RISK OF CARDIOVASCULAR EVENTS IN PATIENTS USING TOCILIZUMAB AS COMPARED WITH OTHER BIOLOGICS IN MULTIPLE LARGE HEALTHCARE DATABASES (EUPAS11327)

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  ACTEMRA
• Study drug International non-proprietary name (INN) or common name:
  TOCILIZUMAB
• Additional medical condition(s):
  Myocardial infarction,Acute coronary syndrome,Percutaneous coronary intervention,Coronary arterial stent insertion,Coronary artery bypass,Cardiac failure,Rheumatoid arthritis,Subarachnoid haemorrhage,Cerebral haemorrhage

Population studied

• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  76000

Study design details

• Main study objective:
  The primary objective is to compare time to first event of a composite of myocardial infarction and stroke (i.e. incidence rates) in patients newly treated with TCZ versus TNFi.
• Outcomes:
  The primary outcome of interest is a composite of non-fatal MI and non-fatal stroke (hemorrhagic, ischemic, uncertain classification). Non-fatal MI or non-fatal stroke is defined as events where patients were hospitalized with the occurrence of death shortly after arrival. The secondary outcome of interest include coronary revascularization (PTCA, stenting, CABG), acute coronary syndrome (ACS), a composite endpoint of primary cardiovascular events plus coronary revascularization procedures and ACS, heart failure (HF) requiring hospitalization, and all-cause mortality.
• Data analysis plan:
  Primary analyses will be a propensity scored matched, as-treated assessment on the primary and secondary outcomes evaluating (1) The incidence rate of the primary and secondary outcomes, (2) The absolute rate difference between initiators of TCZ and a comparator drug, (3) Time-to event analyses with Kaplan-Meier plots to inspect proportionality of hazards and assess whether follow-up time is comparable between treatment groups. Cox proportional hazard models will also be fitted to estimate hazard ratios (HR) and 95% confidence intervals (CIs).In addition to the aforementioned analyses, analyses will be stratified in mutually exclusive 6-month intervals of follow-up time since treatment initiation: 1 through 6 months, 7 through 12 months, etc. Multiple subgroups will be identified a priori and the analyses described above will be repeated. Additional sensitivity analyses will be carried out as well.