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

  Safety 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

• Medicinal product name:
  MAVENCLAD
• Study drug International non-proprietary name (INN) or common name:
  CLADRIBINE
• Anatomical Therapeutic Chemical (ATC) code:
  (L01BB04) cladribine

  cladribine
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Short description of the study population:
  The study population will consist of Italian MS patients distributed across 26 Italian MS centers. ; The selection of the MS patients will be based on the following criteria: ; Inclusion criteria: ; • Prior enrollment into oral cladribine pivotal clinical trials with at least one course of cladribine tablets treatment and participation in the clinical trial has ended ; • Written informed consent was given to the patient registry ; Exclusion criteria ; • No exclusion criteria have been set-up for this non-interventional study.
• 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

• Study design:
  This study is a non-interventional, exploratory investigation of a cohort of patient registry data currently available in iMedWeb from Italian MS patients who received at least one course of cladribine tablets treatment in the cladribine clinical development trials.
• 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.
• Setting:
  The Italian digital patient registry iMedWeb continuously and consistently collects RWE data from 134 MS clinical centers spread across the entire Italian territory. The registry requires MS patients to provide a signed informed consent to allow their data upload into the registry. Only data from Italian MS patients who have participated into the cladribine tablets pivotal randomized clinical trials and who received at least one course of cladribine tablets treatment will be extracted in anonymized form from the registry for the analyses proposed in this study.
• 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.