MS700568_0004: Pregnancy outcomes in women exposed to oral cladribine: a multi-country cohort database study (CLEAR)

Study type

• Study topic:
  Disease /health condition

  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:
  MAVENCLAD
• Study drug International non-proprietary name (INN) or common name:
  CLADRIBINE
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AA40) cladribine

  cladribine
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Short description of the study population:
  This study will enroll participants in a ratio of 1:2 between the cohort of pregnant women with Multiple Sclerosis (MS) exposed to oral cladribine to the cohort of pregnant women with MS unexposed to any DMD. ; Thus, aim is to enroll a total of 447 pregnant woman with 149 pregnant women with MS exposed to oral cladribine and 298 pregnant women with MS unexposed to any DMD. ; If the targeted sample size is not reached 5 years after the first feasibility check (pregnancy counts in the maternal cohort) in the study, recruitment will be stopped.
• Age groups:
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  447

Study design details

• Main study objective:
  To estimate prevalence of major congenital anomalies among infants of women with MS exposed to oral cladribine during and/or 6 months prior to pregnancy, and compare with prevalence in infants of pregnant women with MS unexposed to any disease modifying drug during or 3 months prior to pregnancy.
• Outcomes:
  Primary: Ocurrence of MCA (any and by type); Secondary: Occurrence of pregnancy outcomes(any)including spontaneous abortions; ectopic pregnancies; terminations of pregnancy due to foetal anomaly (TOPFA); terminations of pregnancy due to maternal risk (TOPMR)*; stillbirths: neonatal death; post-neonatal infant death, infant death and maternal death*; Occurrence of alterations in growth evident in foetuses at birth (eg,low birth weight [LBW], small for gestational age [SGA]); *only for pregnancies in female MS patients
• Data analysis plan:
  For each country, study variables will be described by study cohort. ; These variables will be used as potential confounders (if relevant) when comparing pregnancy outcomes between study cohorts. ; Descriptive statistics including number of outcomes (n) and prevalence (%, with corresponding 95% confidence interval [CI]) will be presented for each pregnancy outcome in each study cohort separately. ; The prevalence rate and prevalence difference between exposed and unexposed cohorts will be reported with corresponding 95%CI.; In each country, prevalence of pregnancy outcomes will be further compared between study cohorts using logistic regression with adjustments for potential confounders. ; The odds ratio (OR) estimates with 95% CI will be reported for these comparisons. ; Impact of exposure on each outcome will be assessed by stratification on timing of exposure (exposure will be categorized into trimesters based on cladribine start and stop dates) and on maternal age at LMP: Meta-analysis using aggregated results from each country database analysis will be performed.