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Background:Treatment of systemic lupus erythematosus (SLE) is tailored according to the intensity of SLE disease activity and aims to achieve remission. Current definitions of remission and disease activity categories are mostly based on the SLE Disease Activity Index (SLEDAI), which has important limitations. The SLE Disease Activity Score (SLE-DAS) is a validated continuous disease activity score with higher accuracy in measuring SLE activity and higher sensitivity-to-change as compared to SLEDAI1. SLE-DAS is user-friendly with its online calculator.Objectives:To derive and validate the SLE-DAS cut-off values for defining SLE disease activity categories and SLE clinical remission state.Methods:Derivation study was conducted at the Padova Lupus Clinic. Validation was performed prospectively in patients from the Cochin Lupus Clinic and by post-hoc analysis of BLISS-76 (NCT00410384) trial. Gold-standard for clinical remission state was fulfillment of Definition Of Remission In SLE (DORIS). In Padova and Cochin Clinics, at time of inclusion, a senior clinician classified each patient as presenting: (i) remission, (ii) mild, or (iii) moderate/severe disease activity. Derivation of the SLE-DAS cut-offs for disease activity categories was performed using ROC curve analysis against this expert clinical classification. Performance of these SLE-DAS categories of disease activity was assessed as compared with: (i) expert classification (in Cochin cohort); (ii) British Isles Lupus Assessment Group (BILAG) index (in BLISS-76). An index-based and a Boolean definition of remission were tested applying decision trees, using CHAID (chi-square automatic interaction detection) algorithm and their performance estimated.Results:We included 1190 SLE patients (221 in Padova, 150 in Cochin and 819 from BLISS-76 cohorts). In the derivation cohort, best SLE-DAS cut-off values for disease activity categories were: (i) remission, SLE-DAS≤2.08; (ii) mild activity, 2.087.10. Table 1 shows the performance of these SLE-DAS cut-offs. The SLE-DAS Boolean-based definition of remission (all SLE-DAS clinical items scores = 0 and prednisone ≤5mg/day) showed sensitivity and specificity of 100% in the derivation (Padova) and validation (Cochin) clinical cohorts. The SLE-DAS index-based definition of remission (SLE-DAS ≤2.08 and prednisone ≤5mg/day) presented sensitivity =100% and specificity =97.4% in the derivation and validation clinical cohorts. The SLE-DAS definitions of remission were fully substantiated by CHAID.Table 1.Performance of SLE-DAS cut-offs for remission and disease activity categories compared to physician’s classification and BILAG (n =1190).Disease activity categorySensitivity (%)Specificity (%)Accuracy (%)DerivationPadova CohortRemission(SLE-DAS≤2.08)99.397.198.6Mild Disease Activity(2.0874.298.995.5Moderate and Severe Disease Activity(SLE-DAS>7.10)97.496.796.8ValidationCochin CohortRemission(SLE-DAS≤2.08)99.193.998.0Mild Disease Activity(2.0882.699.296.7Moderate and Severe Disease Activity(SLE-DAS>7.10)100.098.698.7ValidationBLISS-76Remission and Mild Disease Activity§vs. Moderate and Severe Disease Activity§§ (SLE-DAS≤7.10 vs. >7.10)91.484.190.8§ Remission/Mild: No BILAG B or A scores§§ Moderate/severe: ≥1 BILAG B or A scoresConclusion:The SLE-DAS is an accurate and easy to use tool for defining clinical remission state and SLE disease activity categories, validated with both the expert assessment and BILAG.References:[1]Jesus D, et al. Derivation and validation of the SLE Disease Activity Score (SLE-DAS): a new SLE continuous measure with high sensitivity for changes in disease activity. Ann Rheum Dis 2019;78:365-71.Acknowledgements:The authors would like to thank GlaxoSmithKline (Uxbridge, UK) for granting access to the data from the BLISS-76 trial through the Clinical Study Data Request consortium.Disclosure of Interests:None declared

Background:Active Systemic Lupus Erythematosus (SLE) during pregnancy is associated with poor obstetrical outcome but it is still not clear if remission, lupus low disease activity state (LLDAS) is the best target to achieve at conception. Besides, the effect of damage on pregnancy outcome has not been studied.Objectives:Our aim was to determine the 1st trimester risk factors for adverse pregnancy outcome (APO).Methods:Inclusion criteria were: 1) women≥18 years enrolled in the prospective GR2 study; 2) with SLE (SLICC criteria); 3) and an ongoing singleton pregnancy at 12 weeks (only 1 pregnancy per patient). We used the following definitions: DORIS1, DORIA2, clinical SLEDAI-2K=0, LLDAS3 (for SLE activity), SFI4 (for flares), and SLICC-damage index5 (for damage). APO included: foetal death, neonatal death, placental insufficiency with premature deliveryrd percentile).Results:238 patients were included. 234 (98.3%) women were on hydroxychloroquine (HCQ) and 206 (86.5%) had a clinical SLEDAI-2K=0. Regarding pregnancy outcome, 230 (96.6%) patients had a live birth (mean term 37.7 weeks). Thirty-four (14.3%) patients developed at least 1 APO: placental insufficiency (n=22), foetal death (n=7), neonatal death (n=1), and SGA (n=5). Two different regression logistic models were assessed, one for DORIA and one for LLDAS. We found that only SLICC-Damage index and lupus anticoagulant (LAC) were associated with APO (p=0.02, OR 1.8, 95% CI: 1.1-2.9; p=0.001, OR 4.2, 95% CI: 1.8-9.7 respectively for DORIA model; p=0.03, OR 1.7, 95% CI:1.1-2.8; p=0.002, OR 3.7, 95% CI: 1.6-8.7 respectively for LLDAS model).Conclusion:We confirmed that LAC predicts APO. We found for the first time that chronic damage at 1st trimester also predicted APO. No effect of remission/LLDAS was observed in this cohort of patients on HCQ with a stable and well-controlled SLE.References:[1]van Vollenhoven R, et al. ARD 2017.[2]Zen M, et al. ARD. 2015.[3]Franklyn, K. et al. ARD 2016.[4]Petri M, et al. NEJM 2005.[5]Gladman DD, et al. Arthritis Rheum, 1997.Table 1.Univariate analysis for APOMaternal featuresTotal (N=238)APO (N=34)Non-APO (N=204)P valueAge, mean (SD)31.6(4.5)30.7(4.8)31.7(4.4)0.22Secondary APS34(14.3)10(29.4)24(11.8)0.01Previous renal phenotype67(28.2)13(38.2)54(26.5)0.16At least 1 flare during pregnancy37(15.5)6(17.4)31(15.2)0.80Positive anti-DNA (N=222)104(46.8)21(67.7)83(43.5)0.01Hypocomplementemia (N=216)57(26.4)13(40.6)44(23.9)0.05LAC (N=232)41(17.7)15(44.1)26(13.1)Triple aPL (N=232)17(7.3)5(14.7)12(6.1)0.0824h-proteinuria>0.5g/day9(3.8)3(8.8)6(2.9)0.12Activity/DamageSLEDAI-2K, median (IQR) (N=212)2(0-3)2(2-4)2(0-2)0.01SLICC-DI, median (IQR) (N=236)0(0-0)0(0-0)0(0-0)0.007PGA, median (IQR)(N=235)0.1(0-0.2)0.1(0-0.41)0.1(0-0.2)0.06DORIA remission*154(64.7)17(50.0)137(67.2)0.05DORIS remission**147(61.8)17(50.0)130(63.4)0.13LLDAS (N=219)157(71.7)19(57.6)138(74.2)0.05Clinical SLEDAI-2K=0206(86.5)28(82.4)178(87.3)0.44TreatmentPrednisone (PDN)119(50.0)23(67.7)96(47.1)0.03PDN (mg/day) median (IQR)7(5-10)0(0-6)5(0-10)0.007Immunosuppressants57(24.0)13(38.2)44(21.6)0.04Hydroxychloroquine234(98.3)34(100.0)200(98.0)1.00Low dose aspirin165(69.3)29(85.3)136(66.7)0.03Low molecular weight heparin61(25.6)15(44.1)46(22.6)0.01Legend: APS: antiphospholipid syndrome; aPL: antiphospholipid; PGA: Physician global assessment. *: DORIA definition of remission = clinical SLEDAI=0 and prednisone ≤5 mg/day; **: DORIS definition of remission = clinical SLEDAI=0, prednisone ≤5 mg/day, and PGADisclosure of Interests:None declared.

Background:Whether and when immunosuppressive therapy may be safely withdrawn in patients with lupus nephritis (LN) is still poorly defined. Indeed, there is no clear agreement about the optimal duration of maintenance treatment.Objectives:We aimed at assessing the rate and predictors of flare after IS withdrawal in patients with LN in remission.Methods:Patients with systemic lupus erythematosus (SLE) (ACR criteria) and biopsy-proven LN diagnosed between 1990 and 2019, ever treated with IS and currently in follow-up were considered. IS discontinuation was defined as the complete withdrawal of any immunosuppressive drug in patients in remission. Remission was defined as normal serum creatinine, proteinuria 0.5 g/24h requiring an increase in corticosteroid therapy or the reintroduction of IS. Predictors of a subsequent flare were analyzed by multivariate logistic regression analysis.Results:Out of 456 SLE patients regularly followed-up, 206 (45.1%) had LN and were considered in our study. Eighty-three patients (40.3%) discontinued IS after remission achievement (Table 1). After stopping therapy, patients were followed for a mean±SD of 99±77 months (range 12-378). Nineteen patients (22.8%) developed a flare after IS discontinuation, after a mean±SD follow-up of 78±68 months (range 7-312), and were re-treated; among them, 6 patients (7.2%) experienced a renal and 13 (15.6%) an extra-renal flare. Compared to patients who flared, patients in persistent IS-free remission had longer remission before IS withdrawal (51.2±31.5 vs. 29.3±16.5 months, pTable 1.Characteristics of 83 patients with LN in remission who discontinued immunosuppressive therapy, overall and according to flare occurrenceTotal patients (83)Patients with flare (19)Patients without flare (64)P valueFemale, N(%)72 (88.7)16 (84.2)56 (87.5)nsAge at 2019, years43±1139±11.545±10.40.049SLE duration at 2019, years18±916.7±9.018.6±8.6nsSLE duration at IS discontinuation, years9.7±7.67.1±6.110.5±7.8nsTime to achieve remission, months27±3722.1±35.628.5±37.6nsRemission duration at IS discontinuation, months46±3029 ±16.551±31.5IS therapy duration, years6.7±4.35.2±3.87.1±4.20.061Anti dsDNA, N(%)65 (78.3)18 (95)47 (73)0.059HCQ after IS discontinuation, N(%)67 (80.7)12 (63.1)55 (85.9)0.005IS, immunosuppressant; HCQ, hydroxychloroquineTable 2.Multivariate logistic regression: predictors of flare occurrenceDependent variable: flare occurrenceOR95% CIp valueNumber of ISs, ever3.2641.030-10.3420.044HCQ therapy after IS discontinuation0.0960.014-0.6520.017Remission duration at IS discontinuation0.9540.912-0.9970.037Cyclophosphamide, ever0.0650.008-0.5480.012IS, immunosuppressant; HCQ, hydroxychloroquineConclusion:Based on our experience, withdrawal of IS is feasible in selected patients with LN, i.e. patients who achieved stable remission and received maintenance therapy with antimalarials. Patients who experience new flares can re-achieve remission with an appropriate treatment.Disclosure of Interests: :Margherita Zen Speakers bureau: BMS, Ely Lilly, Janssen, GSK, Mariele Gatto Speakers bureau: GSK, Francesco Benvenuti: None declared, Francesca Saccon: None declared, Maddalena Larosa: None declared, Luca Iaccarino Speakers bureau: GSK, Pfizer, Janssen, Novartis, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS

Background:One of the 3 features of obstetrical antiphospholipid syndrome (APS) is severe preeclampsia (PE). Its time of occurrence, the associated risk of thromboses and systemic lupus erythematosus (SLE) have not been reported yet.Objectives:We analyzed severe PE in a series of women with APS.Methods:We retrospectively collected data of female patients from 5 French internal medicine and 1 Italian rheumatology units. Inclusion criteria were: a severe PE/eclampsia(1), that occurred before 34 weeks of gestation (WG) in patients who met the APS classification criteria(2).Results:40 patients were enrolled (Table 1). Because of known APS/positive aPL/previous obstetrical complications, 23(57.5%) patients were treated during the index PE: 4 with low dose aspirin (LDA), 4 with low molecular weight heparin (LMWH), and 15 with a combination of both. 7 patients were also treated with hydroxychloroquine, 8 with corticosteroids and 3 with immunosuppressants. 17(42.5%) patients received no treatment. 24(60%) live births were observed. During a follow-up period of 3 years, 26(65%) patients had at least 1 new pregnancy, with a total of 38 pregnancies which resulted in 33(86.8%) live births. 57.5% pregnancies who resulted in live births occurred without any maternal or fetal complications. All 26 patients who had at least 1 pregnancy after index PE were treated with LDA; LMWH was given at prophylactic and therapeutic dosage in 13(50%) patients, respectively. No patient experienced 3 consecutive miscarriages.Table 1.40 APS patients with severe PEOverall features (n, %)Patients40 (100)Age at PE, (median, IQR)30.5 (27-33)PE term, WG (median, IQR)25.5 (23-29) Live births24 (60) Birth term, WG (median, IQR)25.5 (23.7-30.3) Associated SLE12 (30)Maternal complications (n, %)25 (62.5) HELLP18 (45) E6 (15) CAPS3 (7.5) Placental abruptions3 (7.5)Fetal complications (n, %)31 (77.5) IUGR18 (45) IUFD11 (2.5) Preterm delivery22 (55)Obstetrical history (n, %) Primiparous21 (52.5) Index PE before APS12 (30)Thrombosis (n, %) Thrombosis before PE index14 (35.0) Thrombosis after PE index2 (5.0)Abs at APS diagnosis (n, %) aPL triple positivity21 (52.5) IgG/IgM anti-cardiolipin34 (85.0) IgG/IgM anti-β2GPI25 (62.5) LAC33 (82.5)Legend to Table 1:PE: preeclampsia; APS: antiphospholipid syndrome; IQR: interquartile range; WG: weeks of gestation; SLE: systemic lupus erythematosus; HELLP: Hemolysis, elevated liver enzymes, low platelet; E: eclampsia; CAPS: catastrophic APS; IUGR: intrauterine growth restriction; IUFD: intrauterine fetal death; CHB: congenital atrioventricular block; aPL: antiphospholipid antibodies; LAC: lupus anticoagulant.Conclusion:Among the APS criteria, “3 consecutive miscarriages criterion” was not found. The majority of patients also experienced thrombosis and SLE before the index PE.References:[1]Diagnosis and Management of preeclampsia and eclampsia. International Journal of Gynecology &Obestetrics 2002;77:67-75.[2]Miyakis S, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295e 306.Disclosure of Interests:Maddalena Larosa: None declared, Nathalie Morel: None declared, Meriem BELHOCINE: None declared, Amelia Ruffatti: None declared, Nicolas Martin Silva: None declared, Romain Paul: None declared, Luc Mouthon: None declared, Michel DREYFUS: None declared, Jean-Charles PIETTE: None declared, Odile Souchaud-Debouverie: None declared, Catherine Deneux-Tharaux: None declared, Vassilis Tsatsaris: None declared, Emmanuelle Pannier: None declared, Gaêlle Guettrot Imbert: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Nathalie Costedoat-Chalumeau Grant/research support from: UCB to my institution