Retrospective Cohort Study of Pregnancy Outcomes in Women Exposed to Rimegepant During Pregnancy

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  VYDURA 75 MG - ORAL LYOPHILISATE
• Name of medicine, other:
  Nurtec ODT; Vydura
• Study drug International non-proprietary name (INN) or common name:
  RIMEGEPANT
• Anatomical Therapeutic Chemical (ATC) code:
  (N02CD06) rimegepant

  rimegepant
• Medical condition to be studied:
  Migraine

Population studied

• Short description of the study population:
  The source for the study population will consist of women who have been pregnant during the study period in the selected US data source. Pregnant women will have to fulfill the following eligibility criteria:; • Has a pregnancy code or a recorded pregnancy outcome (i.e., live birth, stillbirth, spontaneous abortion, or elective termination) within the study observation period; • Be aged 16 to 49 years, inclusive, at the estimated LMP within the study observation period.; ; In this population of pregnant women, we aim to identify 3 study groups:; • Pregnant women with migraine treated with rimegepant; • Pregnant women with migraine, unexposed to rimegepant, treated with other migraine medications; • Pregnant women without migraine, unexposed to rimegepant
• 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:
  8064

Study design details

• Study design:
  This is an observational, retrospective, cohort study using a single health care data source of prospectively collected secondary data. The source population will be pregnant women and their children born during the study period.
• Main study objective:
  The primary objective is to evaluate the risk of pregnancy and infant outcomes with major congenital malformations (MCMs) as the primary outcome of interest, and other primary outcomes including spontaneous abortions, fetal deaths/stillbirths, and small for gestational age (SGA) births among women with migraine exposed to rimegepant during pregnancy and in 2 rimegepant-unexposed comparator groups. ; ; Specific objectives are as follows:; • Objective 1: To describe patterns of use of rimegepant and other medications for migraine in pregnant women with migraine.; • Objective 2: To estimate the frequency of pregnancy outcomes (i.e., spontaneous abortions, fetal deaths/stillbirths, elective terminations), complications of pregnancy (i.e., preeclampsia/eclampsia), and fetal/infant outcomes (i.e., MCMs, SGA births, and preterm births) in women with migraine exposed to rimegepant during pregnancy and in 2 comparator groups of pregnant women not exposed to rimegepant ; • Objective 3: To estimate the adjusted relative risks (RRs) for the study outcomes among women exposed to rimegepant in pregnancy compared with the unexposed comparator groups.
• Setting:
  This study will be conducted in a US health care claims data source.
• Comparators:
  The primary comparator group will include pregnancies in women with migraine exposed to medications for the treatment of migraine other than rimegepant. ; Inclusion criteria:; • Have a migraine diagnosis that meets the criteria in Protocol Table 4 any time before the estimated LMP and through whichever is first: end of pregnancy or end of the study period; • Have at least 1 pharmacy dispensing for a medication indicated for the treatment of migraine within the 30-day time window before the estimated LMP and ending with whichever is first: end of pregnancy or end of the study period. Medications indicated for the treatment of migraine include NSAIDs, acetaminophen, triptans, ergots, opioids, betablockers, anti-epileptics, antidepressants, and botulinum toxin ; • Have a recorded outcome of pregnancy within the study period; • Had continuous enrollment in a health care plan with medical and pharmacy benefits during the 6-month period before the estimated LMP through a postpartum period of 42 days; Exclusion criterion:; • Have at least 1 pharmacy dispensing for rimegepant within the 30-day time window before the estimated LMP and through whichever is first: end of pregnancy or end of the study period; ; The secondary comparator group will include rimegepant-unexposed pregnancies in women without migraine. ; Inclusion criteria:; • Have no migraine diagnosis that meets the criteria in Protocol Table 4 any time before the estimated LMP through whichever is first: end of pregnancy or end of the study period; • Have a recorded outcome of pregnancy within the study period; • Had continuous enrollment in a health care plan with medical and pharmacy benefits during the 6-month period before the estimated LMP through a postpartum period of 42 days; Exclusion criterion:; • Have at least 1 pharmacy dispensing for rimegepant within the 30-day time window before the estimated LMP through whichever is first: end of pregnancy or end of the study period.
• Outcomes:
  The primary outcome of interest is:; • Major congenital malformations; ; Other primary outcomes are the following:; • Spontaneous abortions; • Fetal deaths/stillbirths; • Small for gestational age births; ; The secondary outcomes are the following:; • Elective terminations; • Pre-eclampsia or eclampsia (combined), during pregnancy and through the postpartum period; • Preterm births.
• Data analysis plan:
  A drug utilization analysis of use of rimegepant and other migraine medications will include number of users and mean, standard deviation, median, IQR of number of dispensings, and number of days between consecutive dispensings for each medication group. ; A description of the cohort attrition, selected characteristics of pregnancies in each exposure group, and frequency of study outcomes will be reported for each study group. ; For the safety comparative analyses, if feasible, the study groups will be matched on propensity scores to control for confounding and channeling. ; Each woman in the rimegepant-exposed group will be matched in a 1:n variable-matching ratio with up to 3 women in each of the comparator groups (separately). Regression models will be used to compare pregnant women with migraine exposed to rimegepant with women in the primary comparator group and in the secondary comparator group. ; Point estimates and 95% CIs from analyses within the matched study groups will be presented.