The Safety Assessment of Vedolizumab During Pregnancy in IBD Patient

The safety assessment of Vedolizumab during pregnancy in IBD patients.

The primary objective of this study is:

1. To quantify incidence of major structural birth defects and other birth outcomes in infants born to women with UC/CD with exposure to Entyvio compared to women with exposure to other biological agents or conventional IBD therapy during pregnancy
2. To assess the health and developmental status of infants up to 1yr of age.

Study Overview

• Status: Unknown
• Conditions: Pregnancy Complications

Detailed Description

The IBD MOM clinic currently follows women with IBD from the preconception stage through postpartum period. In addition, we have now started following the offspring for 1 year with an option of extending the follow up until 4 years after birth with participation of the family health center. Data is collected longitudinally on use of non-immunomodulator medications, AZA/6MP, biologic therapy infliximab, adalimumab, certolizumab, and natalizumab. Corticosteroids,5-ASA and Methotrexate), disease activity during gestation, complications of pregnancy and delivery, and infant birth outcomes during the first year of the child's life because from population-based data, including the Kaiser sample1 and studies from Europe2-4 women with IBD clearly have an increased risk of adverse pregnancy outcomes such as preterm birth and/or low birth weight infants, even with inactive disease.10.

Study duration: September 2015- September 2022 This is a non-interventional observational prospective cohort study to be conducted in an actual clinical practice setting.

This is an exposure-based cohort study in which there will be 3 reference groups. Women on conventional therapy only, women on Vedolizumab and women on other biologics.

The source database contains information collected from our IBD MOM clinic in Shaare Zedek Medical Center in Jerusalem, Israel.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Ariella Shitrit, PHD; Phone Number: 216 972-2-6555555; Email: ariellash@szmc.org.il

Study Locations

• Israel
  • Jerusalem, Israel
    • Recruiting
    • Shaarey Zedek MC
    • Contact: Ariellah Shitrit, PHD; Phone Number: 216 972-2-655555; Email: ariellash@szmc.org.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

The source population is women attending the IBD MON clinic at Shaare Zedek Medical Center in Jerusalem, Israel.

Description

Inclusion Criteria for the UC/CD Prospective Cohort:

• The subject is a currently pregnant woman with UC or CD
• The subject has exposure to Entyvio or other biologic agents or conventional therapy (non-biological therapy) at any dose, and at any time from first day of LMP, The subject enrolls no later than 19 completed weeks after LMP.
• All pregnancies in Entyvio users will be included in the study. Those recruited prior to Week 20 will be entered into the prospective registry, and those recruited after week 20 (included retrospective reports after delivery) will be entered into the separate Case Series.
• The subject agrees to the conditions and requirements of the study including the interview schedule, release of medical records, and the physical examination of live born infants.

Exclusion Criteria for the UC/CD Prospective Cohort:

• The subject is >19 completed weeks gestation prior to enrollment,
• The subject has first contact with OTIS after prenatal diagnosis of any major structural defect,
• The subject has enrolled in this registry with a previous pregnancy,

• The subject has had an exposure to the known or suspected human teratogens:

  • Chlorambucil
  • Cyclophosphamide
  • Mycophenylate mofetil

Any Entyvio exposed mother who does not meet the entry criteria will be entered into an Entyvio case series, which will be used to provide support data to cohort study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Vedolizumab Cohort; Group 1a Mothers exposed to Vedolizumab at any time during pregnancy (and up to 3 months prior to last menstrual period [LMP], if this information is available).; Group 1b Infants born to Group 1a patients.
Anti-TNF Agents Cohort; Group 2a Patients with IBD who were exposed to anti-TNFs at any time during pregnancy (and up to 3 months prior to LMP, if this information is available).; Group 2b Infants born to Group 2a patients.
Conventional therapy only Cohort; Patients with IBD who were exposed to conventional therapy only any time during pregnancy (and up to 3 months prior to LMP, if this information is available). • Group 3b Infants born to Group 3a patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major body measurements defects of the infant	A major Body measurements defect is defined as a defect that has either cosmetic or functional significance to the child (eg, a cleft lip), as defined by the Centers for Disease Control and Prevention (CDC; [4]). These defects in aggregate typically occur in <4% of the general population. Over 100 specific structural defects are considered to be major. Measurements of head circumference, length, weight, palpebral fissure length, inner canthal distance, ear length, and philtrum length will be taken. These will be compared to mean values for infants of the same age and sex (where sex-specific normative data are available). Less than or greater than 2 standard deviations from the mean will be used to define such terms as microcephaly, hypertelorism, etc.	1 year from birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minor body measurements defects of the infant	A minor structural defect is defined as a defect that has neither cosmetic nor functional significance to the child (eg, complete 2,3 syndactyly of the toes) and is identified using a study-related checklist incorporated into the study dysmorphology examination of live born infants. Measurements of head circumference, length, weight, palpebral fissure length, inner canthal distance, ear length, and philtrum length will be taken. These will be compared to mean values for infants of the same age and sex (where sex-specific normative data are available). Less than or greater than 2 standard deviations from the mean will be used to define such terms as microcephaly, hypertelorism, etc.	1 year from birth

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Spontaneous abortion	Non-deliberate embryonic or fetal death	Prior to 20 weeks' gestation post-LMP
Rate of Elective abortion	Deliberate termination of pregnanc. Reason for elective abortion will be ascertained.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Rate of Stillbirth	A non-deliberate fetal death	After 20 weeks' gestation post-LMP, but prior to delivery
Rate of Premature delivery	Defined as live birth. Elective caesarian deliveries or inductions prior to 37 completed weeks are not considered premature deliveries, and will be considered separately.	Prior to 37 completed weeks' gestation post-LMP.
Rate of SGA	Weight, length or head circumference. less than or equal to the 10th percentile for sex and gestational age using standard pediatric CDC growth curves for full term or preterm infants	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Rate of Postnatal growth deficiency	Weight, length or head circumference) less than or equal to the 10th percentile for sex and age using National Center for Health Statistics (NCHS) pediatric growth curves, and adjusted postnatal age for premature infants if the postnatal measurement is obtained at less than 1 year of age.	The size of the infant at the time of postnatal until 1 year of age
Rate of Lost-to-follow-up following the estimated due date	Is defined as an enrolled subject where follow-up information on the outcome (live birth, fetal loss) is not obtainable, or for a live birth if the birth defect status is designated as "unknown". The OTIS Autoimmune Diseases in Pregnancy Project has experienced extremely low losses to follow-up (<5% of enrolled subjects) by virtue of maintaining consistent contact with the pregnant woman. Before a subject is designated as lost to follow up, the subject or reporter receives at least 3 reminder telephone calls (documented in the database) followed by written correspondence and alternative contact information that is requested upon enrollment is utilized. Voluntary subject withdrawals will be considered separately.	12 months following the estimated due date
Rate of Serious or opportunistic infections	Defined as those listed in Error! Reference source not found., and identified in newborn infants up to 1 year of age, or infections that require hospitalization up to 1 year of age. Pediatric records will be requested with specific requests for documentation of hospitalizations and opportunistic infections.	Newborn infants up to 1 year of age
Rate of Malignancies	Defined as any malignancy reported in an infant up to 1 year of age. Pediatric records will be requested with specific requests for documentation of malignancies.	Up to 1 year of age of the infant

Collaborators and Investigators

• Sponsor: Ariella Shitrit
• Investigators: Study Director: Eran Goldin, Professor, Shaarey Zedek MC

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: November 19, 2015
• First Submitted That Met QC Criteria: November 26, 2015
• First Posted (Estimate): December 1, 2015

Study Record Updates

• Last Update Posted (Actual): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications
• Other Study ID Numbers: szmc 2015-001