A Retrospective, Multi-Center, Observational Study to Assess the Effect of Tecfidera® Delayed-Release Capsules on Lymphocyte Subsets in Subjects with Relapsing Forms of Multiple Sclerosis (REALIZE)

Study type

• Study topic:
  Disease /health condition

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

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Retrospective, observational study

Study drug and medical condition

• Name of medicine:
  TECFIDERA
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Short description of the study population:
  Adult patients with relapsing forms of MS who were receiving or received Tecfidera for at least 6 months in routine clinical practice.
• 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)
• Special population of interest:
  Other
• Special population of interest, other:
  Multiple sclerosis patients
• Estimated number of subjects:
  483

Study design details

• Main study objective:
  The primary objective of the study is to retrospectively investigate changes in lymphocyte counts and lymphocyte subtypes, with a focus on CD4+ and CD8+ T cells, in participants on Tecfidera therapy for at least 6 months.
• Outcomes:
  • Estimated absolute lymphocyte count (ALC) change from baseline following Tecfidera initiation• Estimated CD4+ count change from baseline following Tecfidera initiation• Estimated CD8+ count change from baseline following Tecfidera initiation, • Raw absolute counts for leukocyte, lymphocyte, CD4+/CD8+ ratio following Tecfidera initiation • Raw absolute counts for additional lymphocyte subsets (other than CD4+ and CD8+) • Change from baseline for leukocyte, lymphocyte, CD4+/CD8+ ratio following Tecfidera initiation • Change from baseline for additional lymphocyte subsets (other than CD4+and CD8+) following Tecfidera initiation
• Data analysis plan:
  For the primary analysis changes from baseline in Lymphocyte, CD4, and CD8 counts will be analyzed separately using a repeated measures mixed effects model (RMMM). In addition descriptive statistics will be presented for at 6 and 12 Months for absolute values, the change and percent change from baseline. Kaplan-Meier curves will estimate the time to pre-determined lymphocyte counts following the start of Tecfidera therapy. An analysis of covariance and logistic regression models will be evaluated to determine potential predictors of low lymphocyte counts. Descriptive statistics will be used to summarize lymphocyte counts and subsets post discontinuation. Similar analyses will be performed for the additional lymphocyte subsets and CD4/CD8 ratio.The association between opportunistic and serious infections and WBC, lymphocytes, CD4 as well as CD8 counts will be evaluated with a Fisher’s exact and Barnard’s exact test.