for most postmenopausal women 5 years of treatment prior to drug holiday is the more effective and cost-effective option. INTRODUCTION: We performed a cost-effectiveness analysis to compare 5 versus 10 years of alendronate treatment prior to 5-year drug holiday for postmenopausal osteoporotic women. METHODS: We created an individual-level state-transition microsimulation model to compare 3 treatment strategies for US postmenopausal women with osteoporosis and femoral neck BMD T-scores between - 2.5 and - 3.5 at baseline: recurrent periods of 5 years of alendronate followed by 5 years of drug holiday (alendronate 5/5), recurrent periods of 10 years of alendronate followed by 5 years of drug holiday (alendronate 10/5), and no alendronate treatment. RESULTS: Base-case analysis revealed for women initiating treatment at ages 50, 60, and 70, the alendronate 5/5 strategy dominated (was more effective and less costly than) the alendronate 10/5 strategy and no treatment. For women age 80, the alendronate 10/5 strategy dominated. When assuming a lower relative risk of nonvertebral fracture during years 6-10 of alendronate treatment than the base-case assumption, the alendronate 10/5 strategy became the most cost-effective strategy even at younger treatment initiation ages. Probabilistic sensitivity analysis results supported the base-case findings; for treatment initiation ages of 50, 60, and 70, the alendronate 5/5 strategy was favored, whereas for treatment initiation age of 80, the alendronate 10/5 strategy was favored; however, there was uncertainty in these findings. CONCLUSIONS: After 5 years of alendronate treatment, younger postmenopausal women (ages 50-70) with osteoporosis would likely benefit from a drug holiday, whereas older women (age 80) are likely to benefit from treatment for 10 years before a drug holiday.

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.

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.

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.

Establishing and evaluating FRAX® probability thresholds in Taiwan.

BACKGROUND/PURPOSE: The Taiwanese FRAX® calculator was launched in 2010. However, cost-effectiveness thresholds for the prescription of antiosteoporosis medications were not established. This study aims to establish and evaluate FRAX®-based probability thresholds in Taiwan. METHODS: Using previous data from Taiwan and literature, we determined cost-effectiveness thresholds for prevention of osteoporotic fractures by alendronate with a Markov model, as well as using two other translational approaches. Sensitivity analysis was applied using different alendronate prices. A clinical sample was used to test these Taiwan-specific thresholds by determining the percentages of high-risk patients who would be qualified for current National Health Insurance reimbursement. RESULTS: With the Markov model, the intervention threshold for hip fracture was 7% for women and 6% for men; for major osteoporotic fracture, it was 15% for women and 12.5% for men. Both translational approach models were cost effective only for certain age groups. However, if branded alendronate was reimbursed at 60% of the current price, they became cost effective in almost all age groups. This clinical screening study showed that the National Health Insurance Administration model identified the highest proportion (44%) of patients qualified for National Health Insurance reimbursements, followed by the Markov model (30%), and the United States model (22%). CONCLUSION: Three FRAX®-based models of alendronate use were established in Taiwan to help optimize treatment strategies. The government is encouraged to incorporate FRAX®-based approaches into the reimbursement policy for antiosteoporosis medicines.

A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. METHODS: A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. CONCLUSIONS: In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for postmenopausal Japanese women over 60 years. In terms of cost-effectiveness, the individual need for osteoporosis screening should be determined by age and clinical risk factors.

A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures.

BACKGROUND: Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. OBJECTIVES: To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. DATA SOURCES: For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. REVIEW METHODS: A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. RESULTS: Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. LIMITATIONS: We assumed that all treatment strategies are viable alternatives across the whole population. CONCLUSIONS: Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006883. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

[Bisphosphonate use and related pharmaceutical issues II]. / A biszfoszfonátok alkalmazásának gyakorlata és aktuális gyógyszerészeti vonatkozásai II.

UNLABELLED: Bisphosphonates have basic role in decreasing progression of malignant bone processes as well as in the prevention and therapy of osteoporosis. Use of bisphosphonates is common in Hungary since 20 years. In the past decade their reimbursement has been changed several times, the use of generics decreased the price of bisphosphonates. In this paper we analyze the consumption of prescribed bisphosphonates in Hungary. DATA: Prescription data of the National Health Insurance Fund of Hungary. METHOD: We analysed the prescribed bisphosphonates between 2006-2014. We examined the type and amount of bisphosphonates used by years. After identifying therapy areas of use, we calculated the years of therapy from the DOT data. From this data we estimated the mean bisphosphonate therapy costs and costs falling for the patients. Changes in the reimbursement system regarding these medications was analysed. RESULTS: Bisphosphonate years of therapy was decreasing in osteoporosis over the 9 years examined. In oncology bisphosphonate use shows stability in drug consumption. In both therapeutic areas the proportion in therapy choice of specific bisphosphonates has changed. Bisphosphonate reimbursement costs paid by the Hungarian reimbursement system was approx. 8 billion HUF in osteoporosis and 4,7 billion HUF in oncology in 2006. Changes of the reimbursement strategy, the compulsory generic use and decreasing consumption in osteoporosis has significantly reduced the overall costs by 2014. CONCLUSION: According to our results bisphpsphonate use in oncology is moderate in Hungary, a decreasing consumption can be detected in osteoporosis, that is still expected to decrease. The use of generics reduced bisphosphonate therapy costs and also overall health care costs. In osteoporosis patients cost have substantially lowered.

Cost-effectiveness analysis of treatment of osteoporotic fractures in relation to FRAX algorithm in a sample of Polish population.

BACKGROUND: The increasing incidence of osteoporotic fractures is becoming a growing burden on the health service. Due to the high cost of treatment, these fractures require a broader look at the underlying problem. The aim of the study was to assess the 10-year probability of hip fracture or any other major osteoporotic fracture at which the treatment becomes cost-effective. MATERIAL AND METHODS: This was a retrospective study of a group of 1,024 patients. The cost-effectiveness of pharmacological low-energy fracture prevention was analyzed by means of the medication defined as the reimbursement limit basis in the reimbursement limit group 147.0. (medications used in bone diseases) in July 2013 (Alendrogen 70 mg). 3- and 5-year therapies were analysed. The outcome was compared with the results of FRAX® (of the Polish and British population) in every patient. RESULTS: The model for calculating cost-effectiveness showed that treatment after the age of 50 until the age of 60-65 years is cost-effective at a similar level of 10-year major fracture probability (regardless of treatment duration). After the age of 65, there is a clear decline in the profitability of the therapy. The results indicate that, for the population of women aged >50 years, the treatment is cost-effective when the 10-year major fracture probability equals 5.1% and 6% for a 3- and 5-year therapy, respectively. CONCLUSIONS: 1. The study showed pharmacological treatment to be cost-effective in a large group of patients forming the study population. 2. The analysis also revealed a strong correlation between study results and the specific tool employed to define fracture probability.

Bridging the osteoporosis treatment gap: performance and cost-effectiveness of a fracture liaison service.

Individuals who sustain fragility fractures are at high risk of refracture. However, osteoporosis treatment rates remain low for these patients. Therefore, we aimed to assess the performance and cost-effectiveness of introducing a fracture liaison service (FLS) into a tertiary hospital. In "nonhospitalized" ambulatory patients who had sustained fragility fractures, we assessed baseline osteoporosis investigation and treatment rates, and subsequently, the impact of introducing an orthopedic osteoporosis policy and an FLS. Outcomes measured were uptake of osteoporosis intervention, patient satisfaction, and quality-adjusted life years (QALYs) gained. QALYs were calculated over 5 years using predicted fracture risks without intervention and estimated fracture risk reduction with intervention. At baseline (n = 49), 2% of ambulatory patients who had sustained fragility fractures underwent dual-energy X-ray absorptiometry (DXA) and 6% received osteoporosis-specific medication. After introduction of an osteoporosis policy (n = 58), 28% were investigated with DXA (p < 0.0001). However, treatment rates were unchanged. An FLS was introduced, reviewing 203 new patients over the inaugural 2 years (mean age [standard deviation], 67 (11) years; 77% female). All underwent DXA, and criteria for osteoporosis and osteopenia were identified in 44% and 40%, respectively. Osteoporosis medications were prescribed to 61% patients (risedronate: 22%, alendronate: 16%, strontium ranelate: 13%, zoledronic acid: 8%, other: 2%). Eighty-five of 90 questionnaire respondents were very satisfied or satisfied with the FLS. With the treatment prescribed over 5 years, we conservatively estimated that this FLS would reduce nonvertebral refractures from 59 to 50, improving QALYs by 0.054 and costing $1716 per patient (incremental cost-effectiveness ratio: $31749). This FLS model improves uptake of osteoporosis intervention guidelines, is popular among patients, and improves cost-effectiveness. Thus, it has the capacity to substantially improve health in a cost-effective way.

Cost-minimization study comparing annual infusion of zoledronic acid or weekly oral alendronate in women with low bone mineral density.

Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p<0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance.

[Public spending on drugs for the treatment of osteoporosis in post-menopause]. / Gastos públicos com medicamentos para o tratamento da osteoporose na pós-menopausa.

OBJECTIVE: To analyze expenditure on treatment for postmenopausal osteoporosis and associated factors on mean per capita expenditure. METHODS: A probabilistic-deterministic linkage between the database of Authorizations for Highly Complex Procedures and the mortality information system was constructed, resulting in a historical cohort of patients using high-cost medications for the treatment of postmenopausal osteoporosis, between 2000-2006. Mean monthly spending on medicines was stratified by age group and described according to demographic and clinical characteristics and the type of drug used. A linear regression model was used to assess the impact of demographic and clinical characteristics on per capita mean monthly expenditure on medicines. RESULTS: We identified 72,265 women who received drugs for the treatment of postmenopausal osteoporosis. The average monthly expenditure per capita in the first year of treatment was $ 54.02 (sd $ 86.72). The population was predominantly composed of women aged 60-69 years old, who had started treatment in 2000, resident in the Southeast of Brazil, who had previously suffered osteoporotic fractures, and Alendronate sodium was the drug most commonly used at baseline. For most of the patients, the same active ingredient remained in use throughout the treatment period. During the program, 6,429 deaths were identified among participants. More than a third of women remained in treatment for up to 12 months. Raloxifen and calcitonin were the therapeutic alternatives with the greatest impact on the average monthly expenditure on medicine using alendronate sodium as a reference standard. CONCLUSIONS: Due to the high impact of the type of drug used on expenditure on medication, it is recommended that criteria for prescribing and dispensing be established by prioritizing those with lower costs and greater effectiveness in order to optimize the process of pharmaceutical care and provide the population with a greater number of pharmaceutical units.

Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US.

BACKGROUND: In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE: The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. METHODS: A lifetime cohort Markov model was developed with seven health states: 'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. RESULTS: In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. CONCLUSION: In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.

Gastos publicos com medicamentos para o tratamento da osteoporose na pos-menopausa / Public spending on drugs for the treatment of osteoporosis in post-menopause / Gastos con medicamentos en el Sistema Unico de Salud para el tratamiento de la osteoporosis en la post-menopausia

OBJETIVO: Analisar os gastos com medicamentos para o tratamento da osteoporose na pós-menopausa e os fatores associados ao gasto médio per capita . MÉTODOS: Pareamento probabilístico-determinístico a partir das bases das Autorizações de Procedimentos de Alta Complexidade com o Sistema de Informação sobre Mortalidade, resultando em coorte histórica de pacientes que utilizaram medicamentos de alto custo para o tratamento da osteoporose na pós-menopausa de 2000 a 2006. O gasto médio mensal com medicamentos foi estratificado por faixas etárias e descrito de acordo com as características demográficas, clínicas e tipo de medicamento utilizado. Foi utilizado modelo de regressão linear para avaliar o impacto de características demográficas e clínicas sobre o gasto médio mensal per capita com os medicamentos. RESULTADOS: Foram identificadas 72.265 mulheres que receberam medicamentos para o tratamento da osteoporose na pós-menopausa. O gasto médio mensal per capita no primeiro ano de tratamento foi de R$ 90,00 (dp R$ 144,49). A maioria das mulheres tinha de 60 a 69 anos de idade, iniciaram tratamento em 2000, eram residentes na região Sudeste, tinham fraturas osteoporóticas prévias e o alendronato de sódio foi o medicamento mais utilizado no início do tratamento. A maioria das pacientes permaneceu em uso do mesmo princípio ativo durante o tratamento. Foram identificados 6.429 óbitos entre as participantes. Mais de um terço das mulheres permaneceram no programa por até 12 meses. Raloxifeno e calcitonina sintética foram as alternativas com maior impacto sobre o gasto médio mensal com medicamentos, tendo como padrão de referência o ...

OBJECTIVE: To analyze expenditure on treatment for postmenopausal osteoporosis and associated factors on mean per capita expenditure. METHODS: A probabilistic-deterministic linkage between the database of Authorizations for Highly Complex Procedures and the mortality information system was constructed, resulting in a historical cohort of patients using high-cost medications for the treatment of postmenopausal osteoporosis, between 2000-2006. Mean monthly spending on medicines was stratified by age group and described according to demographic and clinical characteristics and the type of drug used. A linear regression model was used to assess the impact of demographic and clinical characteristics on per capita mean monthly expenditure on medicines. RESULTS: We identified 72,265 women who received drugs for the treatment of postmenopausal osteoporosis. The average monthly expenditure per capita in the first year of treatment was $ 54.02 (sd $ 86.72). The population was predominantly composed of women aged 60-69 years old, who had started treatment in 2000, resident in the Southeast of Brazil, who had previously suffered osteoporotic fractures, and Alendronate sodium was the drug most commonly used at baseline. For most of the patients, the same active ingredient remained in use throughout the treatment period. During the program, 6,429 deaths were identified among participants. More than a third of women remained in treatment for up to 12 months. Raloxifen and calcitonin were the therapeutic alternatives with the greatest impact on the average monthly expenditure on medicine using alendronate sodium as a reference standard. CONCLUSIONS: Due to the high impact of the type of drug used on expenditure on medication, it is recommended that criteria for prescribing and dispensing ...

OBJETIVO: Analizar los gastos con medicamentos para el tratamiento de la osteoporosis en la post-menopausia y los factores asociados al gasto promedio per cápita. MÉTODOS: Pareamiento probabilístico-deterministico a partir de las bases de las Autorizaciones de Procedimientos de Alta Complejidad con el Sistema de Información sobre Mortalidad, resultando en cohorte histórica de pacientes que utilizaron medicamentos de alto costo para el tratamiento de la osteoporosis en la post-menopausia de 2000 a 2006. El gasto promedio mensual con medicamentos fue estratificado por grupos etarios y descrito de acuerdo con las características demográficas, clínicas y tipo de medicamento usado. Se utilizó modelo de regresión linear para evaluar el impacto de las características socio demográficas y clínicas sobre el gasto promedio mensual per cápita con los medicamentos. RESULTADOS: Se identificaron 72.265 mujeres que recibieron medicamentos para el tratamiento de la osteoporosis en la post-menopausia. El gasto promedio mensual per cápita en el primer año de tratamiento fue de R$ 90,00 (de R$ 144,49). La mayoría de las mujeres tenía de 60 a 69 años de edad, iniciaron tratamiento en 2000, eran residentes en la región Sureste, tenían fracturas osteoporóticas previas, y el alendronato de sodio fue el medicamento más utilizado en el inicio del tratamiento. La mayoría de los pacientes permaneció en uso del mismo principio activo durante el tratamiento. Se identificaron 6.429 óbitos entre las participantes. Más de un tercio de las mujeres permanecieron en el programa por 12 meses. Raloxifeno y calcitonina sintética fueron las alternativas con mayor impacto sobre el gasto promedio mensual con medicamentos, teniendo como patrón de referencia ...

Cost-effectiveness of osteoporosis interventions for 'incidental' vertebral fractures.

BACKGROUND: Vertebral fractures detected "incidentally" by chest radiograph usually do not trigger osteoporosis treatment in older patients. In a 3-arm controlled trial we reported that both physician-directed and enhanced (physician plus patient activation) interventions increased treatment rates more than 10-fold (15%-20% absolute increases) compared with usual care; the cost-effectiveness of these interventions is unknown. METHODS: Incremental cost-effectiveness of these 2 interventions compared with usual care was assessed using a Markov decision-analytic model, populated with 1-year outcomes data and direct intervention costs from the trial. Costs were expressed in 2009 Canadian dollars and effectiveness based on quality-adjusted life years (QALYs) gained. The perspective was health care payer; horizon was projected lifetime; costs and benefits were discounted at 3%; and deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Per patient, the physician and enhanced interventions cost $34 and $42, respectively. Compared with usual care, for every 1000 patients exposed to the physican intervention there were 4 fewer fractures, 8 more QALYs gained, and $282,000 saved. Compared with physician interventions, for every 1000 patients exposed to enhanced interventions there were 6 fewer fractures, 6 more QALYs gained, and $339,000 saved. Both interventions dominated usual care and were cost-effective in ~80% of 10,000 probabilistic simulations. Although the enhanced intervention cost $8 more per patient, it still dominated the physician intervention and usual care, and was the most economically attractive option. CONCLUSIONS: Pragmatic and inexpensive interventions directed at patients with incidentally detected vertebral fractures and their physicians are highly cost-effective at improving osteoporosis treatment, and in most circumstances also are cost-saving.