Osteoporosis, Postmenopausal
Conditions
Brief summary
The purpose of the study is to evaluate the real-world effectiveness and cardiovascular safety of ABL compared with TPTD during the 18-month period after treatment initiation in propensity score (PS)-matched cohorts
Detailed description
This is a retrospective observational cohort study using healthcare administrative claims data from the USA. This study will use anonymized patient claims data from PRA's Symphony Health Patient Source Integrated Dataverse (IDV) database including the enhanced hospital data. Data are routinely collected in healthcare encounters from all available healthcare sites (inpatient hospital, outpatient hospital, physician office, pharmacy, etc.) for all types of provided services including specialty, preventive care, and office-based treatments. The patients for inclusion in the study analyses will be identified based on the prescribed anabolic therapy filled (ABL or TPTD). The identification period (May 1, 2017 to June 30, 2019) was chosen to coincide with the date of the FDA approval of ABL in the USA.
Interventions
DRUGAbaloparatide
Abaloparatide subcutaneous (abaloparatide SC \[ABL\]; Tymlos®)
DRUGTeriparatide
Teriparatide subcutaneous (TPTD; Forteo®)
Sponsors
PRA Health Sciences
Radius Health, Inc.
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women who are 50 years or older * ≥1 prescription fill for ABL or TPTD during the identification period * ≥ 1 claim for medical or hospital visit and a pharmacy claim in the 12 months before the index date
Exclusion criteria
* Paget's disease * Malignancy, except for nonmelanoma skin cancers, carcinoma in-situ of the cervix, ductal carcinoma in-situ of breast * Indicators of high disease burden and high risk of death * With prior index anabolic treatment * Switch to a different anabolic treatment after index date
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Nonvertebral Fracture | From index date up to 19 months | A nonvertebral fracture is any fragility fracture at the hip, pelvis, femur, ankle, shoulder (including shoulder, humerus, clavicle), radius/ulna, wrist, or tibia/fibula. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. A claims-based algorithm with high specificity for fracture site was used to identify osteoporosis related fractures. Patients were followed for up to 18 months after their index date, plus 30 days follow-up or until their first nonvertebral fracture event or hospital death, whichever came first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Endpoint of Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or In-hospital Cardiovascular Death | From index date up to 19 months | Cardiovascular safety was evaluated based only on events occurring from the beginning of the index period through 19 months. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. Cardiovascular events (MI and stroke) were defined as the first post-index incidence recorded on a hospital claim or physician claim. A validated claims-based algorithm was used to identify deaths, based on hospital discharge status, that are likely to be caused by cardiovascular events. Patients were followed for up to 18 months while on treatment plus 30 days follow-up, or until their first cardiovascular event (MI or stroke) or hospital death, whichever came first. |
| Number of Participants With a Composite Endpoint of Nonfatal MI, Nonfatal Stroke, Heart Failure or In-hospital Cardiovascular Death | From index date up to 19 months | Cardiovascular safety was evaluated based only on events occurring from the beginning of the index period through 19 months. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. Cardiovascular events (MI, stroke, and heart failure) were defined as the first post-index incidence recorded on a hospital claim or physician claim. A validated claims-based algorithm was used to identify deaths, based on hospital discharge status, that are likely to be caused by cardiovascular events. Patients were followed for up to 18 months while on treatment plus 30 days follow-up, or until their first cardiovascular event (MI, stroke, or heart failure) or hospital death, whichever came first. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hip Fracture | From index date up to 19 months | The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. A claims-based algorithm with high specificity for fracture site was used to identify osteoporosis related fractures. Patients were followed up for 18 months after their index date, plus 30 days follow-up or until their first hip fracture event or hospital death, whichever came first. |
Countries
United States
Participant flow
Pre-assignment details
Propensity score (PS) matching was used to create treatment cohorts. Patients were matched using an extensive list of indicators of disease severity and fracture risk, including fracture and treatment history, as well as conditions associated with increased risk of fall and the requirement for treatments associated with poor bone health or quality.
Participants by arm
| Arm | Count |
|---|---|
| Patients Treated With ABL Patients who filled ≥ 1 prescription for ABL (TYMLOS) as their index medication during the identification period. | 11,027 |
| Patients Treated With TPTD Patients who filled ≥ 1 prescription for TPTD (Forteo) as their index medication during the identification period. | 11,027 |
| Total | 22,054 |
Baseline characteristics
| Characteristic | Patients Treated With TPTD | Total | Patients Treated With ABL |
|---|---|---|---|
| Age, Continuous | 67.4 years STANDARD_DEVIATION 8.39 | 67.38 years STANDARD_DEVIATION 8.37 | 67.3 years STANDARD_DEVIATION 8.35 |
| Race/Ethnicity, Customized African American | 150 Participants | 294 Participants | 144 Participants |
| Race/Ethnicity, Customized Asian | 104 Participants | 204 Participants | 100 Participants |
| Race/Ethnicity, Customized Hispanic | 531 Participants | 1177 Participants | 646 Participants |
| Race/Ethnicity, Customized Other | 107 Participants | 234 Participants | 127 Participants |
| Race/Ethnicity, Customized Unknown | 5873 Participants | 11746 Participants | 5873 Participants |
| Race/Ethnicity, Customized White | 4262 Participants | 8399 Participants | 4137 Participants |
| Sex: Female, Male Female | 11027 Participants | 22054 Participants | 11027 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 11,027 | 9 / 11,027 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Participants With a Nonvertebral Fracture
A nonvertebral fracture is any fragility fracture at the hip, pelvis, femur, ankle, shoulder (including shoulder, humerus, clavicle), radius/ulna, wrist, or tibia/fibula. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. A claims-based algorithm with high specificity for fracture site was used to identify osteoporosis related fractures. Patients were followed for up to 18 months after their index date, plus 30 days follow-up or until their first nonvertebral fracture event or hospital death, whichever came first.
Time frame: From index date up to 19 months
Population: All patients meeting the study inclusion/exclusion criteria and selected after PS-matching.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Treated With ABL | Number of Participants With a Nonvertebral Fracture | 313 Participants |
| Patients Treated With TPTD | Number of Participants With a Nonvertebral Fracture | 333 Participants |
95% CI: [0.81, 1.1]
Secondary
Number of Participants With a Composite Endpoint of Nonfatal MI, Nonfatal Stroke, Heart Failure or In-hospital Cardiovascular Death
Cardiovascular safety was evaluated based only on events occurring from the beginning of the index period through 19 months. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. Cardiovascular events (MI, stroke, and heart failure) were defined as the first post-index incidence recorded on a hospital claim or physician claim. A validated claims-based algorithm was used to identify deaths, based on hospital discharge status, that are likely to be caused by cardiovascular events. Patients were followed for up to 18 months while on treatment plus 30 days follow-up, or until their first cardiovascular event (MI, stroke, or heart failure) or hospital death, whichever came first.
Time frame: From index date up to 19 months
Population: All patients meeting the study inclusion/exclusion criteria and selected after PS-matching.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Treated With ABL | Number of Participants With a Composite Endpoint of Nonfatal MI, Nonfatal Stroke, Heart Failure or In-hospital Cardiovascular Death | 495 Participants |
| Patients Treated With TPTD | Number of Participants With a Composite Endpoint of Nonfatal MI, Nonfatal Stroke, Heart Failure or In-hospital Cardiovascular Death | 471 Participants |
Comparison: Cox proportional hazard model was used to calculate the hazard ratio with teriparatide as reference. Noninferiority of abaloparatide to teriparatide was to be concluded if the upper bound of the 2-sided 95% CI of the HR between abaloparatide versus teriparatide was \<1.3.95% CI: [0.95, 1.22]
Secondary
Number of Participants With Composite Endpoint of Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or In-hospital Cardiovascular Death
Cardiovascular safety was evaluated based only on events occurring from the beginning of the index period through 19 months. The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. Cardiovascular events (MI and stroke) were defined as the first post-index incidence recorded on a hospital claim or physician claim. A validated claims-based algorithm was used to identify deaths, based on hospital discharge status, that are likely to be caused by cardiovascular events. Patients were followed for up to 18 months while on treatment plus 30 days follow-up, or until their first cardiovascular event (MI or stroke) or hospital death, whichever came first.
Time frame: From index date up to 19 months
Population: All patients meeting the study inclusion/exclusion criteria and selected after PS-matching.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Treated With ABL | Number of Participants With Composite Endpoint of Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or In-hospital Cardiovascular Death | 221 Participants |
| Patients Treated With TPTD | Number of Participants With Composite Endpoint of Nonfatal Myocardial Infarction (MI), Nonfatal Stroke, or In-hospital Cardiovascular Death | 211 Participants |
Comparison: Cox proportional hazard model was used to calculate the hazard ratio with teriparatide as reference. Noninferiority of abaloparatide to teriparatide was to be concluded if the upper bound of the 2-sided 95% CI of the HR between abaloparatide versus teriparatide was \<1.3.95% CI: [0.89, 1.3]
Other Pre-specified
Number of Participants With Hip Fracture
The date of the first prescription claim for either abaloparatide or teriparatide during the identification period was considered the index date. A claims-based algorithm with high specificity for fracture site was used to identify osteoporosis related fractures. Patients were followed up for 18 months after their index date, plus 30 days follow-up or until their first hip fracture event or hospital death, whichever came first.
Time frame: From index date up to 19 months
Population: All patients meeting the study inclusion/exclusion criteria and selected after PS-matching.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients Treated With ABL | Number of Participants With Hip Fracture | 112 Participants |
| Patients Treated With TPTD | Number of Participants With Hip Fracture | 125 Participants |