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\begin{document}

\title{Reported congenital malformations after exposure to non-tumour necrosis
factor inhibitors: a retrospective comparative study in EudraVigilance}



\author[1]{Nafise Ghalandari}%
\author[2]{Ineke Crijns}%
\author[3]{Jorieke Bergman}%
\author[1]{Radboud Dolhain}%
\author[4]{Eugène van Puijenbroek}%
\author[1]{Mieke Hazes}%
\affil[1]{Erasmus Medical Center}%
\affil[2]{Medicines Evaluation Board}%
\affil[3]{University of Groningen}%
\affil[4]{Lareb}%


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  \date{May 25, 2024}


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\begin{abstract}
Aim To evaluate the number and nature of reported congenital
malformations (CMs) after intrauterine exposure to non-tumour necrosis
factor inhibitors (non-TNFis) compared to certolizumab pegol (CZP)
Material and methods A retrospective comparative study was conducted in
the EudraVigilance (EV) database. EV is a pharmacovigilance database,
which can be used for detecting safety signals and generating hypotheses
on possible relations between drugs and adverse events. A supposedly
safe biologic (CZP) was considered as the reference group.
Pregnancy-reports of non-TNFis and CZP were extracted. Odds ratios (ORs)
for CMs were calculated for each non-TNFi, versus CZP (quantitative
assessment). Then, CM patterns were compared to CZP in consultation with
a clinical geneticist (qualitative assessment). Results ORs were not
statistically significant except for belimumab and vedolizumab (similar
in magnitude). Although qualitative analyses did not show any specific
patterns for belimumab but three cases of corpus callosum agenesis (CCA)
were identified for vedolizumab (versus null in CZP and other
investigated non-TNFis). Two of the CCA cases were associated with other
neurological CMs (one cerebral ventriculomegaly with microcephaly and
one polymicrogyria). This may indicate that these CCAs are related to
undiagnosed genetic alterations or are associated with the underlying
maternal disease, although a definite relationship with vedolizumab
exposure cannot be ruled out. Conclusion No special safety signal was
identified regarding the occurrence of CMs after exposure to non-TNFis,
except for vedolizumab. Based on available information, no firm
conclusions can be made regarding observed CCAs in the vedolizumab group
(it warrants further research)%
\end{abstract}%



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