AB0341\u2005SLE PREGNANCIES AT HIGH RISK FOR PRE-ECLAMPSIA BENEFIT MOST FROM COMBINATION OF LOW DOSE ASPIRIN AND HYDROXYCHLOROQUINE

Abstract

Women with SLE face a high risk of preeclampsia (PE). Low dose Aspirin (LDA) is known to protect against PE in non-autoimmune patients and is recommended for SLE patients1. Besides, a beneficial effect of hydroxychloroquine (HCQ) on the occurrence of PE has recently been discussed2.To investigate the influence of LDA and HCQ on the occurrence of PE in SLE patients.Pregnancies of women with SLE from an outpatient pregnancy clinic were prospectively evaluated. Clinical characteristics, medication use and pregnancy outcomes were analysed. Association of LDA use (latest from gestational week 16 on) and HCQ use (from 1st trimester on) with PE were analysed using a multiple logistic regression model (adjustment for age, BMI, hypertension, disease activity in 1st trimester, lupus nephritis, nulliparity, history of PE and high-risk aPL profile3).We enrolled 190 lupus pregnancies (148 women, 1995-2019). Additional risk factors for PE were present in 83.7%: 55.8% showed a high-risk profile (HRP) for PE according to ACOG4 (history of PE, hypertension, lupus nephritis or aPL), another 27.9% had at least one moderate risk factor (nulliparous, BMI>30 or age>35) (see table 1).Each 20.5% of pregnancies received HCQ only or LDA only, while 22.6% were prescribed both drugs. 36.3% took neither HCQ nor LDA. Women with HRP were more likely to take LDA alone or in combination with HCQ (28.3% and 35.8%, respectively).PE occurred in 13.2% of pregnancies (7.7% in HCQ only, 15.4% in LDA only, 14.0% in HCQ and LDA, 14.5% in no HCQ or LDA). Most pregnancies affected by PE carried a HRP (88.0%).Use of LDA was significantly associated with a lower risk for PE [aOR 0.21 (95%-CI 0.05-0.99), p<0.05]. HCQ use also had a moderating effect on the incidence of PE, but this effect did not reach significance [aOR 0.47 (95%-CI 0.15-1.52), p=0.21]. If only pregnancies with HRP were considered, the effect size increased for HCQ (LDA [aOR 0.18 (95%-CI 0.04-0.96), p<0.05], HCQ [aOR 0.28 (95%-CI 0.07-1.14), p=0.075]).In this prospective real-life cohort, timely LDA medication was associated with a lower risk of PE in SLE pregnancies. In a multiple regression model taking LDA and HCQ into account, the favourable effect on the occurrence of PE was partially explained by HCQ. In particular, SLE patients at high risk for PE seem to benefit from HCQ during pregnancy. Future research may reveal mechanisms by which HCQ might lower the incidence of PE.[1]doi: 10.1136/annrheumdis-2016-209770[2]doi: 10.1111/bcp.14131[3]doi: 10.1136/annrheumdis-2019-215213[4]doi: 10.1097/AOG.0000000000002708Table 1.Patient characteristics and risk profileHCQ only (n=39)LDA only (n=39)HCQ + LDA (n=43)no HCQor LDA(n=69)Patient characteriticsAge (years), median (IQR)29 (25-33)32 (30-33)30 (28.5-33.5)31 (28-35)BMI, median (IQR)23.5 (22-25)23 (22-24)22 (22-24)23 (22-24)Chronic Hypertension, n (%)7 (17.9%)9 (23.1%)6 (14.0%)9 (13.0%)Preconception counselling, n (%)23 (59.0%)28 (71.8%)35 (81.4%)41 (59.4 %)Obstetrical historyNulliparous, n (%)20 (51.3%)26 (66.7%)33 (76.7%)36 (52.2%)Previous fetal loss, n (%)1 (2.6%)10 (25.6%)14 (32.6%)10 (14.5%)Previous PE, n (%)2 (5.1%)4 (10.3%)4 (9.3%)5 (7.2%)SLE characteristicsand therapyDisease duration (years), median (IQR)7.0 (2.0-11.0)7.5 (3.0-11.5)6.7 (3.4-10.0)6.0 (3.0-9.2)SLEDAI, median (IQR)2.0 (1.0-4.3)2.0 (0-2.5)4.0 (2.0-4.0)2.0 (0-4.0)Lupus nephritis, n (%)9 (23.1%)13 (33.3%)18 (41.9%)14 (20.3%)Anti-dsDNA antibodies, n (%)22 (56.4%)15 (38.5%)36 (83.7%)33 (47.8%)Prednisolone therapy, n (%)26 (66.7%)15 (38.5%)25 (58.1%)29 (42.0%)Prednisolone (mg/d), median (IQR)5.0 (5.0-8.0)5.0 (5.0-7.5)5.0 (4.0-5.0)5.0 (5.0-8.0)aPL statusAPS, n (%)-12 (30.8%)14 (32.6%)2 (2.9%)Any positive aPL, n (%)-20 (51.3%)19 (44.2%)5 (7.2%)LAC, n (%)-15 (38.5%)13 (30.2%)3 (4.3%)ACL, n (%)-14 (35.9%)13 (30.2%)4 (5.8%)β2-GP1, n (%)-12 (30.8%)12 (27.9%)2 (2.9%)LAC = Lupus anticoagulant, ACL = Anticardiolipin antibody, β2-GP1 = β2-Glycoprotein I antibodyNone declared