Tofacitinib Pregnancy Exposure Registry OTIS Autoimmune Diseases in Pregnancy Project (OTIS PASS Tofacitinib)

Study type

• Study topic:
  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

• Name of medicine:
  XELJANZ
• Medical condition to be studied:
  Rheumatoid arthritis

  Psoriatic arthropathy

  Colitis ulcerative

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Neonate

      • Preterm newborn infants (0 – 27 days)
      • Term newborn infants (0 – 27 days)
    • Infants and toddlers (28 days – 23 months)
  • Adult and elderly population (≥18 years)
• Special population of interest:
  Pregnant women
• Estimated number of subjects:
  300

Study design details

• Study design:
  This is a prospective, observational cohort study of pregnancy outcomes in women with a disease for which tofacitinib has an approved indication who are exposed to tofacitinib during pregnancy.
• Main study objective:
  The main objective of the study is to conduct an observational cohort study that will involve follow-up of live born infrants to one year of age to assess the potential increase in the risk of birth defects in pregnancies exposed to tofacitinib compared with an unexposed comparator population.
• Setting:
  The cohort study will be conducted by the Organization of Teratology InformationSpecialists (OTIS) which is a network of university and health department based telephone information centers serving pregnant women and healthcare providers throughout North America. These services receive spontaneous telephone inquiries from women and health care providers about the safety or risk associated with environmental exposures in pregnancy,; including medications. Trained Teratogen Information Specialists at each site provide appropriate risk assessment and referral for all patient and health care provider callers free of charge. These services also provide a basis for collaborative research such as this Registry. Thus, individual Teratogen Information Services located throughout the U.S. and Canada will serve as a source of referrals not only for tofacitinib-exposed pregnancies but also for; similarly-ascertained pregnant women with an approved indicated disease who have not used tofacitinib and similarly ascertained pregnant women without an autoimmune disease who have not used tofacitinib or any known human teratogen. As OTIS member services receive over 70,000 teratogen information telephone inquiries per year, OTIS members constitute a major source of identification and recruitment of exposed women and appropriate comparison women. Once women are in contact with the Registry Coordinating Center, enrollment in the Registry is voluntary and requires informed consent of the pregnant woman. The Registry will enroll pregnant women who are less than 20 weeks’ gestation. This is accomplished by encouraging clinicians to refer patients, and following-up with women who are planning pregnancy who contact an OTIS service or who self-refer, and; direct outreach efforts to target women who are less than 20 weeks’ gestation. These efforts reduce possible bias based on prior knowledge of a normal ultrasound, and allow for better estimation of risk of spontaneous abortion.;
• Comparators:
  Comparison Group I: Disease-matched Unexposed (to tofacitinib) Cohort: ; Currently pregnant women with a diagnosis of a disease for which tofacitinib has an approved indication, by maternal report and validated by medical records, who have not taken tofacitinib any time since first day of last menstrual period (LMP) to delivery in the current pregnancy but who may or may not have taken another medication for their disease including an anti-TNF or other biologic in the current pregnancy. To the extent that tofacitinib-exposed women enrolled in the cohort study also have methotrexate exposure, women in the disease-matched unexposed comparison group I with methotrexate exposure will be recruited to frequency match the number with tofacitinib plus methotrexate, and who agree to enroll prior to 20 weeks’ gestation, and who have not had prenatal diagnosis of any major structural defect prior to enrollment.; ; Comparison Group II: Non-diseased Unexposed (to tofacitinib) Cohort: ; Currently pregnant women who have not had exposure to a known human teratogen or biologic agent as confirmed by the OTIS Research Center, and who do not have an autoimmune disease, and who agree to enroll prior to 20 weeks’ gestation, and who have not had prenatal diagnosis of any major structural defect prior to enrollment.;
• Outcomes:
  The primary outcome variable is major structural defects. Secondary outcomes include: minor structural defects, spontaneous abortions, stillbirth, premature delivery, small for gestational age, postnatal growth deficiency, loss to follow-up, serious or opportunistic infections and malignancies.
• Data analysis plan:
  The primary analysis for the cohort study will be a comparison of the birth prevalence of major structural defects in live born infants between the tofacitinib-exposed group and the primary comparator group. This analysis will use chi-square or Fisher’s Exact test for univariate comparisons and logistic regression or Cochran-Mantel-Haenzsel test for multivariate analysis (ie, adjustment of possible confounders including demographics and disease duration).