Long-Term Surveillance of Ocrelizumab-Treated Patients With Multiple Sclerosis (MANUSCRIPT Study)

Study type

• Study topic:
  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:
  OCREVUS
• Study drug International non-proprietary name (INN) or common name:
  OCRELIZUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AG08) ocrelizumab

  ocrelizumab
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Short description of the study population:
  This study will include patients with multiple sclerosis (MS) who have initiated treatment with ocrelizumab or another disease modifying therapy (DMT) during the study period, or patients with MS not on DMT therapy in routine clinical practice.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  8500

Study design details

• Study design:
  This is a multi-source, multi-country, non-interventional, longitudinal cohort study based on secondary use of data captured for patients with MS in existing disease registries.
• Main study objective:
  The research question is to assess and characterize the long-term safety data from theuse of ocrelizumab in patients with MS (overall and by MS type).
• Comparators:
  1) Disease modifying therapy (DMT) comparator group:; Patients who have never received treatment with ocrelizumab (at any time in the complete available history) and must be newly treated with an approved DMT other than ocrelizumab during the study observational period.; ; 2) Non-DMT comparator group:; Patients who have never received ocrelizumab or any other DMT within the complete history recorded within available medical records and during individual follow-up in the study observational period;
• Outcomes:
  The primary objective is to estimate (overall and by MS type) the event rates of serious adverse events (SAEs), including malignancy, serious infections, and drug-induced liver injury, following ocrelizumab treatment in patients with MS.
• Data analysis plan:
  The number of safety events and unadjusted incidence rates with 95% confidence intervals will be provided for each treatment group, ocrelizumab and other DMTs, for each data source. For malignancy and progressive multifocal leukoencephalopathy (PML), an ever-exposed model will be applied that includes all person-time observed since the first drug dose in the study until censorship. For all other SAEs, a time-on-drug approach will be used. For analyses of death, both approaches will be used. Comparison between ocrelizumab and other DMTs, at year 4, 6, 8, and end of the study, will be based on a Cox proportional-hazards regression model adjusted for important covariates and probability of treatment with ocrelizumab.