Study identification

EU PAS number

EUPAS3435

Study ID

26688

Official title and acronym

The safety of anti-tumor necrosis factor-α (TNF-α) agents in pregnancy. An observational prospective multicenter study (TNF-α Blocker in Pregnancy)

DARWIN EU® study

No

Study countries

Australia
Finland
France
Germany
Italy
Netherlands
Switzerland
Türkiye
United Kingdom

Study description

The five TNF-alpha inhibitors adalimumab, certolizumab pegol, etanercept, golimumab and infliximab are not labeled for use in pregnancy. Existing experience during pregnancy does not suggest teratogenicity, but varies between the different substances and altogether is still limited. Furthermore, there are concerns against the use of TNF-α inhibitors in late pregnancy, because at least some of them exhibit an increasing placental transfer during the course of pregnancy. This results in therapeutic fetal/neonatal plasma concentrations. A case report of a newborn raises concern. The mother was treated with infliximab throughout pregnancy. The 3-months old infant received BCG live-vaccination resulting in disseminated BCG infection and ultimately in the death of the child (Cheent 2010). Our prospective multicenter cohort study enrolls women who have spontaneously contacted a teratology information service (TIS) within the European Network (ENTIS). The sample of exposed pregnancies includes women who were treated with a TNF-alpha inhibitor during the first trimester (part 1). The comparison group consists of non-exposed women matched for year of enrollment and TIS. The focus lies on the risk of birth defects (BD), spontaneous abortion, and low birth weight. Part 2 evaluates potential impacts of maternal TNF-α inhibitors on the infant’s immune system during the 1st year of life. It is an explorative cohort study including infants born ≥ 34.0 weeks without major BD. Prerequisite are access to data regarding the pregnancy course within 8 weeks after delivery and no information on the further development of the child. Exposed women may have been treated at any time during pregnancy, but special interest lies on an exposure period > 20 weeks of gestation. Exposed infants are compared to non-exposed children matched for sex, gestational week at birth, birth weight, and year of birth. Cases exposed to major teratogens or fetotoxicants are excluded from all groups of both parts.

Study status

Ongoing
Research institutions and networks

Institutions

Networks

Contact details

Corinna Weber-Schoendorfer

Primary lead investigator

Study timelines

Date when funding contract was signed

Planned:
Actual:

Study start date

Planned:
Actual:

Data analysis start date

Planned:
Actual:

Date of final study report

Planned:
Sources of funding
Other

More details on funding

Bundesministerium für Gesundheit, Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM)
Regulatory

Was the study required by a regulatory body?

No

Is the study required by a Risk Management Plan (RMP)?

Not applicable