Post-marketing Study Assessing the Serious Cardiovascular Events Among Osteoporotic Patients Initiating Romosozumab in Japan Using the Medical Information Database Network (MID-NET) (20190206)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  EVENITY
• Study drug International non-proprietary name (INN) or common name:
  ROMOSOZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (M05BX06) romosozumab

  romosozumab
• Medical condition to be studied:
  Osteoporosis

  Myocardial infarction

  Cerebral haemorrhage

  Cerebral infarction

Population studied

• Short description of the study population:
  Patient Eligibility Criteria ; Inclusion criteria ; - Three cohorts of patients defined by new initiation of romosozumab, Parathyroid hormone 1 receptor (PTH1R) agonists (teriparatide, abaloparatide) or oral alendronate from 4 March 2019 onwards to one year prior to the end of available data. ; - Patients at least 50 years of age at the date of new treatment initiation. ; Exclusion criteria ; - Patient without an adequate period of records in the data source for assessment of baseline cardiovascular risk.
• 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:
  3850

Study design details

• Study design:
  Retrospective cohort study employing a new user with active comparator design
• Main study objective:
  The main study objective is to assess the serious cardiovascular events of romosozumab and other osteoporosis medications among osteoporotic patients overall and with/without renal dysfunction in Japan.
• Setting:
  MID-NET database is a hospital-based setting of 23 hospitals from ten healthcare organizations.
• Comparators:
  patients initiating other specific osteoporosis therapies.; ;  romosozumab vs. PTH1R agonists ;  romosozumab vs. oral alendronate
• Outcomes:
  Primary outcome:; • Composite endpoint of hospitalized acute myocardial infarction, cerebral hemorrhage and cerebral infarction; ; Secondary outcome:; • Composite endpoint of hospitalized acute myocardial infarction, cerebral hemorrhage and cerebral infarction
• Data analysis plan:
  [Approach to primary objective]; Propensity scores will be calculated for each patient using multiple logistic regression modelling based on baseline demographic characteristics and clinical characteristics. Inverse probability of treatment weights (IPTW) will be created using propensity scores to minimize the measured confounding in the comparison of patients initiating romosozumab relative to patients initiating other specific osteoporosis therapies. Standardized mean differences (SMD) will be used to assess the differences in baseline patient characteristics between the treatment groups. Negative control outcome analyses will be used to detect presence of unmeasured confounding. COX proportional hazards model in the weighted sample will be used to estimate hazard ratio.; ; [Approach to secondary objective]; The same approach will be performed by the level of renal insufficiency.