Status: Ongoing First registered on: 28/01/2013
Last updated on: 23/11/2018
1. Study identification
EU PAS Register NumberEUPAS3435
Official titleThe safety of anti-tumor necrosis factor-α (TNF-α) agents in pregnancy. An observational prospective multicenter study
Study title acronymTNF-α Blocker in Pregnancy
Study typeObservational study
Brief description of the studyThe 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.
Was this study requested by a regulator?No
Is the study required by a Risk Management Plan (RMP)? Not applicable
Regulatory procedure number (RMP Category 1 and 2 studies only)
Other study registration identification numbers and URLs as applicable
2. Research centres and Investigator details
Coordinating study entity
Centre to which the investigator belongsEmbryotox Berlin
Department/Research groupPharmakovigilanzzentrum Embryonaltoxikologie
Organisation/affiliationCharité-Universitätsmedizin
Website/Homepagewww.embryotox.de
Details of (Primary) lead investigator
Title Dr
Last name Weber-Schoendorfer
First name Corinna
Is this study being carried out with the collaboration of a research network?
Yes

ENTIS
Other centres where this study is being conducted
Not applicable (single centre)

Countries in which this study is being conducted
International study

Australia
Finland
France
Germany
Italy
Netherlands
Switzerland
Turkey
United Kingdom
3. Study timelines: initial administrative steps, progress reports and final report
PlannedActual
Date when funding contract was signed02/01/201229/05/2012
Start date of data collection23/09/201302/09/2013
Start date of data analysis03/03/201420/03/2014
Date of interim report, if expected
Date of final study report31/12/2014
4. Sources of funding
Please provide estimates of the percentage of funding by source for this study
Names(s)Approximate % funding
Pharmaceutical companies
Charities
Government bodyBundesministerium für Gesundheit70
Research councils
EU funding scheme
OtherBundesinstitut für Arzneimittel und Medizinprodukte (BfArM)30
5. Contact details for enquiries
Scientific Enquiries
Title Dr
Last name Weber-Schoendorfer
First name Corinna
Address line 1Pharmakovigilanzzentrum Embryonaltoxikologie
Address line 2Augustenburger Platz 1 
Address line 3 
CityBerlin 
Postcode13353 
CountryGermany
Phone number (incl. country code)49-30-450525711 
Alternative phone number49-30-450525702 
Fax number (incl. country code)49-30-450525902 
Email address corinna.weber-schoendorfer@charite.de
Public Enquiries
Title Professor 
Last name Schaefer 
First name Christof 
Address line 1Pharmakovigilanzzentrum Embryonaltoxikologie 
Address line 2Augustenburger Platz 1 
Address line 3 
City13353 
PostcodeBerlin 
CountryGermany 
Phone number (incl. country code)49-30-450525701 
Alternative phone number49-30-450525702 
Fax number (incl. country code)49-30-450525902 
Email address christof.schaefer@charite.de 
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