POS0542 DISEASE ACTIVITY IN PREGNANT WOMEN WITH RHEUMATOID ARTHRITIS: IMPACT ON THE SOLUBLE FMS-LIKE TYROSINE KINASE-1 TO PLACENTAL GROWTH FACTOR RATIO
Authors: H. T. Smeele, R. I. Neuman, A. H. J. Danser, R. Dolhain, W. Visser
Journal: Annals of the Rheumatic Diseases (2021)

Background: An elevated sFlt-1 indicates soluble Fms-like tyrosine kinase-1 (sFlt-1)/ placental growth factor (PlGF) ratio has recently been validated as significant predictor of preeclampsia (PE)(1). However, raised sFlt-1 levels due to inflammation are observed in patients with rheumatoid arthritis (RA)(2). The use of the sFlt-1/PlGF ratio for the prediction of PE has not been evaluated in pregnant women with diseases that are characterized by high levels of inflammation, such as RA Objectives: We investigated whether sFlt-1 and/or PlGF are altered in pregnant women with RA according to disease activity, and evaluated whether a sFlt-1/PlGF ratio of ≤38 could be used to predict the absence of PE in pregnant RA-patients. Methods: This study was embedded in a nationwide, observational, prospective cohort study on pregnant women with RA (PARA-study). sFlt-1 and PlGF levels were measured, using automated analyzer (Cobas-6000, e-module; Roche-Diagnostics), in the third trimester of pregnancy. Results: A total of 221 women, aged 21–42 years, were included. Values of sFlt-1, PlGF and sFlt-1/PlGF ratio were not significantly correlated with the DAS28-CRP (Figure 1). CRP correlated weakly with PlGF (r=-0.14, p=0.03), while no correlation was found with sFlt-1 or the sFlt-1/PlGF ratio. Preeclampsia occurred in four out of 214 women with a ratio ≤38 (2%) in contrast to three out of seven women with a ratio &gt;38 (43%), p&lt;0.001 (Table 1). When stratified to a sFlt-1/PlGF ratio of ≤38 only 2% of women developed preeclampsia, compared to 43% of the women with a ratio &gt;38. The observed sensitivity and specificity for a sFlt-1/PlGF ratio cut-off of ≤38 were 42.1% and 98.1%, respectively, with a negative predictive value (NPV) of 98%. All women that developed PE, developed PE &gt;4 weeks after collecting of blood samples in the 3rd trimester, therefore the observed NPV could be even higher. Table 1. Pregnancy Outcome according to sFlt-1/PlGF ratio with a cut-off value of 38. Parameter Ratio ≤38 Ratio &gt;38 P-value N 214 7 GA at birth, weeks 39 (38 - 40) 37 (36 - 40) 0.05 &lt;34 2 (1) 0(0) 1.00 34 - 37 18 (8) 2 (29) 0.12 Male, n (%) 113 (53) 5 (71) 0.45 Birth weight, grams 3420 (2998 - 3800) 2620 (2360 - 2850) &lt;0.01 Maternal Outcome Gestational Hypertension 15 (7) 2 (29) 0.09 Preeclampsia 4 (2) 3 (43) &lt;0.001 Time to delivery, days 66 (52 - 75) 52 (44 - 66) 0.08 Fetal Outcome Birth weight percentile &lt;10 33 (15) 5 (71) &lt;0.01 Fetal/Neonatal Death 1 (1) 0 (0) 1.00 Data are reported as median (interquartile range) or number (percentage). sFlt-1 indicates soluble Fms-like tyrosine kinase-1; PlGF, placental growth factor; GA, gestational age. Time to delivery is defined as the amount of days between blood sampling and delivery. Conclusion: Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity, and a cut-off of ≤38 of this ratio can be used to exclude preeclampsia. References: [1]H. Zeisler et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N Engl J Med 2016; 374: 13-22. DOI 10.1056/NEJMoa1414838. [2]S. Ballara et al. Paleolog. Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum 2001; 44 : 2055-2064. DOI 10.1002/1529-0131(200109)44:9&lt;2055::AID-ART355&gt;3.0.CO;2-2. Figure 1. Correlations between sFlt-1, PlGF and sFlt-1/PlGF ratio with DAS28-CRP and CRP. Correlation coefficients for sFlt-1 (A-B), PlGF (C-D) and sFlt-1/PlGF ratio (E-F) with DAS28-CRP and CRP. Acknowledgements: The kits for measurement of sFlt-1/PlGF ratio were a kind gift from Roche Diagnostics, Germany. We thank all participants of the PARA study. Additionally, we extend our gratitude to the laboratory workers, in particular Nadine Davelaar and Priyanka Bangoer, and research assistants for their contribution to the data collection. We thank ReumaNederland (LLP project number: LLP-26) for their financial support. Disclosure of Interests: Hieronymus TW Smeele: None declared, R.I. Neuman: None declared, A.H.J. Danser: None declared, Radboud Dolhain Speakers bureau: Yes UCB, Roche, Abbvie, Genzyme, Novartis, Consultant of: Yes, Galapagos, Grant/research support from: Yes, UCB, W. Visser: None declared