Safety and Effectiveness of Ocrelizumab under Real World Conditions: a Non-Interventional Post Authorization Safety Study in Patients Diagnosed with Relapsing or Primary Progressive Multiple Sclerosis (CONFIDENCE)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  OCREVUS
• 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:
  3767

Study design details

• Main study objective:
  To assess the long-term safety, with special focus on the occurrence and characterization of uncommon AEs in patients with MS newly exposed to ocrelizumab.
• Outcomes:
  Incidence and type of uncommon AEs (i.e. AEs with an incidence rate of at least 0.1% to 1% 1 to 10 out of 1000 patients or less) and death with primary and underlying causes in patients with MS newly exposed to ocrelizumab. - incidence and type of uncommon AEs and death with primary and underlying causes in patients with MS newly exposed to selected MS DMTs other than ocrelizumab -treatment success -proportion of patients with relapses -proportion of patients with CDP -time to onset of CDP and CDI -patient reported outcomes -incidence of AEs, serious infections, malignancies, mortality rate due to malignancies
• Data analysis plan:
  The primary endpoint will be analyzed for each combination of cohort treated with ocrelizumab, MS type and Safety Set. Frequencies of adverse events will be calculated based on MedDRA coding and presented with two-sided 95% Clopper-Pearson intervals. Analogously, the key secondary endpoint will be analyzed for the cohort treated with other DTMs. Effectiveness analyses will be conducted on each combination of cohort, MS type and Full Analysis Set. Secondary, exploratory and other endpoints will be analyzed descriptively. Depending on the endpoint, a logistic, negative binomial, linear or ANCOVA model will be fitted. Time-to-event data will be analyzed with Kaplan-Meier. Other safety analyses will be conducted analogously to the primary endpoint. For safety endpoints time adjusted analyses based on patient years will be performed. To investigate potential channeling effects, a sensitivity analysis of selected endpoints will be performed based on various time spans of patients enrolled.