0477: Continuing TNFi After Pregnancy Diagnosis in Women with Chronic Rheumatic Inflammatory Diseases Is Not Associated with Worse Obstetrical or Infant Outcomes and Seems to Reduce Risk of Maternal Severe Infection: The Results of the Emulated Target Trial BioGRIC

Anna Molto¹, aya ajrouche², Diep Tran², Nathalie Costedoat-Chalumeau³, Elisabeth Elefant⁴, Vassilis Tsatsaris⁵, Jeanne Fresson⁶, Brigitte Bader-Meunier⁵, Bruno Fautrel⁷ and Florence Tubach², ¹HOPITAL COCHIN AP-HP, Service de Rhumatologie, Paris, France, ²Centre de pharmaco-épidémiologie de l'APHP, Paris, France, ³Inserm DR Paris 5, Paris, France, ⁴APHP, Paris, France, ⁵Paris-Cité University, Paris, France, ⁶CHU Nancy, Nancy, France, ⁷Sorbonne Université APHP, Paris, France

Background/Purpose: Many women with chronic rheumatic inflammatory diseases (CRID) stop tumor necrosis factor inhibitors (TNFi) treatment once pregnancy is confirmed to avoid potential adverse fetal events but taking the risk of inflammatory flare.

The aim of the study was to compare in real life settings the pregnancy outcomes of two treatment strategies among women with CRID: to continue TNFi vs. stop TNFi upon pregnancy diagnosis.

Methods: the French nationwide health insurance database (Système National des Données de Santé) was used to emulate a target trial in adult women, with CRID (i.e., rheumatoid arthritis, psoriatic arthritis or spondyloarthritis), having started a singleton pregnancy between 2008 and 2017, and and being treated with TNFi upon pregnancy diagnosis. We compared the frequency of unfavorable pregnancy outcomes (malformations, obstetrical complications, and infections) between the treatment strategies at pregnancy diagnosis, using inverse probability weighted marginal models.

Results: A total of 2082 singleton pregnancies of CRID women (579 RA and 1503 SpA) exposed to TNFi 6 weeks after last menstrual period were identified; among them, in 1497 (72%) TNFi was discontinued.

Mean (SD) age of women at the start of pregnancy was 31 (5) years and mean (SD) disease duration was 4 (5) years. Continuation of TNFi was not associated with increased frequencies of unfavorable obstetrical nor infant outcomes, and interestingly, the proportion of maternal severe infections (i.e., requiring hospitalization) was significantly lower in the ‘continue’ group (1(0.2%) vs. 19 (1.3%), with an adjusted risk ratio = 0.2 [0.1 - 0.6]).

	Outcomes	TNFi continue   (n = 584)$	TNFi stop (n=1497)$	Relative Risk              (Continue vs. Stop) 95% CI
Obstetrical	Live births	505 ( 86.6%)	1327 ( 88.6%)	0.9 [0.9 - 1.0]
	Spontaneous abortion (GA < 22 WG or birth weight < 500g)	11 (  1.9%)	50 (  3.3%)	0.6 [0.3 - 1.2]
	Intrauterine fetal death (GA >=22 WG or birth weight >=500g)	6 (  1.1%)	8 (  0.5%)	2.0 [0.8- 5.3]
	Medical termination of pregnancy	4 (  0.6%)	15 (  1.0%)	0.6 [0.2 - 2.4]
	Preterm birth (GA between 22 and 37 among live birth)	37 (  6.4%)	108 (  7.2%)	0.9 [0.6 - 1.3]
	Small for GA ( < 10th percentile)	52 (  8.9%)	139 (  9.3%)	0.9 [0.7 - 1.4]
	Cesarean delivery	115 ( 19.8%)	337 ( 22.5%)	0.9 [0.7- 1.1]
	Eclampsia/Pre-eclampsia	6 (  1.0%)	21 (  1.4%)	0.7 [0.3 - 1.6]
	Extra-uterine pregnancy	0 (  0.0%)	5 (  0.3%)	-
Maternal	Hospital admission for infection (during pregnancy and 6 weeks post-delivery )	1 (  0.2%)	19 (  1.3%)	0.2 [0.1 - 0.6]
	Gestational diabetes	59 ( 10.2%)	155 ( 10.3%)	0.9 [0.7 - 1.4]
Infants	Major congenital malformation	12/486 (2.5%)	37/1293 (  2.9%)	0.9 [0.4 - 1.7]
	Severe infection (requiring hospitalization) during the first year of life	51/486 ( 10.6%)	119/1293 (  9.2%)	1.2 [0.8 - 1.7]
	NCIU admission for more than 48h in infants born after 37 WG	6/486 (  1.3%)	24/1293 (  1.9%)	0.7 [0.3 - 1.9]

$: Weighted pseudopopulation; Abbreviations: GA = gestational age; WG = weeks of gestation

Conclusion: In pregnant women with CRID treated with TNFi until pregnancy diagnosis, unfavorable obstetrical outcomes were not different to those observed when TNFi were maintained, and maternal severe infections were less frequent, when compared with a strategy of stopping TNFi.


A. Molto: None; a. ajrouche: None; D. Tran: None; N. Costedoat-Chalumeau: None; E. Elefant: None; V. Tsatsaris: None; J. Fresson: None; B. Bader-Meunier: None; B. Fautrel: AbbVie, 2, BMS, 2, Chugai, 2, Fresenius Kabi, 2, Galapagos, 2, Lilly, 2, Medac, 2, Nordic Pharma, 2, Novartis, 2, Pfizer, 2, Sobi, 2, UCB, 2; F. Tubach: Lundbeck, 2, Merck/MSD, 2, UCB, 2.