Generic Alendronate Research Articles

Efficacy and Safety of Generic Alendronate for Osteoporosis Treatment.

While osteoporosis increases the risk of fragility fractures, bisphosphonate has been proven to increase bone strength and reduce the risk of vertebral and non-vertebral fractures. In addition to its efficacy, substituting the brand with generic medication is a strategy to optimize healthcare expenditures. This study aimed to evaluate the efficacy of generic alendronate treatment and assess potential adverse events in patients with osteoporosis. A retrospective review was conducted on 120 patients who met the indications for osteoporosis treatment, received weekly generic alendronate (70 mg) for >1 year, and underwent evaluation through standard axial dual-energy X-ray absorptiometry (DXA). The outcomes of this study were the percent change in bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip after one year of treatment. The major adverse events occurring during medication that led to the discontinuation of drug administration were documented. Most patients were female (96.7%) with an average age of 69.0 ± 9.3 years. The percent change in BMD increased at all sites after one year of generic alendronate treatment (lumbar spine: 5.6 ± 13.7, p-value <0.001; femoral neck: 2.3 ± 8.3, p-value = 0.023; total hip: 2.1 ± 6.2, p-value = 0.003), with over 85% of patients experiencing increased or stable BMD. Three patients discontinued the medication due to adverse effects: two had dyspepsia, and one had persistent myalgia. Generic alendronate may be considered an effective antiresorptive agent for osteoporosis treatment with a low incidence of adverse effects.

PMS12 Cost-Effectiveness of Binosto (BUFFERED SOLUBLE ALENDRONATE 70 MG) Effervescent Tablet for the Treatment of Postmenopausal Women with Osteoporosis in Italy

Binosto® (buffered soluble alendronate 70 mg) effervescent tablet represents an alternative option to traditional oral bisphosphonates for the management of osteoporosis, being associated to a lower frequency of gastro-intestinal adverse reactions and greater medication persistence. This study aimed to assess the cost-effectiveness of Binosto® compared with relevant alternative treatments for postmenopausal osteoporotic women in Italy. A previously validated Markov microsimulation model was adjusted to the Italian healthcare setting to estimate the lifetime costs (expressed in €2019) per quality-adjusted life-years (QALY) of Binosto® compared with generic alendronate, denosumab, zoledronic acid and no treatment. Pooled efficacy data for bisphosphonates derived from the most recent NICE network meta-analysis were used for bisphosphonate treatments and 1-year persistence of Binosto® and alendronate was derived from a prospective observational study. Analyses were conducted for high-risk women 60-80 years of age with a bone mineral density (BMD) T-score ≤-3.0 or with existing vertebral fractures. One-way and probabilistic sensitivity analyses were performed to test the robustness of the model results. In all simulated populations, Binosto® was dominant (more QALYs, less costs) compared to denosumab. The cost per QALY gained of Binosto® compared to generic alendronate and no treatment always fall below €20,000 per QALY gained. Zoledronic acid was associated with more QALY than Binosto® but the cost per QALY gained of zoledronic acid compared with Binosto® was always higher than €70,000 per QALY gained, meaning that zoledronic acid was not cost-effective. Probabilistic sensitivity analyses suggested that Binosto® was the most cost-effective intervention for willingness to pay between €5,000 and €75,000 per QALY gained. This study provides the first economic analysis of an alendronate effervescent tablet, suggesting that Binosto® represents a cost-effective strategy compared with relevant alternative treatments for postmenopausal women with osteoporosis in Italy aged 60 years and over.

Cost-effectiveness of FRAX\xae-based intervention thresholds for management of osteoporosis in Singaporean women

SummaryCost-effectiveness analysis of FRAX® intervention thresholds (ITs) in Singaporean women > 50 years of age showed that generic alendronate was cost-effective at age-dependent major osteoporotic fracture (MOF) IT from the ages of 65 years for both full and real-world adherence whilst hip fracture (HF) ITs were cost-effective from the ages of 60 and 65 years. Alendronate was cost-effective irrespective of age only at fixed MOF IT of 14% and HF IT of 3.5%.IntroductionFRAX®-based intervention thresholds (ITs) were recently identified for osteoporosis management in Singapore. This study aimed to assess the cost-effectiveness of ITs in Singaporean women over the age of 50 years.MethodsA validated Markov microsimulation model was used to estimate the lifetime healthcare costs (SGD2019) per quality-adjusted life-years (QALY) of generic alendronate compared with no treatment. Cost-effectiveness of age-dependent FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) ITs was explored. In addition, ITs that would lead to cost-effectiveness were computed. Fracture incidence and cost data were obtained from the Ministry of Health and a previously published Singaporean study. A cost-effectiveness threshold of SGD 62,500/QALY gained was used, based conservatively on 0.7 times the Singapore GDP per capita.ResultsGeneric alendronate was shown to be cost-effective at MOF ITs from the ages of 65 years, while HF ITs were cost-effective from the ages of 60 and 65 years, assuming full and real-world adherence, respectively. A 14% MOF and a 3.5% HF ITs were required for alendronate to be cost-effective above 50 years.ConclusionThis study suggests that the treatment of Singaporean women with alendronate is cost-effective at age-dependant FRAX® intervention thresholds at 65 years and older. Furthermore, identifying women at any age above 50 years with a 10-year risk of MOF or HF of 14% or 3.5% would lead to efficient use of resources. Cost-effective access to therapy for patients at high fracture probability based on FRAX® could contribute to reduce the growing burden of osteoporotic fractures in Singapore.

Bone mineral density status and the need for anti-osteoporotic therapy in postmenopausal women with systemic scleroderma

The article is devoted to the study of bone mineral density in patients with systemic scleroderma (SSD) and the identification of persons, who needs the anti-osteoporotic treatment. A total of 170 postmenopausal women were examined: 103 patients with SSD and 67 patients without inflammatory rheumatic diseases. Osteoporosis (OP) was detected in 49.5% in the patient group and in 31% in the control group (p &lt;0.05). The correlation relation between the bone mineral density (BMD) and body mass index was found to be direct, and the one between BMD and the duration of the disease and the cumulative dose of glucocorticoids was found to be inverse. The blood vitamin D level (25(OH)D) was significantly lower in patients than in controls (19.3 ± 7.4 ng/ml and 23.3 ± 8.6 ng/ml, respectively), and among individuals with SSD it was significantly lower in patients with OP than in patients without OP (p &lt;0.05). 85% examined patients with SSD needed the anti-osteoporotic therapy. Treatment with the generic alendronate in the form of effervescent tablets to prepare Binosto buffer solution was effective and safe in patients with SSD with esophageal hypotension.

Cost-effectiveness of pulse-echo ultrasonometry in osteoporosis management.

PurposeOsteoporosis is asymptomatic morbidity of the elderly which develops slowly over several years. Osteoporosis diagnosis has typically involved Fracture Risk Assessment (FRAX) followed by dual energy X-ray absorptiometry (DXA) in specialist care. Point-of-care pulse-echo ultrasound (PEUS) was developed to overcome DXA-related access issues and to enable faster fracture prevention treatment (FPT) initiation. The objective of this study was to evaluate the cost-effectiveness of two proposed osteoporosis management (POMs: FRAX→PEUS-if-needed→DXA-if-needed→FPT-if-needed) pathways including PEUS compared with the current osteoporosis management (FRAX→DXA-if-needed→FPT-if-needed).Materials and methodsEvent-based probabilistic cost–utility model with 10-year duration for osteoporosis management was developed. The model consists of a decision tree for the screening, testing, and diagnosis phase and is followed by a Markov model for the estimation of incidence of four fracture types and mortality. Five clinically relevant patient cohorts (potential primary FPT in women aged 75 or 85 years, secondary FPT in women aged 65, 75, or 85 years) were modeled in the Finnish setting. Generic alendronate FPT was used for those diagnosed with osteoporosis, including persistence overtime. Discounted (3%/year) incremental cost-effectiveness ratio was the primary outcome. Discounted quality-adjusted life-years (QALYs), payer costs (year 2016 value) at per patient and population level, and cost-effectiveness acceptability frontiers were modeled as secondary outcomes.ResultsPOMs were cost-effective in all patient subgroups with noteworthy mean per patient cost savings of €121/76 (ranges €107–132/52–96) depending on the scope of PEUS result interpretation (test and diagnose/test only, respectively) and negligible differences in QALYs gained in comparison with current osteoporosis management. In the cost-effectiveness acceptability frontiers, POMs had 95%–100% probability of cost-effectiveness with willingness to pay €24,406/QALY gained. The results were robust in sensitivity analyses. Even when assuming a high cost of PEUS (up to €110/test), POMs were cost-effective in all cohorts.ConclusionThe inclusion of PEUS to osteoporosis management pathway was cost-effective.

Denosumab: A Unique Perspective on Adherence and Cost-effectiveness Compared With Oral Bisphosphonates in Osteoporosis Patients.

To assess the cost-effectiveness as well as adherence and patient preference for denosumab compared with oral bisphosphonates for the treatment of osteoporosis. Two comprehensive PubMed literature searches (from data inception to December 2017) were performed. The first search included the terms osteoporosis, denosumab, bisphosphonate, and adherence or persistence or compliance or preference. The search terms osteoporosis, denosumab, cost, and effectiveness were used in the second literature search. Additional references were included from reviewing literature citations. All English-language clinical trials on adherence (as compliance and persistence) or patient preference for denosumab compared with oral bisphosphonates were evaluated. In addition, articles analyzing the cost-effectiveness of denosumab compared with generic alendronate were evaluated. Four studies that assessed patient preference showed positive outcomes for preference and satisfaction for subcutaneous use of denosumab every 6 months versus oral alendronate weekly, oral ibandronate monthly, or oral risedronate monthly. Three studies evaluated persistence and compliance and/or adherence and showed improved persistence and compliance rates with denosumab compared with bisphosphonate therapy. Twelve articles and 3 abstracts assessed cost-effectiveness of denosumab compared with generic alendronate. The majority of articles showed that denosumab was cost-effective, and even cost-saving in patients older than 75 years of age and those who have a history of previous fractures, lower bone mineral density T-scores, and more risk factors. Denosumab compared with oral bisphosphonates may improve patient preference and adherence as well as provide a cost-effective treatment strategy, especially among higher-risk and older adults with osteoporosis.

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax&lt;sup&gt;&amp;reg;&lt;/sup&gt; tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

PurposeThe aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet.Materials and methodsA single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods.ResultsThe average maximum concentrations (Cmax) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR) for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were −0.16 and −0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%.ConclusionThe generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions.

What are we paying for? A cost-effectiveness analysis of patented denosumab and generic alendronate for postmenopausal osteoporotic women in Australia.

ObjectiveZoledronic acid and denosumab were funded by the Australian government for the management of osteoporosis at an equivalent price to alendronate. The price of alendronate has declined by around 65 %, but the price of the other two therapies has remained stable. Using data published since the listing, this paper reports current estimates of the value of denosumab compared to alendronate from an Australian health system perspective.MethodsA cohort-based state transition model was developed that predicted changes in bone mineral density (BMD), and calibrated fracture probabilities as a function of BMD, age and previous fracture to estimate differences in costs and QALYs gained over a 10-year time horizon.ResultsThe base-case incremental cost per QALY gained for denosumab versus alendronate was $246,749. There is a near zero probability that denosumab is cost-effective at a threshold value of $100,000 per QALY gained. If the price of denosumab was reduced by 50 %, the incremental cost per QALY gained falls to $50,068.DiscussionCurrent Australian legislation precludes price reviews when comparator therapies come off patent. The presented analysis illustrates a review process, incorporating clinical data collected since the original submission to inform a price at which denosumab would provide value for money.

Cost-Effectiveness of Intervention Thresholds for the Treatment of Osteoporosis Based on FRAX(®) in Portugal.

Cost-effective intervention thresholds (ITs) based on FRAX(®) were determined for Portugal. Assuming a willingness to pay (WTP) of €32,000 per quality-adjusted life years (QALYs), treatment with generic alendronate is cost effective for men and women aged 50years or more, with 10-year probabilities for major osteoporotic fractures and hip above 8.8 and 2.5%, respectively. The aim of the present study was to identify the 10-year probabilities of a major and hip osteoporotic fracture using FRAX(®) validated for Portugal, above which pharmacologic interventions become cost effective in the Portuguese context. A previously developed and validated state transition Markov cohort model was populated with epidemiologic, economic and quality-of-life fracture data from Portugal. Cost-effectiveness of FRAX(®)-based ITs was calculated for generic alendronate and proprietary zoledronic acid, denosumab and teriparatide were compared to "no intervention", assuming a WTP of €32,000 (two times national Gross Domestic Product per capita) per QALYs. In the Portuguese epidemiological and economic context, treatment with generic alendronate was cost effective for men and women aged 50years or more, with 10-year probabilities at or above 8.8% for major osteoporotic fractures and 2.5% for hip fractures. Cost-effective threshold 10-year probabilities for major osteoporotic and hip fractures were higher for zoledronic acid (20.4 and 10.1%), denosumab (34.9 and 10.1%) and teriparatide (77.8 and 62.6%), respectively. A tool is provided to perform the calculation of cost-effective ITs for different medications, according to age group and diverse levels of WTP. Cost-effective ITs, for different medications, age groups and WTP, based on 10-year probabilities of major and hip fracture probabilities calculated with FRAX are provided.

PMS84 - Comparative Effectiveness and Cost-Effectiveness of Generic Alendronate, Risendronate, Denosumab and Zolendronic Acid for Secondary Prevention of Fragility Fractures - Perliminay Results

PMS84 - Comparative Effectiveness and Cost-Effectiveness of Generic Alendronate, Risendronate, Denosumab and Zolendronic Acid for Secondary Prevention of Fragility Fractures - Perliminay Results

Denosumab for Elderly Men with Osteoporosis: A Cost-Effectiveness Analysis from the US Payer Perspective.

Purpose. To evaluate the cost-effectiveness of denosumab versus other osteoporotic treatments in older men with osteoporosis from a US payer perspective. Methods. A lifetime cohort Markov model previously developed for postmenopausal osteoporosis (PMO) was used. Men in the model were 78 years old, with a BMD T-score of −2.12 and a vertebral fracture prevalence of 23%. During each 6-month Markov cycle, patients could have experienced a hip, vertebral or nonhip, nonvertebral (NHNV) osteoporotic fracture, remained in a nonfracture state, remained in a postfracture state, or died. Background fracture risks, mortality rates, persistence rates, health utilities, and medical and drug costs were derived from published sources. Previous PMO studies were used for drug efficacy in reducing fracture risk. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, risedronate, ibandronate, teriparatide, and zoledronate. Results. Denosumab had an incremental cost-effectiveness ratio (ICER) of $16,888 compared to generic alendronate and dominated all other treatments. Results were most sensitive to changes in costs of denosumab and the relative risk of hip fracture. Conclusion. Despite a higher annual treatment cost compared to other medications, denosumab is cost-effective compared to other osteoporotic treatments in older osteoporotic US men.

Denosumab: A cost-effective alternative for older men with osteoporosis from a Swedish payer perspective

ObjectiveTo assess the cost-effectiveness of denosumab versus other treatments in men with osteoporosis who are ≥75years old from a payer perspective in Sweden. MethodsA 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. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Estimates of fracture efficacy were drawn from available studies in post-menopausal osteoporotic (PMO) women as BMD improvements have been shown to be similar across male osteoporosis (MOP) and PMO populations, and a recent clinical trial suggested that the fracture risk reduction from bisphosphonate therapy in men is similar to that seen in women in comparable studies. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, ibandronate, zoledronate, strontium ranelate and teriparatide. On average, patients in the model were 78years old, with bone mineral density T-score at the femoral neck of −2.12. Prevalent vertebral fractures were present in 23% of patients. In the base-case, the model assumed that patients would experience treatment-related effects up to 2years after discontinuation. Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. ResultsTotal lifetime costs for denosumab, alendronate, strontium ranelate, zoledronate, risedronate, ibandronate and teriparatide were €31,004, €33,731, €34,788, €34,796, €34,826, €35,983 and €37,461, respectively. Total QALYs were 5.23, 5.15, 5.15, 5.17, 5.13, 5.12 and 5.22, respectively. Compared to other treatments, denosumab had the lowest costs and highest QALYs. In the one-way sensitivity analyses, when compared to alendronate (next least expensive strategy), the ICER for denosumab was most sensitive to the relative risk of hip fracture on denosumab. The probability of denosumab being cost-effective compared to the other treatments at a threshold of €66,000/QALY was 96.1%. ConclusionDenosumab dominated all comparators, including generic bisphosphonates, in the treatment of osteoporosis in men who were ≥75years old in Sweden.

A critical review of brand and generic alendronate for the treatment of osteoporosis.

ObjectiveCompare in vitro and in vivo characteristics and clinical outcomes of brand and generic alendronate.Research design and methods: Relevant search terms were input into Medline ("alendronate" AND "generic" up to August 5, 2013) and any abstracts deemed possibly relevant selected for full paper review and abstraction.ResultsMulticentre, randomized, placebo-controlled Phase III clinical trials of substantial size and duration have established the anti-fracture efficacy and safety of brand amino-bisphosphonates. For regulatory approval, generic versions of brand drugs need to demonstrate bioequivalence in young, healthy volunteers and have similar dissolution times. While the potency and amount of active drug within generic formulations must be identical to the brand, differences are permitted in the excipients. Significant differences in tablet disintegration time among different versions of generic and brand alendronate have been reported. Rapidly disintegrating alendronate pills may increase oesophageal bioadhesion and adverse event risk. Oesophageal-bound alendronate or slow disintegrating alendronate tablets may be made inert and ineffective by subsequently ingested food or drink. Investigations have reported a lower persistence to therapy with generic brands of alendronate as compared to brand bisphosphonates and patients switched from brand to generic alendronate have increased adverse event rates and losses in bone mineral density.ConclusionNumerous differences exist between brand and generic alendronate including: disintegration time, bioadhesion to the oesophagus, patient persistence to therapy, adverse event incidence, and maintenance of bone mineral density. Generic forms of alendronate warrant closer clinical study before they are ascribed the clinical effectiveness and tolerability of brand alendronate.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-550) contains supplementary material, which is available to authorized users.

Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture

IntroductionAn increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate.MethodsIn a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models.ResultsThere were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95%CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p < 0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95%CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12.ConclusionsBone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent fracture.Trial RegistrationDutch Trial Register NTR number 1867 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1867

Cost Effectiveness of Denosumab versus Oral Bisphosphonates for Postmenopausal Osteoporosis in the US

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. The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. 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. 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. 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.

SAT0372 Comparing tolerability and efficacy of generic versus brand alendronate. A cross-over study in postmenopausal women with osteoporosis

BackgroundDuring recent years an increasing amount of generic alendronate formulations has become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate...

PMS30 - Is Denosumab Cost-Effective Compared To Oral Bisphosphonates For The Treatment Of Male Osteoporosis (Mop) In Sweden?

PMS30 IS DENOSUMAB COST-EFFECTIVE COMPARED TO ORAL BISPHOSPHONATES FOR THE TREATMENT OF MALE OSTEOPOROSIS (MOP) IN SWEDEN? Parthan A1, Kruse MM1, Agodoa I2, Tao CY1, Silverman SL3, Orwoll E4 1OptumInsight, Cambridge, MA, USA, 2Amgen Inc., Thousand Oaks, CA, USA, 3CedarsSinai Hospital, Beverly Hills, CA, USA, 4Oregon Health & Science University, Portland, OR, USA OBJECTIVES: Cost-effectiveness of denosumab versus oral bisphosphonates in MOP was evaluated from a third-party payer perspective in Sweden. METHODS: A lifetime cohort Markov model was developed to reflect osteoporotic health states. During each cycle, patients could have a fracture, remain healthy, remain in a post fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Bone mineral density (BMD) improvements have been shown to be similar between MOP and post-menopausal osteoporotic (PMO) populations, and a recent fracture trial showed zoledronate to have effects in men similar to those reported previously in women; therefore efficacy data from PMO women were used. Lifetime expected costs and quality-adjusted life-years (QALYs) were estimated for denosumab, generic alendronate, generic risedronate, and ibandronate. Patients in the model were 65-year-old men, with BMD T-score≤1.90 and prevalent vertebral fracture of 22.7%. In the base-case, the model assumed patients could receive treatment effects up to 2 years after discontinuation (offset time). Costs and QALYs were discounted at 3% annually. Extensive sensitivity analyses were conducted. RESULTS: Total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were €45,118, €45,396, €45,526, and €46,523, respectively. Total QALYs were 9.86, 9.91, 9.85, and 9.83, respectively. Denosumab had an incremental cost-effectiveness ratio (ICER) of €5,283 compared to alendronate and dominated risedronate and ibandronate. Results were most sensitive to changes in relative risk (RR) of hip fracture with denosumab, cost of denosumab and RR of vertebral fracture with denosumab. The probability of denosumab being cost-effective compared to oral bisphosphonates at a threshold of €66,000/QALY was 85.5%. In a sensitivity analysis of offset time of 5 years for oral bisphosphonates, denosumab had an ICER of €10,382 compared to alendronate. CONCLUSIONS: Denosumab is costeffective compared to branded and generic oral bisphosphonates in the Swedish MOP population.

Cost–effectiveness of denosumab in the treatment of postmenopausal osteoporotic women

Denosumab is a novel biological agent for the treatment of osteoporosis in postmenopausal women with increased risk of fractures. With limited healthcare resources, economic evaluations are increasingly being used by decision-makers to optimize healthcare resource allocation. The cost–effectiveness of denosumab has been evaluated in various studies, and a systematic literature study was conducted up to April 2012 to identify all published research articles and research abstracts presented at various congresses. This article provides a systematic review of four articles and eight abstracts reporting on the cost–effectiveness of denosumab in the treatment of osteoporosis. In most economic evaluations, denosumab has been considered as a cost-effective treatment compared with first-line and second-line options (including generic alendronate) in the treatment of women with high risk of fractures.

Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis

The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate. Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated. A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation. At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was-irrespective of age-cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20%. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32%, respectively. FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate.

Generic alendronate use among medicare beneficiaries: are part d data complete?

Generic alendronate was approved in the United States on February 6, 2008. Medicare beneficiaries might pay for generic alendronate out-of-pocket without having claims submitted, resulting in misclassification of generic alendronate use in Medicare data. To estimate the completeness of generic alendronate use in 2008 Medicare Part D data; to identify factors associated with staying on branded alendronate versus switching to a generic product. We identified Medicare beneficiaries highly adherent (medication possession ratio ≥80%) with branded alendronate during 1/1/06-2/6/07 ("2007 cohort") and during 1/1/07-2/6/08 ("2008 cohort"). The outcome was medication status at the end of follow-up (12/31/2007 or 12/31/2008), classified as continued branded alendronate, switched to generic alendronate, switched to another bisphosphonate or presumed discontinued bisphosphonate therapy. Cox regression estimated the hazard ratio (HR) for discontinuation in 2008 compared to 2007. Multinomial logistic regression identified factors associated with medication status for the 2008 cohort. Among 15,310 subjects using branded alendronate in the 2008 cohort, 81% switched to generic alendronate. The proportion presumably discontinuing bisphosphonate therapy was 8.9% in 2008 compared to 7.7% in the 2007 cohort (adjusted HR, 1.15; 95% confidence interval, 1.05, 1.26). Factors associated with staying on branded alendronate in 2008 were higher income, eligibility for a low income subsidy and use of Fosamax® plus vitamin D. Evaluation of Medicare prescription drug data suggests that the amount of missing claims for generic alendronate in 2008 was not substantial, and misclassification of exposure in studies examining alendronate use post-generic product availability should be minimal.