Observational Cohort Study of Ritlecitinib Safety in Pregnancy within a US Claims Database

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine, other:
  Ritlecitinib
• Study drug International non-proprietary name (INN) or common name:
  RITLECITINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L04AF08) ritlecitinib

  ritlecitinib

Population studied

• Short description of the study population:
  Pregnancies among individuals with alopecia areata (AA) with an estimated conception date (ECD) between 23 June 2023 and 03 August 2033 with follow-up for outcomes through 23 June 2034.
• Special population of interest:
  Pregnant women

Study design details

• Study design:
  Cohort study within two US-based health insurance claims databases. Three cohorts will be identified: pregnancies exposed to ritlecitinib, a treated comparator cohort exposed to other approved alopecia areata (AA) therapies, and a second treated comparator cohort exposed to other AA therapies.
• Main study objective:
  Primary objectives:; 1. To estimate the prevalence of major congenital malformation (MCM) livebirths among pregnant individuals with AA who are (1) exposed to ritlecitinib; (2) unexposed to ritlecitinib but exposed to other approved treatments for AA; and (3) unexposed to ritlecitinib but exposed to other treatments for AA.; 2. To estimate the relative prevalence of MCM livebirths in the ritlecitinib-exposed cohort versus the two comparator cohorts.; Secondary objectives:; 1. To estimate the prevalence of the following secondary outcomes in the study cohorts: spontaneous abortion, pregnancy termination, stillbirth, pregnancy-related hypertension, gestational diabetes, pre-eclampsia, eclampsia, small for gestational age (SGA) birth, preterm birth, and serious infection in the first year of life.; 2. To estimate the relative prevalence of each of the secondary outcomes in the ritlecitinib-exposed cohort versus the two comparator cohorts, if sample size permits.
• Setting:
  The base population will include all pregnancies among individuals with AA identified during the study period within the US-based health insurance claims databases.
• Comparators:
  The approved treated comparator cohort (Cohort 2) will include eligible pregnancies exposed to a medication indicated for the treatment of severe AA other than ritlecitinib, and not exposed to ritlecitinib or other JAK inhibitors not approved for the indication of severe AA. Pregnancies may be eligible for this cohort if they are also exposed to other, non-approved, treatments for AA (non-JAK inhibitors), including those used to define Cohort 3. ; ; A second treated comparator cohort (Cohort 3) will include pregnancies exposed to medications or procedures reported in the literature as being used for treatment of extensive or severe AA, but which have not received FDA approval for that indication. Treatments included in this cohort need not have demonstrated effectiveness for the treatment of AA; rather, they are often used in real world practice.
• Outcomes:
  The primary outcome is validated major congenital malformation. The secondary outcomes are spontaneous abortion, pregnancy termination, stillbirth, pregnancy-related hypertension, gestational diabetes, pre-eclampsia, eclampsia, small for gestational age birth, preterm birth, and serious infection in the first year of life.
• Data analysis plan:
  For interim reports all analyses will be descriptive, including the number of observations, mean, standard deviation, median, interquartile range, and range for all continuous variables and counts and percentages for each binary or categorical variable. ; The interim report will additionally include claims-identified outcome counts aggregated across cohorts (in order to blind cohort membership). ; Validation of MCMs via medical record review will not be performed until the final report analysis.; ; For the final report, prevalence and 95% confidence intervals (CIs) for each of the study outcomes will be estimated separately for each study cohort and each database. ; For MCM, the final analyses will be restricted to confirmed cases. Prevalence estimates and comparative analyses will be restricted to pregnancies with an observed pregnancy outcome in the claims data.; ;