Post-Authorization Safety Study for Assessment of Pregnancy and Infant Outcomes in Patients Treated with Kesimpta (ofatumumab) using OTIS Observational Pregnancy Surveillance Program and DMSKW Registry (Kesimpta Pregnancy Registry)

Study type

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

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  KESIMPTA
• Study drug International non-proprietary name (INN) or common name:
  OFATUMUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AA52) ofatumumab

  ofatumumab
• Medical condition to be studied:
  Multiple sclerosis

Population studied

• Age groups:
  Preterm newborn infants (0 – 27 days)

  Term newborn infants (0 – 27 days)

  Infants and toddlers (28 days – 23 months)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  725

Study design details

• Main study objective:
  The primary objective is to estimate and compare the prevalence of major structural defects in fetus/infants born to Kesimpta exposed pregnant women with MS versus 1) disease-matched pregnant women not exposed to Kesimpta, and 2) healthy pregnant women.
• Outcomes:
  The primary outcome of the study is major structural birth defect.; Secondary outcomes:; - Spontaneous abortion/miscarriage ; - Stillbirth ; - Elective termination ; - Preterm delivery ; - Preeclampsia / eclampsia ; - Pattern of 3 or more minor structural defects ; - Small for gestational age ; - Postnatal growth small for age at one year of age ; - Developmental performance at approximately one year of age ; - Serious or opportunistic infections in the first year
• Data analysis plan:
  The primary outcome will be estimated in each cohort as a proportion (95% confidence interval) in pregnancies ending in at least one live born infant. As primary comparison, the crude RR and 95% CI for Kesimpta-exposed cohort vs. disease-Matched cohort will be estimated. Due to the observational nature of the study, the crude RR estimate will be further adjusted for potential confounders using propensity score (PS) methods. The primary analysis will be performed using the PS via inverse probability of treatment weighting. The secondary endpoints spontaneous abortion/miscarriage, stillbirth and premature delivery will be analyzed using survival analysis methods, elective termination, preeclampsia/eclampsia, small for gestational age will be analyzed like the primary outcome. Since multiple births will be included, minor structural defects, ASQ, and serious or opportunistic infections will be analyzed using generalized estimating equations approach.