Emulation of a phase 3 study comparing Rituximab with Dimethyl Fumarate in early Relapsing-Remitting Multiple Sclerosis

Study type

• Study topic:
  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

Study drug and medical condition

• Study drug International non-proprietary name (INN) or common name:
  DIMETHYL FUMARATE

  RITUXIMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01FA01) rituximab

  rituximab

  (L04AX07) dimethyl fumarate

  dimethyl fumarate

Population studied

• Short description of the study population:
  Swedish multiple sclerosis patients registered in the Swedish Multiple Sclerosis registry
• Age groups:
  • Adult and elderly population (≥18 years)
• Special population of interest:
  Other
• Special population of interest, other:
  Swedish multiple sclerosis patients
• Estimated number of subjects:
  750

Study design details

• Study design:
  Target trial emulation following a strict and pragmatic scenario.; Retrospective new user active comparator cohort study.
• Main study objective:
  The objective is to emulate the comparative effectiveness of rituximab versus dimethyl fumarate in a real-world setting using strict inclusion/exclusion criteria and relaxed inclusion/exclusion criteria based on the results of a randomized, registry based phase 3 study (RIFUND-MS) to evaluate the effect in populations typically excluded from clinical trials but routinely treated in clinical practice. The secondary objective is to emulate the comparative effectiveness of rituximab and dimethyl fumarate on disease progression in a real-world setting using strict inclusion/exclusion criteria.
• Setting:
  Swedish multiple sclerosis patients registered in SMSreg initiating either rituximab or dimethyl fumarate.
• Comparators:
  Dimethyl fumarate (active comparator)
• Outcomes:
  Primary: Proportion of patients with relapse during the 24-month observational period.; Secondary: Time to first relapse, Proportion of patients free from all MRI activity during the 24-month observation period, EDSS-based 24 week Confirmed Disability Worsening (CDW), Change in EDSS from baseline to month 24, Drug persistence, No evidence of disease activity NEDA-2/-3, time to EDSS 4 and 6, time to SPMS.
• Data analysis plan:
  The proportion of patients with relapse during a 24 month observation period, the proportion of patients free from all MRI activity and the proportion of patients with confirmed EDSS score worsening will be analysed by log-binomial regression model similar to the RIFUND-MS trial. Time to 1st relapse, drug persistence, time to NEDA-2/-3 and time to confirmed sustained EDSS 4 and 6 and SPMS will be analysed by Cox Proportional Hazards regression. Inverse probability of treatment weighting (IPtW) will be applied to all analysis to mitigate confounding.