The sFlt-1 to PlGF ratio in pregnant women with rheumatoid arthritis: impact of disease activity and sulfasalazine use

Abstract

Objectives An elevated sFlt-1/PlGF-ratio has been validated as a significant predictor of preeclampsia, but has not been established in women with rheumatoid arthritis (RA). We explored whether the sFlt-1/PlGF-ratio could be altered due to disease activity in RA, and could be applied in this population to predict preeclampsia. Since sulfasalazine has been suggested to improve the angiogenic imbalance in preeclampsia, we also aimed to examine whether sulfasalazine could affect sFlt-1 or PlGF levels. Methods Making use of a nationwide, observational, prospective cohort study on pregnant women with RA, sFlt-1 and PlGF were measured in the third trimester. A total of 221 women, aged 21–42 years, were included, with a median gestational age of 30 + 3 weeks. Results No differences in sFlt-1 or PlGF were observed between women with high, intermediate or low disease activity (p= 0.07 and p= 0.41), whereas sFlt-1 and PlGF did not correlate with DAS28-CRP score (r=-0.01 and r=-0.05, respectively). Four (2%) women with a sFlt-1/PlGF-ratio ≤38 developed preeclampsia in comparison to three (43%) women with a ratio > 38, corresponding to a negative predictive value of 98.1%. Sulfasalazine users (n = 57) did not show altered levels of sFlt-1 or PlGF in comparison to non-sulfasalazine users (n = 164, p= 0.91 and p= 0.11). 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 ≤38 can be used to exclude preeclampsia. Additionally, sulfasalazine use did not affect sFlt-1 or PlGF levels in this population.

Angiogenic imbalance in pre‐eclampsia and fetal growth restriction: enhanced soluble fms‐like tyrosine kinase‐1 binding or diminished production of placental growth factor?

“…Our study has implications for the treatment of PE with or without FGR. Until now, research has focused on ways of reducing sFlt-1, by using drugs that have been shown to lower placental sFlt-1 release in vitro 22,23 , suppressing placental sFlt-1 production with short-interfering RNA 24 or removing excess sFlt-1 through apheresis [25][26][27][28] . The concept behind these approaches is that reducing sFlt-1 will normalize the level of free circulating PlGF.…”

Omeprazole Administration in Preterm Preeclampsia: a Randomized Controlled Trial to Study Its Effect on sFlt-1 (Soluble Fms-Like Tyrosine Kinase-1), PlGF (Placental Growth Factor), and ET-1 (Endothelin-1)

“…Remarkably, this pattern has also been witnessed with other drugs such as pravastatin or sulfasalazine, which have shown significant sFlt-1-lowering properties in both placental tissues and animal models, although these actions were not apparent when examined in human patients. [16][17][18][19][20] One possibility is that the doses applied in experimental models were much higher compared to the concentrations administered in clinical studies. Indeed, when the C max equivalent of 40 mg esomeprazole (5 µmol/L) was applied in primary tissues, it did not induce a significant reduction in sFlt-1, in contrast with concentrations of 50 or 100 µmol/L.…”

Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia

“…PlGF and sFlt-1 levels are elevated in both the serum and synovial fluid in RA, and their levels in synovial fluid correlate with disease activity [ 84 ]. According to a study by Neuman et al, the sFlt1/PlGF ratio is not influenced by disease activity in pregnant women with RA, and a cut-off ≤38 can be used to rule out pre-eclampsia [ 87 ].…”