Long-term effectiveness of cladribine in patients previously treated with oral cladribine: a Real-World Evidence analysis using data from the Italian Registry of Multiple Sclerosis (CLARINET-MS)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Non-interventional cohort RWE study

Study drug and medical condition

• Name of medicine:
  MAVENCLAD
• 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:
  161

Study design details

• Main study objective:
  Clinical practice data from Italian MS patients who received at least one course of cladribine tablets treatment in pivotal clinical trials are continuously and consistently collected in digital database iMedWeb on entire Italian territory. Study will shed light whether long-termeffectiveness of cladribine tablets can be supported by data currently available in Italian MS patient registry.
• Outcomes:
  To assess the time-to-treatment change in clinical practice as surrogate marker for long-term effectiveness of cladribine in subjects with the clinical isolated syndrome (CIS) or remitting multiple sclerosis (RMS) phenotypes, Time-to-disability progression, Time-to-first EDSS ≥ 6.0, ≥ 7.0, Time-to-relapse during observational period, Number of Disease Modifying Treatments (DMTs) after last cladribine tablets course in subjects with CIS, RRMS or SPMS Incidence of conversion of subjects with CIS to a clinically defined MS (CDMS)
• Data analysis plan:
  Statistical testing will not be done as the nature of the study is descriptive and there is no hypothesis testing to be performed.Primary outcome time-to-treatment change as well as secondaryoutcome time-to-disability progression, time-to-first EDSS ≥ 6.0, time to-first EDSS ≥ 7.0 and time-to-relapse will be analyzed by means oftime-to-event analysis based on Kaplan-Meier method. Medianduration and its associated 95% Confidence Intervals (CIs) will beestimated from model. Analyses will be repeated by using gender, MS phenotype, RCT type and categorized age groups, EDSS score, number of relapses before RCT+1 and time since diagnosis as strata. Further, incidence of conversion from CIS to CDMS will be estimatedand number of treatments after last cladribine tablets course will betabulated.In case of unanticipated outcomes, additional ad hoc analyses will be performed to further investigate the data. Any missing data in RWE data will be assumed to be missing at random.