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.

Evidence to inform decision makers in Thailand: a cost-effectiveness analysis of screening and treatment strategies for postmenopausal osteoporosis.

OBJECTIVES: To assess value for money of providing systematic screening for osteoporosis among postmenopausal women and medical treatments for those diagnosed with osteoporosis as evidence-based decision making for the revision of the National List of Essential Medicines. METHODS: Decision analytic models were constructed, using a societal perspective, to assess the cost per quality-adjusted life-years (QALYs) gained from systematic screening using the Osteoporosis Self-Assessment Tool and dual-energy X-ray absorptiometry or dual-energy X-ray absorptiometry alone compared with no screening. Alendronate, risedronate, raloxifene, and nasal calcitonin were economically evaluated to determine a treatment of choice for the prevention of osteoporosis-related fractures. Most input parameters were obtained from literature reviews, and systematic reviews and meta-analyses, if available. The service costs and related household expenses were based on the Thai setting. Probabilistic and one-way sensitivity analyses were used to incorporate the impact of parameter uncertainty. RESULTS: The Osteoporosis Self-Assessment Tool and sequential dual-energy X-ray absorptiometry provided better value for money for osteoporosis screening among young age groups (<60 years old). Although there was no significant difference in cost per QALY for older age groups, alendronate provided the lowest incremental cost-effectiveness ratio while nasal calcitonin presented the highest incremental cost-effectiveness ratio. It was shown that providing medication for a secondary prevention yielded a much higher cost per QALY gained compared with providing medication for a primary prevention. CONCLUSIONS: Given the benchmark set at 100,000 Thai baht per QALY gained, providing systematic screening and treatment for osteoporosis was cost-ineffective in the Thai setting.

How rebates, copayments, and administration costs affect the cost-effectiveness of osteoporosis therapies.

PURPOSE: Because of rising drug expenditures, cost considerations have become essential, necessitating the requirement for cost-effectiveness analyses for managed care organizations (MCOs). The study objective is to examine the impact of various drug-cost components, in addition to wholesale acquisition cost (WAC), on the cost-effectiveness of osteoporosis therapies. DESIGN: A Markov model of osteoporosis was used to exemplify different drug cost scenarios. METHODOLOGY: We examined the effect of varying rebates for oral bisphosphonates--risedronate and ibandronate--as well as considering the impact of varying copayments and administration costs for intravenous zoledronate. The population modeled was 1,000 American women, > or = 50 years with osteoporosis. Patients were followed for 1 year to reflect an annual budget review of formularies by MCOs. The cost of therapy was based on an adjusted WAC, and is referred to as net drug cost. The total annual cost incurred by an MCO for each drug regimen was calculated using the net drug cost and fracture cost. We estimated cost on a quality adjusted life year (QALY) basis. PRINCIPAL FINDINGS: When considering different rebates, results for risedronate versus ibandronate vary from cost-savings (i.e., costs less and more effective) to approximately $70,000 per QALY. With no risedronate rebate, an ibandronate rebate of approximately 65% is required before cost per QALY surpasses $50,000. With rebates greater than 25% for risedronate, irrespective of ibandronate rebates, results become cost-saving. Results also showed the magnitude of cost savings to the MCO varied by as much as 65% when considering no administration cost and the highest coinsurance rate for zoledronate. CONCLUSION: Our study showed that cost-effectiveness varies considerably when factors in addition to the WAC are considered. This paper provides recommendations for pharmaceutical manufacturers and MCOs when developing and interpreting such analyses.

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis.

UNLABELLED: Denosumab is an injectable drug that reduces the risk of fractures. The objective was to estimate the cost-effectiveness of denosumab in a Swedish setting, also accounting for poor adherence to treatment. Denosumab is cost-effective, particularly for patients at high risk of fracture and low adherence to oral treatments. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis and osteoporotic fractures that has been shown to reduce the risk of fractures in a phase III trial. The objective of this study was to estimate the cost-effectiveness of denosumab from a societal perspective compared with generic alendronate, branded risedronate, strontium ranelate, and no treatment in a Swedish setting. METHODS: A Markov cohort model was used to estimate the cost-effectiveness of denosumab given for up to 5 years to a typical Swedish patient population (women aged 71 years, T-score ≤ -2.5 SD and a prevalence of morphometric vertebral fractures of 34%). The model included treatment persistence and residual effect after discontinuation assumed to be equal to the time on treatment. Persistence with the comparator treatments and with denosumab was derived from prescription data and a persistence study, respectively. RESULTS: The base-case incremental cost-effectiveness ratios were estimated at €27,000, €12,000, €5,000, and €14,000, for denosumab compared with generic alendronate, risedronate, strontium ranelate, and no treatment, respectively. Sub-optimal persistence had the greatest impact in the comparison with generic alendronate, where the difference in drug cost was large. CONCLUSION: Improving persistence with osteoporosis treatment impacts positively on cost-effectiveness with a larger number of fractures avoided in the population targeted for treatment. Denosumab is a cost-effective alternative to oral osteoporosis treatments, particularly for patients at high risk of fracture and low expected adherence to oral treatments.

The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX.

SUMMARY: The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds. INTRODUCTION: The aim of this study was to assess the cost-effectiveness of risedronate for the prevention and treatment in a UK setting using the FRAX algorithm for fracture risk assessment. A further aim was to establish intervention thresholds with risedronate treatment. METHODS: The cost-effectiveness of risedronate was compared to no treatment in post-menopausal women with clinical risk factors for fracture using a Markov cohort model populated with data relevant for the UK. The model incorporated the features of FRAX (the WHO risk assessment tool). The analysis had a health care perspective and quality adjusted life years was used as the main outcome measure. RESULTS: Treatment was cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds. Treatment was also cost-effective at all ages in women who had previously sustained a fragility fracture or in women with a parental history of hip fracture with a bone mineral density set at the threshold of osteoporosis. At the 30,000 pounds threshold value for a QALY, risedronate was on average found to cost-effective below the 10-year probability of a major osteoporotic fractures of 13.0%. CONCLUSIONS: Risedronate is a cost-effective agent for the treatment of established osteoporosis (osteoporosis and a prior fragility fracture) in women from the age of 50 years and older and above 65 years in women with osteoporosis alone. The results support the treatment recommendations in recent UK guidelines for osteoporosis.

Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: a population-based study.

UNLABELLED: This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) > or = 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. INTRODUCTION: This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. METHODS: A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR > or = 80%) and noncompliant (MPR < 80%) women. RESULTS: Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR > or = 80%: mean difference $17, 95% confidence interval (CI) $2-22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR > or = 80%: mean difference $189, 95% CI $56-320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR > or = 80%: mean difference $-639, 95% CI $-649 to -629. CONCLUSION: Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women>or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

Cost-effectiveness of alternative treatments for women with osteoporosis in Canada.

BACKGROUND: During the years following menopause, estrogen levels decline leading to accelerated bone loss and an increased risk of osteoporosis and osteoporosis-related fractures. METHODS: Using a Markov model and decision analytic techniques, the long-term costs and outcomes of five treatment and secondary prevention strategies for osteoporosis were compared: 'no intervention', alendronate, etidronate, risedronate, and raloxifene. The base case analysis examined postmenopausal (65 year old) osteoporotic women without prior fracture. Probabilistic sensitivity analysis (PSA) was used to incorporate the impact of parameter uncertainty, and deterministic sensitivity analysis (DSA) was used to compare alternative patient populations and modeling assumptions. Life years and Quality Adjusted Life Years (QALYs) were used as measures of effectiveness. RESULTS: In the base case analysis, risedronate was dominated by etidronate and alendronate. Alendronate and etidronate were projected to have similar costs and QALYs, and the efficiency frontier was represented by 'no intervention', etidronate, alendronate, and raloxifene (Can$32 571, Can$38 623 and Can$114 070 per QALY respectively). Alternative assumptions of raloxifene's impact on CHD and breast cancer, alternative discount rates and alternative patient risk factors (e.g., starting age of therapy, CHD risk, and prior fracture risk) had significant impacts on the overall cost-effectiveness results for both the bisphosphonates and raloxifene. DISCUSSION: Using conventionally quoted benchmarks and compared to no therapy, alendronate, etidronate, and raloxifene would all be considered cost-effective alternatives for treating women with osteoporosis. Potential limitations of this study include the usual caveats and cautions associated with long-term projection models and the fact that not all inputs into the model are Canadian data sources.

The cost utility of bisphosphonate treatment in established osteoporosis.

BACKGROUND: Hip fracture is an important and costly problem. Bisphosphonate therapy prevents hip and other fractures among women with established osteoporosis, but there are few published economic evaluations of this treatment. AIM: To assess the cost-effectiveness of risedronate, a recently launched bisphosphonate for the prevention of fractures among women with established osteoporosis. METHODS: A state transition Markov model of established post-menopausal osteoporosis based upon randomized clinical trial data was developed. Uncertainty underlying model parameters and outcomes was dealt with using traditional sensitivity analysis and stochastic sensitivity analysis to produce quasi-95%CIs. We focussed on patients aged approximately 75 years, since this population most closely matches the randomized controlled trial, and is typical of osteoporosis patients in the UK. RESULTS: The baseline model of treating a cohort of 1000 75-year-old women for 3 years with risedronate and then modelling the costs and benefits over their expected lifetimes, produced net savings of pound sterling 786 000 for the treatment group per 1000 treated women, (95%CI pound sterling 1.55m savings to pound sterling 47000 extra costs). Restricting the horizon of the analysis to only three years led to a small net cost of pound sterling 138 000 per 1000 treated women (95%CI pound sterling 196 000 savings to pound sterling 477 000 extra costs) with a net increment in Quality Adjusted Life years (QALYs) of 16 per 1000 treated women. This resulted in a cost per QALY of pound sterling 8625 per treated woman. CONCLUSIONS: In this example, the use of risedronate therapy in 75-year-old women at high risk of hip fracture leads to an improvement in quality of life with possible cost savings. Restricting the analysis to a time horizon of only three years leads to a QALY gain at a modest net cost.

Cost effectiveness of multi-therapy treatment strategies in the prevention of vertebral fractures in postmenopausal women with osteoporosis.

OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of multi-therapy treatment strategies in the prevention of vertebral fractures in postmenopausal women with osteoporosis. DESIGN: A retrospective, incremental cost-effectiveness analysis was conducted from a societal perspective. It compared 9 treatment strategies over 3 years and incorporated the willingness of patients to initiate and continue each therapy. MAIN OUTCOME MEASURES AND RESULTS: Four nondominated strategies formed the efficient frontier in the following order: (i) calcium-->no therapy; (ii) ovarian hormone therapy (OHT)-->calcium-->no therapy [166 Canadian dollars ($Can)]; (iii) OHT-->etidronate-->calcium-->no therapy ($Can2331); and (iv) OHT-->alendronate-->calcium-->no therapy ($Can40,965). The figures in parentheses are the incremental costs per vertebral fracture averted to move to that strategy from the previous strategy for patients who had undergone a hysterectomy. CONCLUSIONS: We identified 4 efficient multi-therapy strategies for the treatment of vertebral osteoporosis in postmenopausal women, 2 of which were consistent with the practice guidelines of the Osteoporosis Society of Canada. Decision-makers may select from among these efficient strategies on the basis of incremental cost effectiveness.

Pharmacoeconomic analysis of osteoporosis treatment with risedronate.

Hip fracture is an important and costly problem. Therapy with the bisphosphonate risedronate effectively prevents hip and other fractures among women with established osteoporosis. Risedronate is a first-choice therapy option in the German Guidelines of the Dachverband Osteologie for Osteoporosis according to evidence-based medicine criteria for the treatment of postmenopausal osteoporosis, osteoporosis of the elderly (women aged > 75 years) and glucocorticoid-induced osteoporosis. There are few published economic evaluations of bisphosphonates in Germany. Therefore, an assessment of the cost-effectiveness of risedronate utilizing a state transition Markov model of established postmenopausal osteoporosis based on randomized clinical trial data was developed. Uncertainty underlying model parameters and outcomes was dealt with using traditional sensitivity analysis and stochastic sensitivity analysis to produce quasi-95% Cls. We focused on patients aged 70 years, since this population most closely matches the randomized controlled trial and is typical of osteoporosis patients in Germany. The baseline model was a cohort of 1,000 70-year-old women, who received risedronate for 3 years and were followed up for an overall observation period of 10 years, modelling transitions through estimated health states and evaluating outcomes. Over the 3-year treatment period and 10-year observation period, risedronate dominated the current average basic treatment in Germany. In the risedronate group 33 hip fractures were averted and 32 quality-adjusted life years (QALYs) were gained (discounted values). Risedronate treatment saves costs for German social insurance: the present net value of the associated costs from the perspective of German social insurance is [symbol: see text]10.66 million if risedronate treatment is used versus [symbol: see text]11 million if basic treatment is used. Thus, net savings of [symbol: see text]340,000 for the treatment group per 1,000 treated women were calculated. Furthermore, risedronate treatment is cost effective from the perspective of the statutory health insurance with costs per averted hip fracture in the analyzed population of [symbol: see text]33,856 and cost per QALY gained of [symbol: see text]35,690. Both results demonstrate cost-effectiveness and are far below the accepted threshold level of [symbol: see text]50,000. Based on this analysis, risedronate is a cost-effective treatment for postmenopausal osteoporosis within the German health care system, offering benefits for osteoporotic patients and for budget decision-makers.

Health-economic comparison of three recommended drugs for the treatment of osteoporosis.

Osteoporosis is a large and growing disease with significant health consequences. Based on an evaluation of clinical evidence, the German osteology umbrella organization DVO (Dachverband Osteologie deutschsprachiger wissenschaftlicher Fachgesellschaften) published guidelines in March 2003 for the diagnosis and treatment of osteoporosis. For prevention of fractures in women with postmenopausal and senile osteoporosis, these guidelines recommend three treatment options as first-line therapy: risedronate, alendronate and raloxifene. No evidence is currently available for the reduction of hip fractures by raloxifene. Only risedronate and alendronate, therefore, are recommended for prevention of hip fractures. Information on the cost-effectiveness of preventing and treating osteoporosis may support decision makers in more efficient allocation of resources. Accordingly, the objective of this study is the comparative assessment of the cost-effectiveness of risedronate, alendronate and raloxifene for patient populations in Germany at high risk of osteoporotic fracture due to low bone mineral density (BMD) (i.e., T-score < -2.5) and resulting from a history of at least one previous vertebral fracture, as compared to osteoporotic patients with no treatment. Target variables for the economic comparison are costs per hip fracture avoided and costs per quality-adjusted life year (QALY) gained. Hip fractures are the most costly and best-documented complication of osteoporosis. A cost-effectiveness analysis was therefore conducted, using as criteria for evaluating intervention the incremental cost per hip fracture avoided and the cost per QALY gained. We used a fracture-incidence-based Markov model of osteoporosis, with analysis of patients' transition across outcome states over time (e.g., fracture, healthy, dead). Base-case analysis was conducted on a cohort of 1,000 women aged 70 with low spine BMD and prevalent vertebral fracture, over 3 years of treatment with risedronate, alendronate or raloxifene, and with application of a 10-year analytic time horizon. Model inputs included hip and vertebral fracture incidence rates; relative risk of fracture given low BMD and prevalent vertebral fracture, fracture cost, treatment prices/day (risedronate: 35 mg, 1.76 euro; alendronate: 70 mg, 1.82 euro; raloxifene: 60 mg, 1.82 euro); health utility; and efficacy in terms of relative-risk reduction of fracture of the hip (60% risedronate; 51% alendronate; not significant raloxifene) and vertebrae (49% risedronate; 47% alendronate; 30% raloxifene). A 5% discount rate was applied to cost and outcomes. In the base case, treatment with risedronate reduces costs from the social insurance perspective with respect to both endpoints: i.e., costs per averted hip fracture and QALY. Over the 3-year treatment period and 10-year observation, furthermore, risedronate proved superior to alendronate and raloxifene (i.e., risedronate was less expensive and more effective). From the perspective of statutory health insurance, the cost per averted hip fracture is 37,348 euro for risedronate and 48,349 euro for alendronate (costs for raloxifene were not calculated due to a nonsignificant effect on prevention of hip fractures); and cost per QALY gained is 32,092 euro for risedronate, in comparison to patients in Germany with no therapy (alendronate 41,302 euro; raloxifene 1,247,119 euro). This cost-effectiveness analysis gives evidence that bisphosphonates are cost effective. Under consideration of current prices and the published clinical evidence, risedronate dominates the comparison of DVO-recommended drugs.

Risedronate prevents hip fractures, but who should get therapy?

The Hip Intervention Program (HIP) trial establishes that risedronate (Actonel) prevents hip fracture in elderly women with osteoporosis. However, the drug had no statistically significant effect on hip fracture risk in elderly women in whom bone density status was not known. Patients should be selected for bisphosphonate therapy on the basis of low bone density. A history of vertebral fractures increases the risk for hip fractures.

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.

Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada.

OBJECTIVE: Denosumab is a novel biologic agent approved in Canada for treatment of post-menopausal osteoporosis (PMO) in women at high risk for fracture or who have failed or are intolerant to other osteoporosis therapies. This study estimated cost-effectiveness of denosumab vs usual care from the perspective of the Ontario public payer. METHODS: A previously published PMO Markov cohort model was adapted for Canada to estimate cost-effectiveness of denosumab. The primary analysis included women with demographic characteristics similar to those from the pivotal phase III denosumab PMO trial (FREEDOM; age 72 years, femoral neck BMD T-score -2.16 SD, vertebral fracture prevalence 23.6%). Three additional scenario sub-groups were examined including women: (1) at high fracture risk, defined in FREEDOM as having at least two of three risk factors (age 70+; T-score ≤ -3.0 SD at lumbar spine, total hip, or femoral neck; prevalent vertebral fracture); (2) age 75+; and (3) intolerant or contraindicated to oral bisphosphonates (BPs). Analyses were conducted over a lifetime horizon comparing denosumab to usual care ('no therapy', alendronate, risedronate, or raloxifene [sub-group 3 only]). The analysis considered treatment-specific persistence and post-discontinuation residual efficacy, as well as treatment-specific adverse events. Both deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The multi-therapy comparisons resulted in incremental cost-effectiveness ratios for denosumab vs alendronate of $60,266 (2010 CDN$) (primary analysis) and $27,287 per quality-adjusted life year gained for scenario sub-group 1. Denosumab dominated all therapies in the remaining scenarios. LIMITATIONS: Key limitations include a lack of long-term, real-world, Canadian data on persistence with denosumab as well as an absence of head-to-head clinical data, leaving one to rely on meta-analyses based on trials comparing treatment to placebo. CONCLUSIONS: Denosumab may be cost-effective compared to oral PMO treatments for women at high risk of fractures and those who are intolerant and/or contraindicated to oral BPs.

Analysis of the comparative effectiveness of 3 oral bisphosphonates in a large managed care organization: adherence, fracture rates, and all-cause cost.

BACKGROUND: Despite widespread availability and use of oral bisphosphonates, fracture rates and associated medical costs are still high. Differences in fracture risk among these agents, if any, have not been quantified due to the lack of high-quality, head-to-head, randomized, controlled trials assessing this outcome. Randomized, placebo-controlled trials have shown that alendronate and risedronate reduce rates of both vertebral and nonvertebral fractures, whereas only reduction in vertebral fractures has been found for ibandronate. OBJECTIVE: To determine if there were any differences among 3 oral bisphosphonates in adherence, total cost of care, and effectiveness in reducing fracture rates in a large managed care population. METHODS: Administrative, longitudinal pharmacy and medical claims data were obtained from 14 geographically diverse health plans in the United States covering approximately 14 million members. Sampled members had at least 1 pharmacy claim for alendronate, risedronate, or ibandronate during the intake period (January 1, 2005, through October 31, 2007). The date of the first pharmacy claim for osteoporosis medications within the intake period was the index date. Members were followed for either 12, 24, or 36 months, depending on length of continuous health plan eligibility. Medication possession ratio (MPR) was measured using a total days supply that was calculated by multiplying the total quantity dispensed by the suggested days supply per unit of dispensing based on manufacturer-recommended dosing. For members who switched bisphosphonate strengths or medications, the estimated days supply was summed for all osteoporosis medications during the follow-up, including overlapping days supply. Outcomes included (a) the first incident fracture and percentages of members with at least 1 fracture after 6 months post-index; (b) the number of days from index to the first incident fracture, measured as time to event in Cox proportional hazards regression analysis; and (c) total all-cause health care costs (health plan allowed amount including member cost share). RESULTS: A total of 45,939 members were included (n = 24,909 alendronate, n = 13,834 risedronate, n = 7,196 ibandronate). In the 12-month analysis, MPRs were comparable (means = 0.57-0.58) for the 3 medications. After 24 months, MPRs had dropped for all medications, but those of both alendronate (mean = 0.50, 95% CI = 0.49-0.50) and risedronate (mean = 0.50, 95% CI = 0.49-0.51) were slightly higher than that of ibandronate (mean = 0.47, 95% CI = 0.46-0.48). At 36 months, again the MPRs had dropped for all 3 medications (means = 0.44-0.47) but were similar. There were no statistically significant differences among agents in the percentages of subjects with at least 1 fracture at 12, 24, or 36 months (36-month rates: alendronate 4.41%, risedronate 4.38%, ibandronate 6.28%, P = 0.102). The numbers of subjects with fracture(s) per month of follow-up were 0.0020 for alendronate, 0.0021 for risedronate, and 0.0022 for ibandronate (P = 0.087 overall). However, after adjusting for member characteristics, alendronate users had a 12% lower risk of experiencing any incident fracture than ibandronate users (hazard ratio = 0.88, 95% CI = 0.78-0.99, P = 0.034) within the follow-up period. In the first 12 post-index months, ibandronate users had higher mean [SD] unadjusted total all-cause health care costs ($7,464 [$15,975]) compared with alendronate ($7,233 [$16,671]) and risedronate ($ 6,983 [$16,870], P less than 0.001 for both comparisons), differences of approximately $19 per month and $40 per month, respectively. The results of the unadjusted 24-month analysis were similar, but there were no significant cost differences at 36 months. Total cost differences for the 3 medication groups were nonsignificant at 12, 24, and 36 months after adjusting for member characteristics. CONCLUSIONS: This retrospective analysis of an administrative claims database in a large managed care population showed similar rates of adherence and total adjusted all-cause health care costs for alendronate, risedronate, and ibandronate. Absolute unadjusted rates of fracture were small and did not significantly differ among agents, but after controlling for differences in member characteristics, the risk of fracture was 12% lower for alendronate users than for ibandronate users.

Cost-effectiveness of strontium ranelate versus risedronate in the treatment of postmenopausal osteoporotic women aged over 75 years.

OBJECTIVE: To estimate the cost-effectiveness of strontium ranelate in the treatment of postmenopausal osteoporotic women aged over 75 years. MATERIALS AND METHODS: A validated Markov microsimulation model with a Belgian payer's perspective estimated the cost per quality-adjusted life-year (QALY) of a 3-year strontium ranelate treatment compared with no treatment and with the bisphosphonate risedronate. Data on the effect of both treatments on fracture risk were taken from the Cochrane Database of Systematic Reviews. Analyses were performed for postmenopausal women aged 75 and 80 years, either with a diagnosis of osteoporosis (i.e. bone mineral density T-score

Risedronate versus alendronate in older patients with osteoporosis at high risk of fracture: an Italian cost-effectiveness analysis.

BACKGROUND AND AIMS: This evaluation of the cost-effectiveness of risedronate vs generic alendronate is based on effectiveness data from a large real practice study. Applying a published cost-effectiveness model, we found that risedronate is cost-effective vs generic alendronate in an Italian population aged > or =65 years, and becomes dominant, saving costs and avoiding fractures, in patients aged > or =75 years. The aim of this work was to assess the cost-effectiveness and health utility of risedronate vs generic alendronate in clinical practice in Italy, using effectiveness data from the REAL study. METHODS: A pre-existing model of osteoporosis was used to predict numbers of fractures, quality-adjusted life-years (QALYs), and costs associated with risedronate or alendronate treatment in post-menopausal (PMO) women aged > or =65 years with a previous vertebral fracture, within the Italian National Health System (NHS). Duration of treatment with risedronate or alendronate was assumed to occur for one year and patients were followed for an additional five years to capture longterm costs and outcomes, with a discount rate of 3% for costs and outcomes. Comprehensive sensitivity analyses were run. RESULTS: The lower fracture rate among risedronate patients with respect to alendronate patients resulted in savings of euro 19,083, a reduction of 8.91 hip fractures and an associated benefit of 7.46 QALYs, in an Italian cohort of 1,000 patients. Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: This economic analysis showed that risedronate is a cost-effective treatment in a population of Italian women aged 65 years and older at high risk of PMO-related fractures. Risedronate becomes dominant over generic alendronate in patients of 75 years or older and its cost-effectiveness even appears improved in patients with BMD score < or = -3 or < or = -3.5, with/without maternal history of fractures. Risedronate should be considered as a cost-effective option vs generic alendronate, in the Italian NHS' perspective.