A non-interventional post-authorisation safety study to investigate the risk of mortality in multiple sclerosis patients treated with alemtuzumab (LEMTRADA®) relative to comparable multiple sclerosis patients using other disease modifying therapies: a cohort study

Study type

• 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

• Study drug International non-proprietary name (INN) or common name:
  ALEMTUZUMAB
• Medical condition to be studied:
  Multiple sclerosis

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:
  9000

Study design details

• Main study objective:
  The primary objective is to ascertain whether multiple sclerosis (MS) patients treated with LEMTRADA have a higher risk of all-cause mortality than comparable MS patients treated with other HE-DMT.
• Outcomes:
  The primary outcome is the all-ause mortality, The secondary outcome is the cause-specific mortality. This secondary outcome will be exploratory as it is anticipated that availability and quality of cause-specific mortality data will be variable across data sources.
• Data analysis plan:
  The following statistical analyses will be conducted separately in each data source: - Descriptive statistics - Crude and age-standardised mortality rates will be computed by exposure group (LEMTRADA vs other HE-DMT), for all MS patients and by gender. - Propensity score (PS) model will be constructed in order to create two comparable groups of patients with similar distributions of risk factors (LEMTRADA vs other HE-DMT). PS weight will be computed using the standardised mortality ratio method. - Risk of death among the LEMTRADA group compared to the other HE-DMT group will be expressed as hazard ratio (HR) and computed from a PS weighted time-dependent Cox proportional hazards model that will include a time-dependent exposure. A meta-analysis will be performed by iPRI to combine all HR from each data source in order to obtain a global estimate of the risk of death in the LEMTRADA group compared to the other HE-DMT group.

Documents

Study, other information

lem_pass_mort_protocol_may192021