TNF ALPHA INHIBITOR USE AFFECTS BIRTHWEIGHT INDEPENDENTLY OF THE SOLUBLE FMS-LIKE TYROSINE KINASE 1 / PLACENTAL GROWTH FACTOR RATIO IN PREGNANT WOMEN WITH RHEUMATOID

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Objective: The use of tumor necrosis factor ↑ (TNF↑) inhibitors in pregnant women with rheumatoid arthritis (RA) improves birthweight, while in women with preeclampsia high levels of soluble fms-like tyrosine kinase 1 (sFlt-1) result in a reduction in birthweight, possibly because binding of placental growth factor (PlGF) to sFlt-1 reduces its activity. Here we studied whether the beneficial effect of TNF↑ inhibitors on birthweight involves a reduction in sFlt-1 and an improved sFlt-1/PlGF ratio. Design and method: Levels of sFlt-1 and PlGF were retrospectively determined in each trimester for 158 women enrolled in a prospective study on pregnancy and RA (Preconception Counseling in Active RA study) and treated according to a treatment protocol aimed at minimal disease activity. Results: Half (52.5%) of the women used TNF↑ inhibitors during (part of) their pregnancy. There was no significant difference in the levels of sFlt-1 and PlGF or their ratio between TNF↑ inhibitor users and non-users when comparing the biomarker values per trimester. Correction for parity, other drug use (sulfasalazine, prednisone, hydroxychloroquine), trimester, and disease activity score (DAS28CRP) did not alter this outcome. The well-known negative correlation between sFlt-1 and birthweight was observed in women not using TNF↑ inhibitors and became stronger in each subsequent trimester. Remarkably, this association was entirely absent in all trimesters in women using TNF↑ inhibitors. Conclusions: TNF↑ inhibitor use by pregnant women with RA does not alter the levels of sFlt-1 and PlGF or their ratio, although it did annihilate the negative correlation between sFlt-1 and birthweight. This indicates that TNF↑ inhibitor use improves birthweight independently of the sFlt-1/PlGF ratio.