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ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 Oyágüez Martín I1, Gómez Alonso C2, Marqués de Torres M3, García Coscolín T4, Betegón Nicolás L4, Casado Gómez MA1
1 Pharmacoeconomics & Outcomes Research Iberia - Madrid
2 Servicio de Metabolismo Óseo y Mineral - HUCA - Oviedo
3 Farmaceútico de Atención Primaria - Area Sanitaria Este de Málaga-Axarquia
4 Departamento Economía de la Salud - Sanofi-Aventis - Madrid
Evaluation of the risedronate efficiency
75 mgs versus generic alendronate 70
mgs, in women with post-menopausal
osteoporosis and previous vertebral
fractures in Spain

Correspondence: Itziar Oyágüez - Pharmacoeconomics & Outcomes Research Iberia - Segundo Mata, 1 -28224 Pozuelo de Alarcón - Madrid (Spain)e-mail: Summary
Introduction: The objective is to assess the cost-effectiveness of risedronate 75 mg 2 consecutive
days/month vs generic alendronate 70 mg weekly, during one year in 75 years old females with post-
menopausal osteoporosis and previous vertebral fracture.
Methods: A cost-effectiveness analysis under Health National System perspective has been developed to
assess clinical (hip fracture prevention and quality adjusted life years gained) and economic conse-
quences (€ 2010) during 5 years following one year treatment with both alternatives. Drug effect has
been considered during the one year of drug administration. Epidemiology data and unitary costs were
derived from Spanish literature.
Results: In a cohort of 1.000 females, (75 years old) with post-menopausal osteoporosis and vertebral frac-
tures, risedronate 75 mg vs alendronate avoid 10 hip fractures, with 9.983€/hip fracture avoided cost.
Aditional QALY gained are 4 with an incremental cost of 99,83€. Incremental cost-effectiveness ratio
(ICER) is 24.957€ per QALY gained with risedronate 75 mg vs generic alendronate 70 mg.
Conclusion: In the treatment of females with post-menopausal osteoporosis and previous vertebral frac-
ture, risedronate 75 mg 2 consecutive days/month compared to generic alendronate 70 mg weekly is an
efficient strategy in Spain.
Key words: Osteroporosis, Risedronate, Alendronate, Costs.
ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 Introduction
this case, the data on effectiveness are obtained Osteoporosis constitutes a significant public health from a sub-analysis of the REAL (the RisedronatE problem, with a great clinical and economic and ALendronate study) study17. The REAL study18, impact1. In Spain, 25% of women aged between 60 is a retrospective observational cohort study in and 69 years, and 40% between 70 and 79 years, which are compared the effectiveness of weekly administration of alendronate with risedronate in A Spanish study carried out locally, found that the reduction of vertebral and hip fractures. The the prevalence of vertebral fracture in people over effectiveness of generic alendronate included in 50 years varies between 17.4 and 24.6% depending the economic evaluation was considered to be on the radiological criteria used, this prevalence equivalent to the original alendronate which was increasing with age. In fact the number of fractures practically doubles for each 10 years of age3.
Within osteoporotic fractures, hip fractures are Economic analysis
those with the strongest direct link to osteoporosis, The calculation of the efficiency comparison bet- due to their serious clinical consequences, their ween risedronate and alendronate was carried out higher requirement for days of rehabilitation and by means of the ICER19 relationship between the costs of hospitalisation4,5. It is estimated that there two alternatives using the following formula: are, globally, 1.6 million hip fractures annually,which could reach 4.5 million in the year 20505,6.
COST OF RISEDRONATE – COST Of ALENDRONATE The biphosphonates are considered to be the ICER = ----------------------------------------------------------------------------------------- medicines of first choice in the treatment and pre- EFECTIVENESS OF RISEDRONATE – EFECTIVENESS OF ALENDRONATE vention of osteoporotic fractures7, but a significantpercentage of women with osteoporosis disconti- The costs of each of the therapies include the nue treatment, or do not adhere to it8, due to the total costs of treatment and of fractures.
dosage, frequency of administration and the occu- To measure the effectiveness, the number of hip rrence of adverse events. The discontinuation and fractures avoided (using the incidence of fractures lack of adherence to treatment are associated with according to age and the efficacy of each medici- an increase in the risk of fractures9-11 and in health ne), and life years for quality adjusted life years costs12. The relationship between the cost of treat- (QALY) gained by each alternative, was used.
ments for osteoporosis and the results obtained by To determine whether the adoption of an alter- their use (number of fractures avoided and survi- native has a reasonable increased cost in relation val in quality adjusted life years) is a relevant fac- to the increase in effectiveness achieved, in the tor in taking decisions in clinical practice13.
cost-utility analysis the maximum efficiency or The aim of this evaluation has been to estima- cost threshold was defined as that cost which it te, from the health perspective, the Incremental was prepared to be paid for each additional unit cost-effectiveness ratio (ICER) relationship betwe- of effectiveness achieved with one therapeutic en the biphosphonates 75 mg risedronate for 2 option compared with another. In this study the consecutive days/month and 70 mg generic alen- efficiency threshold was considered to be 38,000€ dronate weekly, administered for a year, in per quality adjusted life year. This value was obtai- women over 75 years of age with OPM and PVF.
ned by updating to the year 2010, using the gene-ral consumer price index20, the normally accepted threshold value for economic evaluation in Spain, Patients
(30,000€ per year of life gained in the year 2000)21, The profile of the population analysed in this eco- and which agrees with the recommendations for nomic evaluation is: women of 75 years of age, Spain of other authors which place the threshold with a bone mineral density of ≤ -2.5 SD (T-score in a range between 30,000 and 45,000€ for each quality adjusted life year gained22. In addition, a The case base of the analysis centres on a hypo- threshold has recently been established in a series thetical cohort of 1,000 patients, although a sensi- of countries, among which Spain is included, for tivity analysis was also carried out which showed health interventions indicated for the treatment of the results applied to the female Spanish popula- osteoporosis23. This threshold, specific for the tion from 65 to 8014, to which was applied the rate interpretation of results in osteoporosis in Spain, of osteoporosis15, which were weighted into 8 dif- has been positioned at 47,000US$, equivalent to ferent strata due to the presence or not of PVF16.
34,768€, (using an exchange rate of 1 euro =1.3518 US$, at 15th May 2009; ECB)24.
Compared treatments
The alternative therapies compared were: 75 mg
risedronate for 2 days consecutively/month for a The economic analysis of risedronate compared year, against 70 mg generic alendronate weekly with alendronate was carried out using Markov’s model, which had allowed the estimation of thelong term (5 year) clinical and economic conse- Effectiveness of the medicines
quences of the administration of the two treat- The evaluation of the efficiency of medicines ments compared with a hypothetical cohort of requires the estimation of their effectiveness. In ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 The Markov models are characterised by their Estimation of costs
requirement for the definition of different states of All the costs included in the analysis are given in heath between which the patients may move. The euros (€, at 2010 value). The evaluation was model used in this study includes 4 different carried out from the perspective of the Spanish National Health System, which means that only -Healthy (not having suffered any hip fractures).
the direct health costs associated with the thera- -Post-fracture of the hip (first or second).
The pharmacological cost was calculated from -Death (whether due to hip fracture, or for the retail cost plus VAT of the medicines, for gene- ric alendronate, taking into account the stipulations Figure 1 shows a schematic representation of of the Law of Royal Decree 4/201025. The cost of hip fractures was obtained from the literature26.
Among the premises contained in the model, Table 1 includes the values of the relevant notable is the fact that discontinuations in treatment parameters and the unit costs used in the analysis.
have not been taken into account, which means that In agreement with current recommendations27 a the pharmacological cost of the therapy evaluated discount rate of 3% has been applied to the costs refers to the pharmacological cost of a complete year of treatment for each patient. In addition, anyresidual effects of the drugs have not been conside- Sensitivity analysis
red, rather, it has been assumed that the medicines The sensitivity analysis to confirm the stability of only had an effect during the year of administration. ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 -Obtained results for the Spanish female popu- tive days/month is more effective than therapy with lation of between 65 and 80 years of age (from 8 70 mg generic alendronate weekly, since more hip different strata), with OPM, weighted with/without fractures are avoided and the patient benefits from a PVF, and taking into account mortality due to hip greater number of quality adjusted life years.
The efficiency of the treatments for osteoporosis, -Considered the residual efficacy during the that is to say, the relationship between their cost and year following the end of the year of treatment.
the health benefits resulting from their use (reductionin risk and number of fractures avoided, and survival in quality adjusted life years), should be a key factor The administration of 75 mg risedronate for 2 conse- in taking decisions in normal clinical practice.
cutive days/month for a year in a cohort of 1,000 In comparison with 70 mg generic alendronate women of 75 years of age with OPM and PVF avoi- weekly, 75 mg risedronate for 2 consecutive ded 10 more hip fractures than the administration of days/month, is an efficient therapy (cost-effective 70 mg generic alendronate weekly for a year.
alternative). The study was based on an efficiency The cost of each additional hip fracture avoided threshold of 38,000 euros per quality adjusted life with 75 mg risedronate vs alendronate is 9,983€. year gained, derived by updating threshold of In the cohort of 1,000 women 2,919 QALYs were Sacristan et al. in values for 2009, of 38,220 euros21, achieved with 75 mg risedronate, compared with and the average of the threshold range established 2,915 with alendronate, which means an additional by De Cock et al., of 37,500 euros22. These values gain of 4 QALYs with the risedronate therapy, with a are close to the threshold determined for Spain in total increased cost of 99.83€ . The cost for each gain the treatment of osteoporosis of 34,768 euros22. The in QALY with risedronate as against alendronate is authors of this international study recommend the use of this threshold in the pharmacotherapeutic The results in the Spanish population females of guides, in combination with algorithms for the pre- between 65 and 80 years of age with OPM, aggre- diction of risk of fractures, to be used in taking deci- gated and weighted as a function of 8 different stra- sions with the aim of carrying out an efficient selec- ta, with or without PVF, show that the increase in tion of patients suitable for treatment. The efficiency cost per QALY gained with 75 mg risedronate for 2 threshold varied between the different countries as consecutive days/months is cost-effective in com- a function of the availability of funding for each parison with 70 mg generic alendronate weekly, quality adjusted life year, the costs associated with fractures and the costs of health interventions used The cost/additional QALY of risedronate, as against alendronate, is 13,374€/QALY in the popu- The results, aggregated and weighted in 8 stra- lation with PVF and 41.481€/QALY in the popula- ta representative of women of between 65 and 80 years of age according to the rate of osteoporosis When the residual effect of the therapies after and the incidence of PVF in Spain, confirmed the the end of the year of treatment is taken into con- robustness and consistency of the results.
sideration, the cost per hip fracture avoided with When the residual effects of the therapies at 75 mg risedronate for 2 consecutive days/month the end of the year of treatment are taken into as against 70 mg generic alendronate weekly is consideration, the cost-utility of 75 mg risedronate vs alendronate is only 8,065€/QALY and continues 8,065€/QALY with risedronate vs alendronate.
to be below the accepted efficiency threshold.
The results in the Spanish population between 65 This analysis considers treatments of a comple- and 80 years of age, weighted as a function of 8 dif- te year for each of the therapies. Adherence, with ferent strata, with or without PVF, taking into conside- its two facets: compliance and persistence, is a key ration the existence of residual efficacy, estimate that factor for being able to extrapolate the efficacy of the cost/additional hip fracture avoided is 12,241€ the biphosphonates demonstrated in the clinical and the cost/QALY is 25,488€/additional QALY with trials into clinical practice33,34, since the inadequate 75 mg risedronate vs generic alendronate.
adherence to treatment has been associated with Table 3 shows the detailed results of all the increase of 17% in the risk of fracture 10 and even 37% in the risk of hospitalisation for any cause35.
In addition to deteriorations in the state of health, Discussion
poor compliance and low persistence are also asso- Osteoporosis, in recent years, has consolidated its ciated with a reduction in the efficiency of the thera- position as one of the major socio-health problems in pies36. Adequate compliance, with rates from 50% Spain, both due to its high prevalence and for the and mainly of 75%37, are directly related to changes in bone mineral density in those patients, which as an Various studies have provided evidence that the- important marker for bone turnover, is considered a rapy with risedronate reduces the risk of fracture in good predictor for the reduction in risk of fractures.
women with osteoporosis29-32, even in the first 6 Adherence is therefore a challenge for clinicians months of treatment, giving it an added advantage involved in the treatment of osteoporosis32. Those medicines with the simplest and most time-spaced In women over 75 years of age with OPM and dosage regimens are better accepted by patients, PVF therapy with 75 mg risedronate for two consecu- ensuring greater compliance with the therapies38,39.
ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 Table 1. Principal variables of case base of model Parameter
Epidemiological data
Incidence of hip fractures (expressed per 10,000 inhabitants) Mortality in year following a hip fracture Effectiveness (reduction in hip fractures)
Cost data
75 mg risedronate – retail cost, plus VAT/day 70 mg alendronate – retail cost, plus VAT/day ORIGINAL ARTICLES / Rev Osteoporos Metab Miner 2011 3;1:21-29 Table 2. Results of the cost/utility analysis in the case base (women older than 75 years of age with postme-nopausal osteoporosis and previous vertebral fracture) Risedronate
vs Alendronate
The premise of total adherence to treatment As limitations and possible bias in this econo- adopted in the current analysis makes a conserva- mic evaluation, should be mentioned the inherent tive assumption for risedronate, since its monthly theoretical nature of any type of modelling which, administration has demonstrated significant impro- on occasions, does not give results which reflect vements with respect to the weekly administration of alendronate in adherence to treatment with The validity of an economic model is conditio- biphosphonates in women with OPM, with a com- nal on the quality of the data on which it is based.
pliance of 74% with monthly risedronate, as oppo- In our case, the principal source of information sed to 66% with weekly therapy with alendronate40. was the REAL study, a retrospective observational The consideration of a higher adherence to rise- study with a level of data lower than that of a cli- dronate therapy would not have been able to have nical trial, due to the possible existence of diffe- been extrapolated from the effectiveness data from rences in the characteristics of the cohorts which the REAL study18, which excluded the same propor- are compared. However, the use of data from ran- tion (41%) of patients in both treatment groups for domised clinical trials is also arguable, due to the not complying with the minimum period for adhe- rigidity of the inclusion criteria which do not make rence established in the trial’s protocols (3 months).
them representative of normal clinical practice, The efficiency of 35 mg risedronate as opposed principally when data from multinational studies to 70 mg of generic alendronate, both administered are used in economic evaluations at a local level46. weekly, has previously been established in the In conclusion, our results demonstrate the effi- Spanish environment41. Possible methodological ciency of therapy with 75 mg risedronate for 2 differences, as well as the reference years for the consecutive days/monthly compared with 70 mg costs, and differences in medical practice are a generic alendronate weekly in the treatment of barrier to direct comparisons with estimates of effi- women over 75 years of age with OPM in Spain.
ciency obtained in other countries. Even so, illus-tratively, it has been found that monthly therapywith risedronate is considered to be cost-effective Bibliography
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