Study type

Study topic

Human medicinal product
Disease /health condition

Study type

Non-interventional study

Scope of the study

Assessment of risk minimisation measure implementation or effectiveness

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Anatomical Therapeutic Chemical (ATC) code

(M05BX04) denosumab
denosumab

Medical condition to be studied

Osteoporosis
Myocardial infarction
Ischaemic stroke
Haemorrhagic stroke
Population studied

Short description of the study population

Patients with osteoporosis satisfying the following eligibility criteria were included in the study:

Inclusion Criteria
Subjects will be included in the study population if they meet the following criteria:
1. Receipt of one or more administrations (ie, claim containing national drug code (NDC) or Healthcare Common Procedure Coding System (HCPCS) code) for denosumab or zoledronic acid between 01 October 2010 and 31 December 2017.
2. The index date is defined as the first date of administration of study medication (ie, denosumab or zoledronic acid) observable in the data between 01 October 2010 and 31 December 2017.
3. Subjects must be women or men age 55 years or older at index date.
4. At least 455 days of continuous enrollment preceding index date. A 455-day enrollment is included because the dosing interval for zoledronic acid is once a
year (365 days). Assessing 455 days (ie, 15 months) of look-back period will permit identification of past use.

Exclusion Criteria
Subjects will be excluded from the study if they meet any of the following criteria during the 455 days preceding the index date (ie, the baseline period)
1. Subjects with any of the following will be excluded to assure that denosumab is given for the osteoporosis indication
- Diagnosis of Paget’s disease of bone
- Diagnosis of cancer (excluding non-melanoma skin cancer)
- Treatment with chemotherapy,
- Treatment with hormonal therapy for cancer,
- Treatment with radiation or radiation therapy for cancer
2. To identify incident events, subjects with a history of stroke or MI events during the 455-day baseline period will be excluded.
3. Previous administration for denosumab or zoledronic acid prior to the index date. Look-back will include all available data (with a minimum required look-back
period of 455 days prior to index date).
- For this exclusion, denosumab use prior to 01 October 2010 will be identified by nonspecific codes (CPT codes: J3490and J3590) in combination with ICD-9 diagnostic codes for osteoporosis prior to 01 October 2010.

Age groups

Adults (46 to < 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

120000
Study design details

Main study objective

Among postmenopausal women and men with osteoporosis, evaluate the risk of cerebrovascular and cardiovascular events in subjects initiating treatment with denosumab relative to those initiating treatment with zoledronic acid.

Outcomes

Myocardial infarction and stroke (ischemic or hemorrhagic)

Data analysis plan

This study includes a descriptive analysis of the baseline prevalence of cardiovascular risk factors and incidence rates of the following outcomes of interest among post-menopausal women and men with osteoporosis initiating treatment with denosumab or zoledronic acid: MI, stroke, a composite outcome including MI and stroke, and a composite outcome including MI, stroke, and all-cause mortality (analysis of this last outcome is restricted to the Optum data base that contains information on death). If subjects in the two treatment groups are sufficiently comparable, based on quantitative assessment of balance in propensity scores between groups, the outcomes will be compared between treatment groups under the hypothesis that there exists no difference in rates of outcomes between subjects initiating treatment with denosumab versus those initiating treatment with zoledronic acid.