Denosumab Safety Assessment in Multiple Observational Databases
Study Details
Study Description
Brief Summary
This is a prospective open-cohort study with annual assessment and reporting of descriptive findings from 5 secondary data sources. The study period will include up to 10 years in each data system. The secondary data sources will be the following: US Medicare, including Parts A, B, and D United HealthCare* Scandinavian national health registry databases, including data from Denmark, Sweden, and Norway. Data will be collected for postmenopausal women overall, women with PMO, and patients who receive Prolia for unapproved indications.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Postmenopausal Women Postmenopausal Women |
|
| Women with post menopausal osteoporosis Women with post menopausal osteoporosis |
Drug: denosumab
subcutaneous injection
Drug: bisphosphonate
The assessment of bisphosphonates includes branded oral bisphosphonates (eg, alendronate [Fosamax®], risedronate [Actonel®], ibandronate [Boniva®/Bonviva®] oral); generic bisphosphonates, including alendronate, neridodronate, and olpadronate; intravenous bisphosphonates including ibandronate IV, and zoledronate [Reclast®/Aclasta®].
|
| Prolia for unapproved indications Patients who receive Prolia for unapproved indications |
Drug: denosumab
subcutaneous injection
|
| Men with osteoporosis Men with osteoporosis treated with denosumab |
Drug: denosumab
subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Incidence rates of Adverse Events of Special Interest (AESI) [10 years]
Incidence rates of AESI (per 100,000 Person-years) will be assessed by exposure cohort (denosumab or bisphosphonates (overall, oral or IV)).
- Characteristics and Adverse Events of Special Interest (AESI) risk factors [10 years]
Describe characteristics, clinical features, and AESI risk factors in women with PMO exposed to denosumab, women with PMO exposed to bisphosphonates, and all women with PMO.
- Compare the incidence of the Adverse Events of Special Interests [10 years]
Compare the incidence of the AESI in women with PMO exposed to denosumab to that in women with PMO exposed to bisphosphonates.
- Describe incidence rates of Adverse Events of Special Interest (AESI) [10 years]
Describe incidence rates of AESI in postmenopausal women.
- Describe denosumab utilization patterns [10 years]
Describe denosumab utilization patterns in patients who receive denosumab therapy for treatment of PMO.
- Describe Prolia utilization patterns [10 years]
Describe Prolia utilization patterns in patients who receive Prolia therapy for unapproved indications (indication, dosage, frequency).
Eligibility Criteria
Criteria
Inclusion Criteria for women with postmenopausal osteoporosis:
-
Postmenopausal women: Postmenopausal status will be determined based on age and defined as women ≥ 55 years old. For the Medicare database, only women ≥ 65 years old will be included in the analysis, given that generally all individuals in the US ≥ 65 years old are eligible for Medicare coverage and data on postmenopausal women less than 65 years old will be available for only a small number of women meeting other specialized eligibility criteria.
-
Women with Post Menopausal Osteoporosis: The presence of Post Menopausal Osteoporosis will be determined utilizing an algorithm based upon definition of postmenopausal women (≥ 65 years old in Medicare or ≥ 55 years old in other data systems), diagnostic codes indicating osteoporosis, diagnostic codes indicating osteoporotic fracture, and/or relevant postmenopausal osteoporosis treatment codes.
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The inclusion of men and women who have Glucocorticoid Induced Osteoporosis (GIOP) has also been added to the study population. Men and women who receive Prolia with glucocorticoid exposure are included in the ongoing study 20090522 to assess safety in the post-marketing environment
Exclusion Criteria for women with postmenopausal osteoporosis:
• Women with postmenopausal osteoporosis: Women with Paget's disease during the 12-month period prior to meeting criteria for inclusion in postmenopausal osteoporosis population will be excluded. Additionally, in US Medicare and United Healthcare, women with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12-months before index date will be excluded. In the Scandinavian national registries, women with a diagnosis of cancer according to the patient registry and/or cancer registry up to 12-months prior to meeting criteria for inclusion in postmenopausal osteoporosis population will be excluded.
Inclusion criteria for men with osteoporosis:
- Men ≥ 65 years old in the Medicare database or ≥ 30 years old in United Healthcare who receive at least one denosumab 60 mg injection will be included. All men need to be continuously enrolled for at least 12 months prior to start of follow-up. A diagnosis code of osteoporosis or osteoporotic fracture would not be required because it is known that male osteoporosis is under-diagnosed. The exclusion of patients with cancer or Paget disease (as described in the Exclusion Criteria Section) will ensure that patients treated with Prolia is for osteoporosis but not for other indications. The index date is defined as the date when a patient first satisfies all inclusion criteria.
Exclusion Criteria for men with osteporosis:
-
Men with a diagnosis of malignancy (excluding non-melanoma skin cancer) or treatment with chemotherapy, hormonal therapy or radiation therapy for cancer up to 12 months before the index date will be excluded.
-
Men with Paget's disease during the 12-month period prior to the index date will also be excluded.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
- Aarhus University Hospital
- Optum, Inc.
- University of Alabama at Birmingham
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 20090522