Postmenopausal Osteoporosis
Conditions
Brief summary
The main objective of this observational study was to describe medication-taking behavior of patients treated with denosumab for postmenopausal osteoporosis (PMO) at 12 and 24 months.
Detailed description
The decision to treat patients with denosumab was made independent of and before their enrolment in the study. No study drug was administered as part of the study.
Interventions
None listed
Sponsors
Amgen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Indicated for treatment of osteoporosis in postmenopausal women at increased risk of fractures according to the approved Regional Prescribing Information (eg, EU SmPC in Germany, Austria, Greece and Belgium). * Enrolled into the study within 4 weeks of receiving their first injection of Prolia® according to the approved Regional Prescribing Information (eg, EU SmPC in Germany, Austria, Greece and Belgium). * Appropriate written informed consent has been obtained (as required per local country regulations).
Exclusion criteria
* Patient is currently enrolled in or has been enrolled within the prior 6 months in a study involving any investigational procedure, device or drug. * Contraindicated for treatment with Prolia® according to the approved Regional Prescribing Information (eg, EU SmPC in Germany, Austria, Greece and Belgium). * Participation in ongoing or previous denosumab clinical trials. * Patient has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the patient to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 12 months and 24 months | A participant was considered persistent with denosumab at 12 months if they received at least 1 denosumab injection following the pre-enrolment denosumab injection no later than 6 months + 8 weeks (ie, no greater than 239 days apart). A participant was considered persistent with denosumab at 24 months if they received at least 3 denosumab injections following the pre-enrolment denosumab injection, and the length of time between any 2 consecutive denosumab injections did not exceed 6 months + 8 weeks (ie, no greater than 239 days apart). |
| Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 12 months and 24 months | A participant was considered adherent to denosumab at 12 months if they received at least 1 denosumab injection over the 12-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart). A participant was considered adherent to denosumab at 24 months if they received at least 3 denosumab injections over the 24-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart). |
| Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | From baseline to 12 months and 24 months | MCR at 12 months was defined as the accumulative number of days covered with denosumab treatment during the first 12 months divided by 366 days, expressed as a percentage. MCR at 24 months was defined as the accumulative number of days covered with denosumab treatment during the first 24 months divided by 732 days, expressed as a percentage. It was assumed that each injection of denosumab treatment provided 6 months of coverage (or 183 days) from the date of injection or until the date of the next injection, whichever comes first. So, a participant who received only 1 injection in the first year would have MCR at 12 months equal to 50%. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months | Baseline and Month 24 | Bone mineral density was measured using dual energy X-ray absorptiometry (DXA). |
| Time to Non-persistence With Denosumab Injection | 24 months | Time to non-persistence for non-persistent patients was calculated as the time between the date of the first denosumab injection and the date of last denosumab injection received during the period where the patient was still classified as persistent, plus 6 months (183 days). Participants were considered persistent at 24 months if they received at least 4 injections, including the baseline injection, with no more than 6 months + 8 weeks apart between any 2 consecutive injections. |
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months | Baseline and Month 24 | Bone mineral density was measured using dual energy X-ray absorptiometry (DXA). |
| Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 24 months | The percentage of participants who received 0, 1, 2, or 3 denosumab injections within the specified window (defined by the persistence definition as 6 months + 8 weeks). The number of injections that a participant took during the 2-year period after the first pre-enrolment injection, and that were given within the appropriate window from the previous injection, irrespective of when the previous injection was given. Only the first 3 post-baseline injections are considered. |
| Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months | Baseline and Month 24 | Bone mineral density was measured using dual energy X-ray absorptiometry (DXA). |
Countries
Austria, Belgium, Germany, Greece
Participant flow
Recruitment details
The study was conducted at various study centers in Germany, Austria, Greece, and Belgium. The recruitment period was from 28 November 2012 to 31 August 2013.
Participants by arm
| Arm | Count |
|---|---|
| Germany Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice. | 579 |
| Austria Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice. | 300 |
| Greece Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice. | 299 |
| Belgium Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice. | 301 |
| Total | 1,479 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 12 | 3 | 2 | 11 |
| Overall Study | Full Consent/Agreement Withdrawn | 54 | 8 | 11 | 4 |
| Overall Study | Lost to Follow-up | 29 | 37 | 15 | 5 |
| Overall Study | Other | 44 | 10 | 7 | 15 |
Baseline characteristics
| Characteristic | Germany | Austria | Greece | Belgium | Total |
|---|---|---|---|---|---|
| Age, Continuous | 72.5 years STANDARD_DEVIATION 8.7 | 71.0 years STANDARD_DEVIATION 9.5 | 66.3 years STANDARD_DEVIATION 9.2 | 71.2 years STANDARD_DEVIATION 10.4 | 70.7 years STANDARD_DEVIATION 9.6 |
| Sex: Female, Male Female | 579 Participants | 300 Participants | 299 Participants | 301 Participants | 1479 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 579 | 0 / 300 | 0 / 300 | 0 / 301 |
| serious Total, serious adverse events | 2 / 579 | 0 / 300 | 0 / 300 | 1 / 301 |
Outcome results
Primary
Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months
MCR at 12 months was defined as the accumulative number of days covered with denosumab treatment during the first 12 months divided by 366 days, expressed as a percentage. MCR at 24 months was defined as the accumulative number of days covered with denosumab treatment during the first 24 months divided by 732 days, expressed as a percentage. It was assumed that each injection of denosumab treatment provided 6 months of coverage (or 183 days) from the date of injection or until the date of the next injection, whichever comes first. So, a participant who received only 1 injection in the first year would have MCR at 12 months equal to 50%.
Time frame: From baseline to 12 months and 24 months
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Germany | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 12 Months | 94.5 percentage of days of coverage |
| Germany | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 24 Months | 87.4 percentage of days of coverage |
| Austria | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 24 Months | 87.9 percentage of days of coverage |
| Austria | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 12 Months | 93.2 percentage of days of coverage |
| Greece | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 12 Months | 95.8 percentage of days of coverage |
| Greece | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 24 Months | 91.2 percentage of days of coverage |
| Belgium | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 12 Months | 96.2 percentage of days of coverage |
| Belgium | Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months | 24 Months | 92.4 percentage of days of coverage |
Primary
Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months
A participant was considered adherent to denosumab at 12 months if they received at least 1 denosumab injection over the 12-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart). A participant was considered adherent to denosumab at 24 months if they received at least 3 denosumab injections over the 24-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart).
Time frame: 12 months and 24 months
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Germany | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 12 Months | 87.6 percentage of participants |
| Germany | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 24 Months | 62.9 percentage of participants |
| Austria | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 24 Months | 66.0 percentage of participants |
| Austria | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 12 Months | 85.0 percentage of participants |
| Greece | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 12 Months | 89.6 percentage of participants |
| Greece | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 24 Months | 69.6 percentage of participants |
| Belgium | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 12 Months | 89.0 percentage of participants |
| Belgium | Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months | 24 Months | 70.1 percentage of participants |
Primary
Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months
A participant was considered persistent with denosumab at 12 months if they received at least 1 denosumab injection following the pre-enrolment denosumab injection no later than 6 months + 8 weeks (ie, no greater than 239 days apart). A participant was considered persistent with denosumab at 24 months if they received at least 3 denosumab injections following the pre-enrolment denosumab injection, and the length of time between any 2 consecutive denosumab injections did not exceed 6 months + 8 weeks (ie, no greater than 239 days apart).
Time frame: 12 months and 24 months
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Germany | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 12 Months | 92.2 percentage of participants |
| Germany | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 24 Months | 75.1 percentage of participants |
| Austria | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 24 Months | 79.7 percentage of participants |
| Austria | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 12 Months | 89.3 percentage of participants |
| Greece | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 12 Months | 94.3 percentage of participants |
| Greece | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 24 Months | 82.6 percentage of participants |
| Belgium | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 12 Months | 95.7 percentage of participants |
| Belgium | Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months | 24 Months | 86.0 percentage of participants |
Secondary
Percentage of Participants Who Received Denosumab Injections Within the Specified Window
The percentage of participants who received 0, 1, 2, or 3 denosumab injections within the specified window (defined by the persistence definition as 6 months + 8 weeks). The number of injections that a participant took during the 2-year period after the first pre-enrolment injection, and that were given within the appropriate window from the previous injection, irrespective of when the previous injection was given. Only the first 3 post-baseline injections are considered.
Time frame: 24 months
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Germany | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | No post-baseline injections | 5.9 percentage of participants | 0.9 |
| Germany | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 1 post-baseline injection | 7.8 percentage of participants | — |
| Germany | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 2 post-baseline injections | 11.2 percentage of participants | — |
| Germany | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 3 post-baseline injections | 75.1 percentage of participants | — |
| Austria | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 1 post-baseline injection | 3.7 percentage of participants | — |
| Austria | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 2 post-baseline injections | 7.0 percentage of participants | — |
| Austria | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 3 post-baseline injections | 79.7 percentage of participants | — |
| Austria | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | No post-baseline injections | 9.7 percentage of participants | 0.9 |
| Greece | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 2 post-baseline injections | 7.7 percentage of participants | — |
| Greece | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 1 post-baseline injection | 7.0 percentage of participants | — |
| Greece | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 3 post-baseline injections | 82.6 percentage of participants | — |
| Greece | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | No post-baseline injections | 2.7 percentage of participants | 0.7 |
| Belgium | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 3 post-baseline injections | 86.0 percentage of participants | — |
| Belgium | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 1 post-baseline injection | 3.0 percentage of participants | — |
| Belgium | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | No post-baseline injections | 3.7 percentage of participants | 0.7 |
| Belgium | Percentage of Participants Who Received Denosumab Injections Within the Specified Window | 2 post-baseline injections | 7.3 percentage of participants | — |
Secondary
Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months
Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).
Time frame: Baseline and Month 24
Population: Full analysis set with a baseline value and a month 24 value measured with the same body side and machine type.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Germany | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months | 3.4 percent change | Standard Deviation 5.4 |
| Austria | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months | 3.7 percent change | Standard Deviation 5.7 |
| Greece | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months | 6.0 percent change | Standard Deviation 9.5 |
| Belgium | Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months | 3.1 percent change | Standard Deviation 9.3 |
Secondary
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months
Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).
Time frame: Baseline and Month 24
Population: Full analysis set with a baseline value and a month 24 value measured with the same machine type.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Germany | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months | 6.5 percent change | Standard Deviation 6.2 |
| Austria | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months | 8.2 percent change | Standard Deviation 4.6 |
| Greece | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months | 8.4 percent change | Standard Deviation 8.3 |
| Belgium | Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months | 7.8 percent change | Standard Deviation 5.9 |
Secondary
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months
Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).
Time frame: Baseline and Month 24
Population: Full analysis set with a baseline value and a month 24 value measured with the same machine type.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Germany | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months | 4.4 percent change | Standard Deviation 6.2 |
| Austria | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months | 4.1 percent change | Standard Deviation 3.2 |
| Greece | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months | 6.6 percent change | Standard Deviation 6.6 |
| Belgium | Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months | 4.1 percent change | Standard Deviation 6.3 |
Secondary
Time to Non-persistence With Denosumab Injection
Time to non-persistence for non-persistent patients was calculated as the time between the date of the first denosumab injection and the date of last denosumab injection received during the period where the patient was still classified as persistent, plus 6 months (183 days). Participants were considered persistent at 24 months if they received at least 4 injections, including the baseline injection, with no more than 6 months + 8 weeks apart between any 2 consecutive injections.
Time frame: 24 months
Population: Full analysis set who were non-persistent at 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Germany | Time to Non-persistence With Denosumab Injection | 12.23 months |
| Austria | Time to Non-persistence With Denosumab Injection | 6.03 months |
| Greece | Time to Non-persistence With Denosumab Injection | 12.00 months |
| Belgium | Time to Non-persistence With Denosumab Injection | 12.20 months |