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Gender can influence incidence and clinical course of autoimmune diseases (ADs). Antiphospholipid syndrome (APS) is a rare AD characterised by thromboses and/or pregnancy morbidities and antiphospholipid antibodies (aPL) positivity. Our aim is to conduct a gender-oriented analysis of primary thrombotic APS (t-APS).Consecutive patients diagnosed with primary t-APS, followed from 1967 to 2019 in four European Centres, were enrolled.The cohort included 296 women and 137 men. Median age at onset [31 (24-46) vs. 41 (29-53) years, p0.001] was lower in females. In women, venous thromboses were more frequent while, among males, arterial events prevailed. During follow-up, 14% of patients suffered at least two relapses and this occurred especially among males (22% vs. 10%, p=0.001). No gender differences were found in the aPL profile (33% single, 24% double and 43% triple aPL positivity). Most patients had concomitant risk factors (RFs) for thrombosis: established cardiovascular RFs were represented especially among men while estrogenic exposure was the main RF in women.Women presented mostly with venous thromboses at a younger age, while men with arterial events, later in life and suffered more recurrent events. This different frequency of arterial and venous thromboses could be attributed mainly to the presence of additional RFs rather than to biological gender-specific issues. However, some RFs are exclusive or more represented in one gender rather than the other, so assessing the link of causality between gender and manifestations of t-APS remains difficult.

Background The rate of antiphospholipid antibody (aPL) negativization in antiphospholipid syndrome (APS) patients is uncertain, but it is estimated to be as high as 8%. Currently, a consensus definition of aPL negativization is lacking, as well as international recommendations on how to approach treatment in patients with a persistent aPL-negative seroconversion. Aim The aim of the Delphi survey was to evaluate the clinical approach and level of consensus among experts from the APS Study Group of the Italian Society for Rheumatology (SIR-APS) in different clinical scenarios. Methods Experts of SIR-APS were contacted using a survey methodology. Results A structured survey was circulated among 30 experts. Up to 90% of the interviewed experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart (90%). Almost full consensus exists among experts in some clinical settings, including: (1) the role of aPL negativization in the management of a thrombotic event determined by concomitant presence of cardiovascular risk factors, both modifiable and not modifiable (90%); (2) approach to young patients with triple aPL positivity who experienced pulmonary arterial thrombotic events and tested negative for aPL detection after 5 years of vitamin K antagonist (VKA) treatment (90%); (3) the use of “extra criteria” aPL antibody testing before pondering VKA suspension (93%). Conclusion A substantial agreement exists among experts on how to define aPL negativization. VKA suspension should be embraced with extreme caution, particularly in case of previous thrombotic events and/or triple aPL positivity. Nevertheless, VKA cessation might be considered when risk factors are carefully monitored/treated and the presence of “extra criteria” aPL is ruled out.

ObjectiveMultiple guidelines recommend continuing hydroxychloroquine (HCQ) for systemic lupus erythematosus (lupus) during pregnancy based on observational data. The goal of this individual patient data meta-analysis was to combine multiple datasets to compare pregnancy outcomes in women with lupus on and off HCQ.MethodsEligible studies included prospectively-collected pregnancies in women with lupus. After a manuscript search, 7 datasets were obtained. Pregnancy outcomes and lupus activity were compared for pregnancies with a visit in the first trimester in women who did or did not take HCQ throughout pregnancy. Birth defects were not systematically collected. This analysis was conducted in each dataset and results were aggregated to provide a pooled odds ratio.ResultsSeven cohorts provided 938 pregnancies in 804 women. After selecting one pregnancy per patient with a 1st trimester visit, 668 pregnancies were included; 63% took HCQ throughout pregnancy. Compared to pregnancies without HCQ, those with HCQ had lower rates of highly active lupus, but did not have different rates of fetal loss, preterm birth, or preeclampsia. Among women with low lupus activity, HCQ reduced the risk for preterm delivery.ConclusionThis large study of prospectively-collected lupus pregnancies demonstrates a decrease in SLE activity among woman who continue HCQ through pregnancy and no harm to pregnancy outcomes. Like all studies of HCQ in lupus pregnancy, this study is confounded by indication and non-adherence. As this study confirms the safety of HCQ and diminished SLE activity with use, it is consistent with current recommendations to continue HCQ throughout pregnancy.

Autoimmune diseases often affect young women and this may represent a problem in family planning. Pregnancies in these patients may carry several complications but nowadays the continued amelioration in treatment and management has greatly improved the pregnancy outcome. The main concern of these women obviously is the short- and long-term outcome of their children. A child born from a woman with autoimmune disease is potentially exposed in utero to maternal autoantibodies, cytokines, and drugs, and each item could impair his or her development. In addition, the maternal genetic heritage can favor autoimmunity. All these items could have a role, for example, in the development of autoimmune diseases (the same as the mother or different ones) or neurological disorders. Data in literature are controversial. This review will gather the available data possibly providing a useful tool for counseling future mothers.

The concern about the offspring’s health is one of the reasons for a reduced family size of women with rheumatic diseases (RD). Increased risk of autoimmune diseases (AD) and neurodevelopmental disorders (ND) has been reported in children born to patients with RD. Within a nationwide survey about reproductive issues of women with RD, we aimed at exploring the long-term outcome of their children. By surveying 398 patients who received their diagnosis of RD during childbearing age (before the age of 45), information about the offspring were obtained from 230 women who declared to have had children. A total of 148 (64.3%) patients were affected by connective tissue diseases (CTD) and 82 (35.7%) by chronic arthritis. Data on 299 children (156 males, 52.1%; mean age at the time of interview 17.1 ± 9.7 years) were collected. Twelve children (4.0%), who were born to patients with CTD in 75% of the cases, were affected by AD (8 cases of celiac disease). Eleven children had a certified diagnosis of ND (3.6%; 6 cases of learning disabilities); 9 of them were born to mothers with CTD (5 after maternal diagnosis). No association was found between ND and prenatal exposure to either maternal autoantibodies or anti-rheumatic drugs. Absolute numbers of offspring affected by AD and ND were low in a multicentre cohort of Italian women with RD. This information can be helpful for the counselling about reproductive issues, as the health outcomes of the offspring might not be an issue which discourage women with RD from having children.

Puerperium is a critical period for patients affected by autoimmune rheumatic diseases for the risk of disease's flares and difficulties in treating lactating mothers. We want to summarize the literature data about psychological and pharmacological management of these patients and possible risk factors of disease's flares.We made a narrative review on recent studies about puerperium in rheumatic autoimmune diseases patients.The physicians involved in management of patients during puerperium and in the follow-up of babies need to agree on maternal treatment because they need to reassure mothers about the safety of the prescribed medications. Furthermore, women with rheumatic diseases could present some musculoskeletal limitations and psychological problems, such as postpartum depression, which can lead to a sense of inadequacy to the mother's task. Families and physicians should be aware of these possible complications and support the new mothers providing correct counseling and practical help.

Background Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. Methods We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). Results We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p p p p Conclusions Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.

BACKGROUND The combination of low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH) until the end of gestation are the currently the accepted standard of care for the treatment of antiphospholipid-related obstetric disorders. In refractory cases, hydroxychloroquine (HCQ) can be added to this standard of care. OBJECTIVE To evaluate the haemostatic safety of LDA and LMWH (medium to high prophylactic doses) during pregnancy and the puerperium in women with both full-blown obstetric antiphospholipid syndrome (OAPS) (Sydney criteria) and noncriteria - incomplete - OAPS. STUDY DESIGN Retrospective/prospective multicentre observational study. Obstetric background, laboratory categories, delivery mode, antithrombotic regimens and bleeding complications were compared. SETTING A total of 30 tertiary European hospitals. PATIENTS Mainly, Caucasian/Arian pregnant women were included. Other ethnicities were minimally present. Women were controlled throughout pregnancy and puerperium. MAIN OUTCOME MEASURES The primary end-point was to evaluate the number of major and minor haemorrhagic complications in this cohort of women. Neuraxial anaesthetic bleeding complications were particularly assessed. Secondly, we aimed to compare local/general bleeding events between groups. RESULTS We studied 1650 women, of whom 1000 fulfilled the Sydney criteria of the OAPS and 650 did not (noncriteria OAPS). Data on antithrombotic-related complications were available in 1075 cases (65.15%). Overall, 53 (4.93%) women had bleeding complications, with 34 being considered minor (3.16%) and 19 major (1.76%). Neither obstetric complications nor laboratory categories were bleeding-related. Assisted vaginal delivery and caesarean section were related to local haemorrhage. Heparin doses and platelet count were not associated with major bleeding. CONCLUSIONS LDA and medium to high prophylactic LMWH during pregnancy in women with full-blown OAPS/noncriteria OAPS are safe. A slight increase in bleeding risk was noted in instrumental deliveries. No women who underwent spinal or epidural anaesthesia suffered bleeding complications. No haemorrhage was observed in cases where HCQ was added to standard therapy.

PROBLEM Antibody-mediated autoimmune diseases, such as autoimmune thyroid diseases (ATD), systemic lupus erythematosus (SLE), and antiphospholipid syndrome (APS), often are associated with recurrent fetal loss. One of the ATD is Hashimoto's thyroiditis which recently showed association with complications of pregnancy with increased levels of circulating autoantibodies reactive with epitopes on thyroid tissue such as thyroid peroxidase (anti-TPO). In retrospective study of sera analyses in patients with Hashimoto's thyroiditis, all patients had mainly elevated circulating anti-TPO autoantibodies. AIM We assessed the potential of human anti-TPO highly positive IgG, derived from patients with Hashimoto's thyroiditis sera associated with complications of pregnancy, to cause directly complications of pregnancy in murine model. METHOD OF STUDY Naive ICR female mice, infused intravenously with 100 μg of anti-TPO-positive IgG, showed increased fetal loss and embryo small for date (P

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated with pregnancy complications in patients with antiphospholipid syndrome (APS), but these results are not unanimously confirmed. To investigate if the detection of low C3/C4 could be considered a risk factor for adverse pregnancy outcomes (APO) in APS and aPL carriers’ pregnancies we performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p = 0.008). A subgroup analysis focusing on triple aPL-positive patients found that preconception low C3 and/or C4 levels were associated with an increased rate of pregnancy loss (p = 0.05). Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. This has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

To study disease activity during pregnancy and obstetric outcomes in patients with juvenile idiopathic arthritis (JIA) upon different subsets and with focus on medication use. Retrospective observational study of 22 pregnancies in 16 JIA patients (95.5% Caucasian) who were followed between 2010 and 2018. Disease activity, flares and medications were recorded before conception, during each trimester and postpartum period. Pregnancies occurred in 10 (45.5%) oligoarticular extended (OLA-E), 6 (27.3%) in polyarticular (PLA), 4 in (18.2%) systemic (SYS), 1 (4.5%) in oligoarticular persistent (OLA-P) and 1 (4.5%) in enthesitis-related arthritis (ERA) JIA patients. The median age at disease diagnosis and at conception was 5.5 and 28 years (respectively). The median disease duration was 20 years. Nineteen (95%) pregnancies started in a period of stable disease remission. Among the 22 pregnancies, 20 ended with a live birth (90.9%). No spontaneous miscarriages occurred; two voluntary interruption of pregnancy were performed. There were 7 flares in 6/20 pregnancies (35%) and 8 flares (8/22, 36.4%) occurred in postpartum period, all of them in OLA-E and PLA patients. Seven patients (35%) were taking biological disease-modifying anti-rheumatic drugs (bDMARDs) at conception, and 6 of them stopped this treatment at positive pregnancy test. Five patients resumed bDMARDs either during pregnancy (3 exposed during the third trimester) or puerperium due to a flare. Four preterm deliveries (20%) were recorded, all in patients who had a flare during pregnancy. The preconception counselling should include the evaluation of disease subset, as OLA-E and PLA may flare more than other subsets, especially if bDMARDs are discontinued at positive pregnancy test. Continuation of bDMARDs during pregnancy should be considered to minimize the risk of adverse pregnancy outcomes, particularly preterm delivery. Key Points • In our cohort, all the flares during pregnancy and 75% of postpartum flares were observed in patients who withdrew bDMARDs and cDMARDs at the beginning of pregnancy. • Flares were observed only in PLA and OLA-E patients. • Preterm delivery occurred in 20% of the pregnancies; all of these patients had a disease flare during pregnancy.

Background/Purpose To analyse complement variations during SLE pregnancies, considering pregnancies with Adverse Pregnancy Outcome (APO) and with flares. Methods Monocentric, retrospective study of 98 SLE patients with 134 pregnancies (including 3 twin pregnancies) prospectively followed by multidisciplinary team (1987–2015). Hypocomplementemia was defined according to the normality range calculated in healthy pregnancies by Reggia et al.1 Results APO occurred in 22 (16%) and flares in 11 (8%) pregnancies. The variation of mean C3 and C4 levels are shown in table 1. Notably, both in pregnancies with flares and with APO, there was no increase of C3 between the 2nd and the 3rd trimester and of C4 between the 1st and the 3rd trimester. In pregnancies with flares the mean levels of C3 and C4 were lower than in pregnancies without flares during the 2nd and the 3rd trimester; the mean levels of C4 were also lower in the flare group during pre-conceptional visit. In pregnancies with APO, the variation of C4 levels between the 2nd and the 3rd trimester was lower than in pregnancies without APO (-3.18 vs 0.27; p=0.01). The frequency of low C4 was higher in pregnancies with flare at pre-conceptional visit, 1st trimester and 3rd trimester (6/7 vs 25/103 p=0.002; 8/9 vs 56/106 p=0.04; 9/11 vs 33/96 p=0.003), as compared with pregnancies without flares. Conclusions In our cohort, low C4 at pre-conceptional visit seems to predict flares during pregnancies. Lower increase of C4 levels between the 2nd and the 3rd trimester could predict an APO. Reference Reggia R., Ziglioli T., Andreoli L., et al. Primary anti-phospholipid syndrome: any role for serum complement levels in predicting pregnancy complications?. Rheumatology 2012;51:2186–2190

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments.

BackgroundAntiphospholipid antibody syndrome (APS) is an autoimmune disease that affects women in childbearing age. In recent years, great improvements were achieved in the management of pregnancies in these women. Prematurity could be an issue in these pregnancies, mainly due to the direct pathogenic effect of antiphospholipid antibodies (aPL) on the placental surface. Maternal IgG aPL can cross the placenta and theoretically interact with the growing fetus; it could reach the fetal brain because of the incompleteness of the fetal blood-brain barrier: whether this can have an effect on brain development is still debated. Neonatal thrombosis episodes have been described in children positive for aPL, not always associated with maternal antibody positivity, suggesting the hypothesis of a possible aPL de novo synthesis in fetus and neonates.MethodsA keyword-based literature search was conducted. We also described a case of neonatal catastrophic antiphospholipid syndrome (CAPS).ResultsOffspring of patients with APS are generally healthy but the occurrence of neonatal thrombosis or minor neurological disorders were reported.ConclusionsThe limited number of the available data on this sensitive issue supports the need for further studies. Clinical follow-up of children of mothers with APS seems to be important to exclude, in the neonatal period, the occurrence of aPL associated pathological events such as thrombosis, and in the long-term, impairment in learning skills or behavioral problems.

Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on β2GPI domain (D) 1. Anti-β2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM). To this end, 135 women with persistently positive, medium/high titre anti-β2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash® β2GPI Domain 1 IgG and QUANTA Lite® β2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM.

Background Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta during pregnancy and theoretically reach the fetal brain. Some studies showed an increased number of learning disabilities in these children. Objectives To evaluate the long-term neurodevelopmental outcome of 40 children (median age 7.4 years) born to mothers with SLE and/or APS carrying positive IgG aPL during the third trimester of pregnancy. Methods Children were checked for neurological physical exam and intellectual/cognitive functioning by the Wechsler scale for corrected age. We submitted to the mothers the Child Behavior CheckList (CBCL) and a homemade set of questions created by pediatric neurologists. Results In all children neurological physical exam and intelligence levels were found to be normal. A cognitive impairment or a discrepant cognitive profile was found in 3 (7%) and 11 (28%) children, respectively. Learning disabilities were diagnosed in 3 children (19% of school-age children), all born to mothers with triple aPL positivity. A history of epilepsy was shown in four children (10%). Conclusions: Children born to women with SLE and/or APS may need a long-term follow-up focusing on milestones of neurodevelopment in order to detect and correct any alteration as early as possible.

Background:Patients with Spondyloarthritis (SpA) can experience flares during pregnancy and postpartum even though the available data are limited and not conclusive.Objectives:To assess disease activity and treatment modification during pregnancy and postpartum in patients with SpA and to identify risk factors for disease flare.Methods:Data on SpA pregnancies prospectively-followed in a pregnancy clinic from 2010 to 2019 were retrospectively analysed. Disease activity was assessed during each trimester and postpartum using ASDAS-CRP or DAS28-CRP. Flare was defined as an increase of disease activity leading to treatment modification (introduction or increase ≥5mg/day of prednisone, introduction of cDMARD or bDMARD)1.Results:Data on 50 pregnancies in 46 patients were collected (mean age at conception 33±4.7 years; median disease duration: 60 months (IQR 24-132); 33 psoriatic arthritis, 6 axialSpA, 2 reactive arthritis, 2 IBD-related SpA; 6 undifferentiated SpA, 1 juvenile idiopathic arthritis). Six pregnancies ended in miscarriage, so they weren’t considered for the analysis of flares during pregnancy (table 1). Fifteen out of 44 (34%) pregnancies had at least one flare during pregnancy (6, 7 and 4 during 1st, 2ndand 3rdtrimester respectively; 2 pregnancies had multiple flares). A higher rate of flare was observed in pregnancies of patients with axial involvement (p=0.01), on treatment with bDMARDs at preconceptional visit (p=0.03) and who stopped TNFi at positive pregnancy test (p=0.03). Peripheral involvement was associated with a lower rate of flares (p=0.02). Medications resumed during pregnancy were steroids (in 6 pregnancies), cDMARDs (2 sulfasalazine, 1 cyclosporine) and bDMARDs (4 certolizumab, 4 etanercept). During postpartum period flares were recorded in 46% of patients.Table 1.clinical features, medication and disease activity in pregnancies with flare vs without flareCLINICAL FEATURESFLARE (15)NO FLARE (29)pAxial involvement, n (%)11/15 (73)9/29 (31)0.01Peripheral arthritis, n (%)8/15 (53)26/29 (90)0.02Enthesitis, n (%)5/15 (33)14/29 (48)nsDactilitis, n (%)3/15 (20)8/29 (28)nsPsoriasis, n (%)6/15 (40)17/29 (59)nsIBD, n (%)2/15 (13)0nsUveitis, n(%)1/15 (7)3/29 (10)nsHLAB27 +7/11 (64)5/12 (42)nsMEDICATION HISTORYbDMARDs, n (%)11/15 (73)7/29 (24)0.003bDMARDs at preconception visit, n (%)8/15 (53)6/29 (21)0.04bDMARDs stopped at positive pregnancy test, n (%)7/15 (47)4/29 (14)0.03cDMARDs, n (%)12/15 (80)25/29 (86)nsDISEASE ACTIVITYACTIVE DISEASE* preconception visit, n(%)3/14 (21)4/23 (17)nsACTIVE DISEASE 1sttrimester, n(%)6/15 (40)1/29 (3)0.004ACTIVE DISEASE 2ndtrimester, n(%)8/15 (47)2/29 (7)0.001ACTIVE DISEASE 3rdtrimester, n(%)2/15 (13)1/29 (3)ns*DAS28-CRP>3.2 or ASDAS-CRP≥2.1Conclusion:In our cohort of prospectively-followed SpA pregnancies, 34% experienced a flare during pregnancy and 46% during postpartum. Flares occurred especially in those patients who discontinued TNFi early in pregnancy and with axial involvement. When resumed during pregnancy, TNFi was able to control the disease. At preconception counselling, the continuation of TNFi during pregnancy should be considered to ensure a better control of disease.References:[1]Fischer-Betz R et al.Arthritis Rheumatol. 2015; 67.Disclosure of Interests: :None declared

Background: During pregnancy, patients with rheumatoid arthritis (RA) can experience flares, which might influence pregnancy ouctomes. Objectives: To assess disease course during pregnancy and identify possible risk factors of disease flares in RA. Methods: Data on RA patients prospectively-followed in a pregnancy clinic were retrospectively analyzed before conception and during each trimester. Clinical characteristics, disease activity (DAS28-CRP3), medication use, and pregnancy outcomes were analyzed. Flare was defined by an increase of DAS28-CRP3 greater than 0.6. Results: Among 85 RA-pregnancies (mean age 34, SD 4,8; median disease duration 97 months, IQR 31-156) in 66 patients enrolled between 2010 and 2018, 8 pregnancies ended with early miscarriages, 1 with intrauterine fetal death and 2 were voluntary interrupted (1 for MTX exposure and 1 for encephalocele). The remaining seventy-four pregnancies in 62 patients were analyzed. Before conception, 52(71%) were in remission, 13(18%) in low disease activity and 8(11%) with moderate disease activity. Flares occurred in 29/74 (39%) patients during pregnancy (14/1° trimester,18 2° trimester,9 3° trimester). Flares occured more frequently in patients with a previous use of more than one conventional DMARDs (cDMARDs)(p 0,28) and a higher disease activity before conception (0,025) and in the 1°trimester (p 0,08). At conception, 30 (41%) patients were on biological DMARDs (bDMARDs) (16 ETA, 8 CTZ, 3 GOL, 2 ADA) and 16% with an active disease. 29 discontinued the treatment at positive pregnancy test and 8(27%) reintroduced bDMARDs because a flare during 1° (1 CTZ, 1 ETA), 2°(1 ADA, 2CTZ, 2 ETA) and 3° trimester (1 ETA) (Figure 1). 20/30(66%) experienced at least one flare during pregnancy.Forty-four (59%) patients were bDMARDs naive at conception (47% CCS, 41% HCQ, 16% SSZ, 2,3% MTX, 4,5% CyA), 6(7%) with an active disease. 16/44(36%) patients experienced at least one flare during pregnancy, 3 more than one flare (Figure 1). Seventeen live births were accompanied by complications (7 preterm deliveries, 2 very preterm deliveries, 6 premature rupture of membranes and 2 newborns small for gestational age). 60% of preterm births occurred in patients with a flare during pregnancy. Conclusion: In a cohort of prospectively-followed RA-pregnancies 39% of patients experienced at least one flare during pregnancy. A higher frequency was observed in patients on bDMARDs at conception after stopping the drug at positive pregnancy test. This suggests that patients with a more aggressive disease, as those on bDMARDs, require continuing treatment beyond conception. Counselling of patients on preconception treat-to-target management may help to achieve lower disease activity, especially in patients with a more severe disease (active disease or previous use of more than one cDMARDs). This may result in better pregnancy outcomes. Acknowledgement: None Disclosure of Interests: Maria Chiara Gerardi: None declared, Antia Garcia Fernandez: None declared, Laura Andreoli: None declared, Francesca Crisafulli: None declared, Matteo Filippini: None declared, Micaela Fredi: None declared, Roberto Gorla: None declared, Maria Grazia Lazzaroni: None declared, Cecilia Nalli: None declared, Marco Taglietti: None declared, Andrea Lojacono: None declared, Sonia Zatti: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis

Background Axial Spondiloarthrtis (AxSpA) can be active during pregnancy, especially in those patients who discontinued TNFi at the beginning of pregnancy. The severity of flare during pregnancy can influence the gestational outcome and the attitude of the physician towards treatment. Objectives To describe: 1)the disease course of AxSpA during pregnancies in patients who never used TNFi (bio-naive) and those who were TNFi users; 2)the severity of flares; 3)the impact of resuming TNFi in patients who experienced a flare during pregnancy (on both maternal disease control and gestational outcome). Methods Retrospective analysis of 18 prospectively-followed pregnancies from 2010 to 2018 in 15 patients with AxSpA. Two pregnancies ended in miscarriage, so they weren’t considered for the analysis of flares during pregnancy. Active disease was defined as ASDAS-CRP >2.1. Flare was defined as an increase of ASDAS-CRP greater than 0.6 with CRP elevation and one of the followings: introduction or increase above 5mg/day of prednisone, introduction of cDMARD or bDMARD. Results At preconception visit, 2 patients were on treatment only with steroids, 1 with sulfasalazine and steroids and 9 with bDMARDs (5 etanercept, 2 adalimumab, 2 golimumab; 2 with steroids). At conception, 3 patients presented active disease. TNFi was stopped at positive pregnancy test in 7 pregnancies; 1 patient continued TNFi over pregnancy. Twelve out of 16 (75%) patients had at least one disease flare (4, 10 and 3 during 1st, 2nd and 3rd trimester respectively). Among pregnancies with flare, medication resumed during pregnancy were steroids (7, 58%), cDMARDs (1 salazopyrine and 1 cyclosporine A, 17%) and bDMARDs (4 etanercept and 1 certolizumab, 42%). Six patients (38%) had a flare in postpartum period. Table 1 shows the comparison between pregnancies with and without flares during pregnancy. By comparing the pregnancies of patients with and without history of TNFi use (table 2), we have registered 8 flares (8/11, 73%) in the first group and 4 flare (4/5, 80%) in the second one. In the group of TNFi users, medications resumed during pregnancy were steroids in 5/11 (46%) and bDMARDs in 5/11 (46%), whereas in the group TNFi naive only in 1 pregnancy steroids was resumed and no bDMARDs were started. Mean ASDAS-CRP was higher in the group of TNF user. For what concerned gestational outcome, we did not observe any SGA, pre-eclampsia and eclampsia. Two pregnancies ended with miscarriage and 2 with preterm birth (at 36 and 34 gestational weeks). Two patients had PROM and 1 pPROM (this patient refused to resume TNFi during pregnancy and her flare was treated with medium doses of prednisone). Conclusion Three out of 4 AxSpA patients with severe disease phenotype and history of TNFi use prior to pregnancy experienced a disease flare after TNFi discontinuation at conception. Conversely, AxSpA patients with mild disease phenotype had a similar rate of flare during pregnancy but less severe and without the need for chronic treatment during pregnancy. When resumed during pregnancy TNFi was able to control disease activity and to favor a good gestational outcome. In preconception counselling the continuation of TNFi during pregnancy should be discussed with the patients. Disclosure of Interests Francesca Crisafulli: None declared, Laura Andreoli: None declared, Maria Chiara Gerardi: None declared, Antia Garcia Fernandez: None declared, Cecilia Nalli: None declared, Matteo Filippini: None declared, Roberto Gorla: None declared, Marco Taglietti: None declared, Micaela Fredi: None declared, Maria Grazia Lazzaroni: None declared, Andrea Lojacono: None declared, Sonia Zatti: None declared, Franco Franceschini: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis

Background: Data on the disease activity and pregnancy outcomes taking into account the different types of Juvenile idiopathic arthritis (JIA) patients are limited. Objectives: To analyze the course of disease during pregnancy and pregnancy outcomes in patients with JIA according to disease subtype, with focus on the medication use. Methods: A retrospective observational study was conducted on pregnant JIA patients followed in our pregnancy clinic between 2010 and 2018. Disease activity (DAS28-PCR3) was analyzed before conception, at each trimester and postpartum. Flare was defined as an increase in clinical activity leading to intensified therapy with at least one of: new prednisone, increase in dosage ≥5 mg/day, treatment with intraarticular glucocorticoids, (re-)treatment with DMARDS/TNFi. Pregnancy outcome were also recorded. Results: Sixteen patients and 22 pregnancies were included. Two pregnancies were voluntary interrupted (1 for Methotrexate exposure and 1 for fetal encephalocele). Table 1 summarizes disease features and pregnancy outcomes according to disease subsets. 10/22 (45,5%) were pregnancies observed in Oligoarticular Extended (OLA-E), 6 (27,3%) Polyarticular (PLA), 4 (18,2%) Systemic (SYS), 1 (4,5%) Oligoarticular (OLA) and 1 (4,5%) Enthesitis related Arthritis (ERA) JIA patients. At conception 19(95%) pregnancies were on remission, 1(5%) OLA-E patient in low disease activity. Among the 20 pregnancies ended with a live birth, 1 OLA, 4 SYS and 1 ERA patients mantained sustained remission, without cDMARDs or bDMARDs, throughout pregnancy. There were 7 flares in 6 (31,8%) pregnancies, 5 (71,4%) of them among PLA patients and 2 (28,6%) among OLA-E patients. No extrarticular flare was recorded. There was no flare among SYS, OLA and ERA patients. One pregnancy in a patient with PLA JIA (4,5%) was characterized by more that one flare, but none had more than two flares. Most of flares (2/29% 1^trimester, 4/57% 2^trimester, 1/14% 3^trimester) occurred during 2^trimester. Eigth flares occurred in postpartum, also in 2 pregnancies after voluntary pregnancy interruption. Regarding treatment at conception; 8 (40%) pregnancies were on bDMARDs, treatment was stopped at positive pregnancy test in 6 pregnancies, 2 (33,3%) required restart of treatment due to a flare in 1^Trimester (1 CTZ) and 3^Trimester (1 ETA), and 3 flared in puerperium with restart of bDMARDs. Two (25%) pregnancies continued bDMARDs at positive pregnancy test throughout the pregnancy to prevent a flare, that had been already experienced in previous pregnancies (not followed in our centre). Regarding pregnancy complications and outcomes, no cases of Preeclampsia, eclampsia, small for gestational age babies, intrauterine death, were observed. One pregnancy was complicated with pre-term premature rupture of membranes at 35 gestational week, in a patient not taking prednisone. There were 5 (25%) pre-term deliveries. Conclusion: Nearly one third of pregnant patients with JIA had a disease flare during pregnancy. Flares were observed only in 2 disease subsets (PLA; OLA-E) and associated with discontinuation of bDMARDs at positive pregnancy index. The preconception counseling of patients with JIA should include the disease subset in the risk stratification and consequently the continuation of bDMARDs during pregnancy. Maternal disease control is necessary to minimize the risk of adverse pregnancy outcomes (especially pre-term birth). Disclosure of Interests: Antia Garcia Fernandez: None declared, Laura Andreoli: None declared, Maria Chiara Gerardi: None declared, Francesca Crisafulli: None declared, Cecilia Nalli: None declared, Matteo Filippini: None declared, Roberto Gorla: None declared, Marco Taglietti: None declared, Micaela Fredi: None declared, Maria Grazia Lazzaroni: None declared, Andrea Lojacono: None declared, Sonia Zatti: None declared, Franco Franceschini: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis

Background: T-cells play a role in pathogenesis of rheumatoid arthritis (RA) and in its cardiovascular (CV) comorbidities [1]. CD3+CD31+CXCR4+T-cells may be involved in damaged endothelium repair [2]. The percentage of these cells in the peripheral blood was reported to be lower in RA than in healthy controls, as an effect of disease activity rather than of traditional CV risk factors [3]. Abatacept (ABA), a T-cell co-stimulation blocker, is approved for the treatment of RA. In addition to its effect on disease activity, it may have a CV protective action [4]. Objectives: To evaluate CD3+CD31+CXCR4+T-cells in a cohort of RA patients in correlation with disease activity, CV parameters, and the potential effect of ABA therapy. Methods: Thirty-one RA patients (median[10th-90thpercentile] age=60[40-70] years, baseline C-reactive protein (CRP)-DAS28=4[3-5.4], body mass index (BMI)=21[17.3-28.6] kg/m2, rheumatoid factor (RF) positive:55%, anti-citrullinated peptide autoantibodies (ACPA) positive:77%) were enrolled. Thirteen patients were evaluated before and after 6 months of ABA therapy. Among them, in 5 patients without known CV risk factors (history of arterial hypertension, diabetes, hypercholesterolemia, previous CV events and smoking), a morphological evaluation of retinal arterioles was performed by adaptive optics, a validated technique quantifying microvascular damage [5]. The response to treatment was evaluated with the EULAR response criteria. Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry. Results: At baseline, no correlation was found between relative CD3+CD31+CXCR4+T-cell number and age, BMI, CRP DAS28, RF and ACPA titer. However, a negative correlation was observed with retinal wall thickness (Figure1). After ABA therapy (n=13), no significant differences were found between good-moderate responders (n=10) and non-responders (n=3), but the two groups seemed to show an opposite trend (T0 vs T6; from 23.8[4-45.4] to 11.9[5-38.7] and from 20.4[15.4-32.3] to 27.4[17.8-41]% of CD3+ cells, respectively). All 5 patients without known CV risk, evaluated also with adaptive optics, had a good EULAR response. A trend for reduction of CD3+CD31+CXCR4+T-cells after ABA therapy was also observed (19[7.9-45.6] vs 12.4[4.6-26.1]% of CD3+), as well as of the retinal wall thickness (14.4[12.9-16.2] vs 14.2[11.7-14.9] μm). A significant reduction of retinal wall cross-sectional area was observed (5123.3[4027.8-6145.5] vs 4852.3[3554.9-5788.2] μm2;p=0.04). Conclusion: In a subgroup of patients without known CV risk factors, CD3+CD31+CXCR4+T-cell number was inversely related to the possible presence of subclinical CV involvement, as evaluated by retinal microvascular damage. This improved after ABA therapy. These findings may suggest a possible value of CD3+CD31+CXCR4+T-cell number in the evaluation of microvascular damage, and a possible beneficial effect of ABA on the microcirculation in RA patients. Reference [1] Dessein PH, J Rheumatol2005. [2] Hur J, Circulation 2007. [3] Rodriguez Carrio J, ARD 2015. [4] Kallikourdis M, Nat Commun 2017. [5] De Ciuceis, J Hypertens2018. Acknowledgement: Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct. Disclosure of Interests: Silvia Piantoni: None declared, Francesca Regola: None declared, Stefano Caletti: None declared, Rajesh Kumar: None declared, Cecilia Nalli: None declared, Chiara Bazzani: None declared, Claudia Rossini: None declared, Carolina De Ciuceis: None declared, Damiano Rizzoni: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis, Paolo Airo: None declared

Background Treatment with tumor necrosis factors inhibitors (TNFi) during pregnancy may be required in order to control maternal disease which itself can be a threat for maternal-fetal well-being and pregnancy outcome. Information about the follow-up of in utero exposed offspring is limited Objectives The aim of this study was to compare the health and developmental conditions of children born to mothers with chronic arthritis who were exposed in utero to TNFi with those of unexposed children born to patients with the same age at conception and disease. Methods An ad-hoc created questionnaire was used to collect data on birth and growth parameters, breastfeeding, weaning, developmental milestones, vaccinations and illnesses. Results 122 live births in 97 women with chronic arthritis (65 RA and 32 SpA) were observed: 59 pregnancies were exposed to TNFi at the time of conception and 63 pregnancies were TNFi-naive. In 57/59 (97%) pregnancies, TNFi was discontinued at positive pregnancy index. In 2/59 (3%) pregnancies TNFi was mantained throughout pregnancy due to active disease at conception. TNFi was restarted in 16/57 pregnancies (28%) (10 ETA, 5 CTZ, 1 ADA) during the 2nd-3rd trimester due to moderate-severe flare (median exposure 22 weeks; discontinuation of TNFi between 32-39 gestational weeks). In second group, TNFi (1 ETA, 1 CTZ) was introduced in 2/63 (3%) pregnancies during the 2nd trimester due to a severe flare. 16 in 16/63 (25%) pregnancies were managed with an increase of prednisone (max 10mg/day). To investigate the long-term follow-up of children exposed in utero to TNFi, 61 children exposed to TNFi at conception or during 2nd-3rd trimester (median age 29 months) and 61 unexposed children (median age 49 months) were compared. No significant differences in growth parameters and developmental milestones were observed. No excess nor particular pattern of congenital defects/malformations were observed. In both groups, vaccinations were performed according to the national schedule (no live vaccines in the first year of life) without relevant complications (Figure 1). Conclusion TNFi may be required in patients that experienced flare during pregnancy and they are effective in controlling maternal disease and ensures a good pregnancy outcome without complications for the health and growth of exposed children. Acknowledgement None Disclosure of Interests Maria Chiara Gerardi: None declared, Laura Andreoli: None declared, Chiara Bazzani: None declared, Matteo Filippini: None declared, Micaela Fredi: None declared, Roberto Gorla: None declared, Maria Grazia Lazzaroni: None declared, Cecilia Nalli: None declared, Marco Taglietti: None declared, Andrea Lojacono: None declared, Sonia Zatti: None declared, Mario Motta: None declared, Angela Tincani Consultant for: UCB, Pfizer, Abbvie, BMS, Sanofi, Roche, GSK, AlphaSigma, Lillly, Jannsen, Cellgene, Novartis

Pregnancy in autoimmune diseases remains an argument of debate. In last years great improvements were done and with the correct medical support women with disease such as Systemic Lupus Erythematosus or Antiphospholipid Syndrome can afford a pregnancy and have healthy babies. The starting point is a good counselling. Women should be informed about risks that can occur taking some medications while pregnant and, on the other hand, that there are medications that can be safety assumed during pregnancy. Furthermore, there are known maternal risks factor such as the presence of antiphospholipid antibodies or anti-Ro/SSA antibodies that must be carefully manage by both rheumatologists and obstetrics. In addition, also disease activity during pregnancy can represent an issue. For all these reason, a multidisciplinary approach is mandatory in order to give our patients an optimal medical support, before, during and after pregnancy.

Infertility consists by definition in" failure to achieve a clinical pregnancy after 12 months or more of regular unprotected intercourse" while the term subfertility means a delay to achieve pregnancy. Several factors can contribute to infertility or subfertility in patients with systemic autoimmune diseases. The association of systemic autoimmune conditions with endometriosis, celiac disease and thyroid autoimmunity that are well known causes of infertility and/or subfertility need to be taken in consideration when difficulties in the onset of pregnancy is reported. The majority of the used antirheumatic drugs do not interfere with fertility. However, the use of cyclophosphamide, limited to severe disease, can provoke premature ovarian failure; to preserve fertility a preventive treatment is available. Nonsteroidal anti-inflammatory drugs can cause temporary infertility and corticosteroids are associated to a prolonged time to pregnancy in some rheumatic diseases. Data on the association of antiphospholipid antibodies (aPL) with infertility are still debated but in general an increased rate of aPL is described patients undergoing medically assisted reproductive techniques. In systemic lupus erythematosus aPL and other autoantibodies (i.e. anti-oocytes) can contribute to the infertility of some patients. Subfertility, rather than infertility, is observed in patients with rheumatoid arthritis; the particular physical conditions of these women can also account for this. Physicians should not forget the patients' age, that is mandatory in order to preserve their chance to have children.

Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.

Background The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. Objective To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β2-glycoprotein-I antibody (aβ2GPI) ELISA testing results. Methods Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. Results 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ2GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ2GPI). Conclusions The results of inclusion for aCL and aβ2GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ2GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS.

Background:T-cells play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and in its cardiovascular (CV) comorbidities, acting at microvascular level [1]. Since small artery remodeling is the earliest form of target organ damage in hypertension, the evaluation of microvascular alterations might provide clinically useful information. The evaluation of retinal arterioles is a non-invasive technique to identify a precocious microvascular damage, which is related to an increase of the wall-to-lumen ratio (WLR) [2]. CD3+CD31+CXCR4+ T-cells may be involved in damaged endothelium repair and are increased in patients with morphological microvascular alterations [3]. In addition to its effect on disease activity, abatacept (ABA), a co-stimulator blocker which is approved for the treatment of RA, may have specific CV protective action, modulating the numbers of certain subtypes of lymphocytes [4].Objectives:To non-invasively investigate morphological characteristics of retinal arterioles and to evaluate CD3+CD31+CXCR4+T-cells in a cohort of RA patients treated with ABA.Methods:Eleven RA patients [median (25th-75thpercentile) age=58 (50-65) years, baseline C-reactive protein (CRP)-DAS28=4.4 (3.8-4.6), body mass index (BMI)=23.4 (21.6-25.6) kg/m2, rheumatoid factor (RF) positive:45%, anti-citrullinated peptide autoantibodies (ACPA) positive:73%] without known CV risk factors (arterial hypertension, diabetes, hypercholesterolemia, previous CV events, smoking) were evaluated by adaptive optics, a validated technique quantifying microvascular damage [5], before and every 6 months of therapy with ABA (T0, T6 and T12). Phenotypic analysis of peripheral blood T lymphocytes was made by flow-cytometry in 5 patients of the cohort at T0 and T6.Results:A progressive significant reduction of the WLR of retinal arterioles was observed [T0=0.28 (0.25-0.30), T6=0.27 (0.24-0.31), T12=0.23 (0.23-0.26); p T0 vs T6=0.4; p T6 vs T12=0.01; p T0 vs T12=0.01] (Figure 1), without significant variations in the other parameters [internal diameter: T0=94.4 (84.1-104.0), T6=94.8 (84.6-107.7), T12=99.2 (89.1-109.1) µm; external diameter: T0=125.8 (111.1-131.0), T6=122.4 (109.1-134.5), T12=125.6 (113.9-134.4) µm; wall thickness: T0=13.2 (12.2-14.4), T6=13.4 (11.7-14.4), T12=12.5 (11.6-13.0) µm; wall cross-sectional area: T0=4581.0 (3788.7-5263.7), T6=4563.3 (3788.5-5295.2), T12=4099.7 (3899.0-5145.7) µm2)]. In 5 patients evaluated also for T-cell immunophenotyping a negative correlation was observed between CD3+CD31+CXCR4+ T-cell number and the retinal wall thickness at baseline (R=0.871;p=0.05). After ABA therapy a trend for reduction of CD3+CD31+CXCR4+T-cells [19.0 (13.8-38.3) vs 12.4 (5.2-18.0) % of CD3+], was observed as well as of significant reduction of retinal wall cross-sectional area [5123.3 (4385.0-5470.3) vs 4852.3 (4118.3-5228.0) µm2;p=0.04].Conclusion:In a cohort of RA patients without known CV risk factors, a reduction in retinal microvascular alterations arterioles was demonstrated after treatment for 12 months with ABA. CD3+CD31+CXCR4+T-cell number was inversely related to the possible presence of subclinical CV involvement. These results may suggest the possibility of microvascular abnormalities regression induced by the immune system modulation.References:[1]Dessein PH, J Rheumatol 2005.[2]Rizzoni D, Am J Hypertens. 2018.[3]Hur J, Circulation 2007.[4]Kallikourdis M, Nat Commun 2017.[5]De Ciuceis C, J Hypertens 2018.Acknowledgements:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduct.Figure 1.Disclosure of Interests:None declared

Background:Belimumab (BEL) is a monoclonal antibody approved for SLE treatment but few data are available about its use before or during pregnancy.Objectives:Our study aims to describe pregnancies in SLE patients who have discontinued BEL before conception, at positive pregnancy test or during pregnancy.Methods:Data from prospectively-followed pregnancies (2014-2020) in SLE patients treated with BEL in 3 Italian centers where retrospectively collected, focusing on maternal disease activity, obstetric and neonatal outcome. Continuous data are expressed as median [min-max].Results:Thirteen SLE pregnancies were analyzed (median age at conception 32 [24-41] years; 77% spontaneous, 69% primigravidae). All patients had positive ANA and anti-dsDNA antibodies; 4 had anti-Ro antibodies (31%); 4 had anti-phospholipid antibodies (aPL; 1 single, 2 double and 1 triple positivity). Seven patients (54%) had a history of lupus nephritis (LN); 2 patients (15%) had a concomitant diagnosis of antiphospholipid syndrome (1 thrombotic-APS and 1 thrombotic+obstetric-APS).Ten (77%) pregnancies were planned and the use of BEL with regard to pregnancy was agreed with the patient during preconception counseling. At preconception visit, 8 patients were in remission while 5 had active disease (median SLEDAI 3 [0-8]).BEL (11 intravenous, 2 subcutaneous) was stopped in 2 cases before conception, in 7 at positive pregnancy test and in 4 during pregnancy (2 at 11th week, 1 at 22nd, 1 at 24th); median duration of treatment at discontinuation was 29 [4-68] months. Other treatments during pregnancy were: oral prednisone in 12 cases (92%); intravenous methylprednisolone in 1 (8%); hydroxychloroquine in 10 (77%); chloroquine in 1 (8%); azathioprine in 5 (39%); calcineurin inhibitors in 5 (39%); low-dose acetylsalicylic acid in 10 (77%); low molecular weight heparin in 9 (69%).Three flares occurred during the 3rd trimester in patients who stopped BEL at positive pregnancy test.Live-births occurred in 92% of the pregnancies. A patient with thrombotic+obstetric-APS and LN, underwent assisted reproductive technology (embryo donation) and developed eclampsia (25thweek), an urgent cesarean section was performed and the newborn died after 3 days. One pre-eclampsia occurred in a patient with history of LN, double aPL positivity and active disease. One miscarriage at 11th week occurred; no early miscarriages (th week) were recorded. Pregnancy complications and outcomes are reported in Table 1.Table 1.Pregnancy complications and outcomes according to the timing of discontinuation of BEL.BEL STOPPED PRECONCEPTIONALLY(2)BEL STOPPED AT POS PREGNANCY TEST(7)BEL STOPPED DURING PREGNANCY(4)Pre-eclampsia0/20/71/4 (25%)Eclampsia0/20/71/4* (25%)Gestational Diabetes0/21/7 (14%)0/4IUGR0/21/7 (14%)1/4* (25%)pPROM/PROM0/20/71/4 (25%)Live birth1/2 (50%)7/7 (100%)4/4 (100%)Severe pre-term birth(≤ 34thweek)0/20/71/4* (25%)Late pre-term birth(35th- 37thweek)0/23/7 (43%)0/4Small for Gestational age neonate0/24/7 (54%)1/4 (25%)Late miscarriage (>10thweek)1/2 (50%)0/70/4Perinatal death0/20/71/4* (25%)IUGR: IntraUterine Growth Restriction; PROM: Premature Rupture of Membrane; pPROM: pretermPROM; *in the same patient (history of thrombotic and obstetric-APS and lupus nephritis) who underwent Assisted Reproductive Technologies (embryo donation).No malformations were recorded. Two newborns were transferred to the Intensive Care Unit (1 for milk protein intolerance and 1 for desaturation).Eight newborns received vaccinations according to national schedule (missing data for 3). Five newborns were breastfed, 1 received formula milk and 5 mixed-feeding. BEL was resumed in 7/13 patients after pregnancy (in 4 cases for flare), after a median period of 5 [4-22] months.Conclusion:While more data are needed, this small series suggests that BEL might be a therapeutic option for SLE patients during pregnancy planning, similarly to other biological drugs used in chronic forms of arthritis.Disclosure of Interests:None declared

Background:In SLE pregnancies adverse pregnancy outcomes (APO) are more frequent than in general obstetric population (GOP). In clinical practice, low C3 and C4 levels are associated with active disease and, during pregnancy, complement activation products are shown to be associated with APO.Objectives:To analyse complement variations during SLE pregnancies, focusing on disease flares and APO.Methods:Data on SLE pregnancies prospectively-followed by multidisciplinary team in 2 Italian Centers from 1987 to 2018 were retrospectively analysed. C3 and C4 normal levels were calculated in general obstetric population (GOP) as previously described1, and related to maternal and fetal outcome. Non categorical variables were compared using Mann-Whitney test or Wilcoxon test when appropriate.Results:Two hundred forty-six pregnancies in 172 SLE patients were analysed (mean age at conception 31.3 ±4.9 years; mean disease duration 8.3 ±7.1). Anti-Ro antibodies were positive in 64 patients (37%) and anti-phospholipid antibodies (aPL) were positive in 84 (48%), with single positivity in 54%, double in 24% and triple in 21%; 9 patients (5%) had also a diagnosis of obstetric-antiphospholipid syndrome (APS) and 8 (4%) had thrombotic-APS. Seventy-one patients (41%) had history of Lupus Nephritis.Thirty-five flares were recorded in 30 pregnancies (12%). APO occurred in 47 pregnancies (19%) and were: 27 fetal loss (20 early miscarriage th week and 7 intrauterine fetal death), 11 severe preterm birth (th week) and 15 hypertensive disorder (11 pre-eclampsia and 5 pre-eclampsia+HELLP syndrome).In GOP, C3 progressively increased throughout pregnancy and C4 increase from the 1st trimester to the 2nd trimester, as well as in SLE pregnancies without flares and without APO, from preconception (Fig 1). In the other SLE groups, C3 and C4 showed a different trend: in pregnancies with flares, they did not increase from preconception to the 1st trimester; in fetal losses and severe pre-term births, they remained stable throughout pregnancy; in hypertensive disorders they increased only between preconception and the 1st trimester.C3 and C4 levels were higher in GOP than in all SLE pregnancies groups (including those without flares and without APO) in each trimester. SLE pregnancies without flares showed higher C3 and C4 levels than pregnancies with flares, at preconception and in each trimester. SLE pregnancies without APO had higher C3 and C4 levels than pregnancies with fetal death at 2nd trimester, higher C3 levels than severe pre-term births in each trimester and higher C4 at 3rd trimester (Fig.1).At preconception, pregnancies with flares showed a higher frequency of low C3 and of low C4 than in pregnancies without flares (76% vs 42%, p=0.01; 76% vs 26%, pst: 82% vs 48%, p=0.003; 2nd: 82% vs 64%, p=0.01; 3rd: 64% vs 30%, p=0.002). At multivariate analysis, low C4 at preconception was associated with flare (OR [95% CI]: 10.34 [2.52-42.39]; p=0.001).Figure 1.Variations of C3 and C4 median levels (mg/dL) throughout pregnancy in GOP1 and in SLE pregnancies without and with flare (a) and without and with APO (b).* p ^as compared with SLE groups: pConclusion:In SLE pregnancies, monitoring of C3 and C4 is important: its failure to increase can be useful to recognize potential risk situations which deserve particular monitoring.References:[1]Reggia R. et al. Rheumatology 2012;51:2186-2190.Disclosure of Interests:None declared

Background:In rheumatic diseases, specifically in chronic inflammatory arthritis (IA), there are no data about the effectiveness of LDA in preventing pregnancy complications.Objectives:To assess the potential benefit of LDA administration during pregnancy to prevent adverse pregnancy outcomes (APO) in IA.To compare pregnancy outcomes in IA pregnancies treated during pregnancy with LDA with those untreated.Methods:Italian P-RHEUM.it register is designed as a nationwide, web-based longitudinal observational cohort study collecting data on pregnancies in inflammatory rheumatic diseases. At baseline, socio-demographic parameters, obstetric history, comorbidities and clinical/laboratoristic characteristics are registered. During pregnancy, the course of maternal disease, medications, development of fetus and complications are collected for each trimester.Results:From May 2018 to May 2020, 349 patients were enrolled. Forty-five patients with IA had completed their pregnancy with known outcome (20 Rheumatoid Arthritis, 10 Psoriatic Arthritis, 6 Ankylosing spondylitis, 5 Juvenile Idiopathic Arthritis, 4 Undifferentiated Arthritis): 13 (28.89%) treated with LDA during pregnancy and 32 (71.11%) without LDA prophylaxis. LDA was used with a higher frequency in women with previous APO, anti-phospholipid positivity and on biological DMARDs even if it’s not statistically significant (Table 1). All the LDA-treated women had a live-birth rate of 100%, whereas among women not treated with LDA the live birth rate was of 84.4% with 27 live-birth pregnancies, 3 early miscarriages, 1 fetal loss and 1 stillbirth observed. There were no significant differences between the LDA and the not LDA groups regarding pregnancy/peripartum obstetric complications (p=0.14), although less adverse pregnancy/peripartum outcomes were registered in LDA patients’ group (Table 1).Conclusion:The preliminary data of this prospective cohort study show that LDA improve pregnancy outcome in IA even if women treated with LDA had more risk factors for APO. The extension of this cohort will allow us to further investigate these important results.References:[1]Roberge S, et al. AmJObstetGynecol.2017;216:110-120.e6.[2]Andreoli L et al. Annals of the Rheumatic Diseases 2017;76: 476–85.[3]Sammaritano L et al. Arthritis & Rheumatology 2020; 72: 529–56.Table 1.Comparison between inflammatory arthritis pregnancies treated with low-dose aspirin and those untreated.LDA (n 19)Not LDA (n 39)pMaternal age at conception, median (IQR)33 (30.5 - 36.5)33 (28.2 - 35)BMI, median (IQR)25.4 (22.9 - 28.5)22.5 (20.4 - 24.5)Smoking, n (%)3 (15.8%)4/36 (11.1%)0.68Previous APO, n (%)7/11 (63.7%)7/13 (56.1%)0.34aPL+, n (%)3 (15.8%)1/36 (2.8%)0.1CRP+, n (%)5/15 (33.3%)11/27 (40.7%)0.75GC at baseline, n (%)9 (47.4%)15/34 (44.1%)0.82cDMARDs at baseline, n (%)1 (5.3%)3/34 (8.8%)1bDMARDs at baseline, n (%)6 (31.6%)11 (28.2%)0.79Live-birth pregnancy, n (%)18 (94.7%)32 (82.1%)0.25Pregnancy loss, n (%)1 (5.3%)7 (17,9%)0.25Hypertensive disorders, n (%)2/18 (11.1%)6/38 (15,8%)1HELLP syndrome, n (%)0 (0%)0 (0%)1PROM, n (%)0 (0%)3/38 (7.9%)0.54Preterm delivery, 34-37 GW, n (%)2 (10.5%)2 (5.2%)0.59Preterm delivery, 1 (5.3%)1 (2.6%)1IUGR, n (%)0 (0%)3 (7.8%)0.54SGA, n (%)0 (0%)0 (0%)1Pregnancy/Peripartum complications, n (%)3 (15.8%)11 (28.9%)0.35Legend: aPL, Antiphospholipid syndrome; bDMARDs, biological disease-modifying antirheumatic drugs; BMI, Body mass index; cDMARDs, Conventional disease-modifying antirheumatic drugs; CRP, C-reactive protein; GC, Glucocorticoids; GW, gestational week; HELLP, haemolysis, elevated liver enzymes, and low platelets; Hypertensive disorder defined as gestational hypertension, preeclampsia and eclampsia; IQR, Interquartile range; IUGR, intrauterine growth restriction; LDA, Low-dose Aspirin; Pregnancy loss defined as early fetal-loss, miscarriage and still-birth; PROM, Premature rupture of membranes; SGA, Small for gestational age.Acknowledgements:I would like to acknowledge the Epidemiology Unit of the Italian Society for Rheumatology and the Investigators of the Italian Registry.Disclosure of Interests:None declared

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

Background:The World Health Organization recommends that infants should be exclusively breastfed until the age of 6 months. The aim of this study was to assess the ratio of breastfeeding patients with Rheumatic Diseases (RD) and to identify possible causes of its discontinuation.Objectives:The aim of this study was to assess the ratio of breastfeeding patients with Rheumatic Diseases (RD) and to identify possible causes of its discontinuation.Methods:This study was embedded in the P-RHEUM.it register, as a nationwide prospective cohort study collecting data of pregnancies in inflammatory RD. Pregnancies, enrolled until the 20th week of pregnancy, are followed from pregnancy until 6 months postpartum. At baseline, sociodemographic parameters, obstetric history, comorbidities are reported. During pregnancy, the course of maternal disease, development of foetus and complications are reported. After delivery, the pregnancy outcome, data on lactation and child development are collected.Results:From May 2018 to May 2020 data of 349 patients were available. Data on lactation were available in 44 pregnancies. Two months after delivery 37 were continuing breastfeeding (n=26) or mixed feeding (n=11), while 7 were using formula feeding. Among patients using formula feeding 2 had a diagnosis of rheumatoid arthritis (RA), 1 of juvenile idiopathic arthritis, 1 of undifferentiated arthritis (UA), 1 of anti-phospholipid syndrome (APS), 1 of vasculitis and 1 of systemic lupus erythematosus. The reasons of formula feeding were the following: 2 for agalactia, 2 for personal preferences, 3 for drug-related concerns (1 for physician’s decision in a patient with APS; 2 for maternal concerns about drugs in patients with RA and UA treated respectively with Adalimumab and Tocilizumab). At 6 months 30 continued breastfeeding (n=23) or mixed feeding (n=7) and 14 formula feeding. The reasons of formula feeding were available in 9 patients: 3 for agalactia, 2 for personal preferences, 2 for physician’s decision in a patient with APS and in a patient positive for anti-phospholipid antibodies; 2 for maternal concerns about drugs.Conclusion:Preliminary data of this prospective study demonstrate a high percentage of breastfeeding/mixed feeding after delivery and after 6 months among women with RD. Drug related concerns are the main reason of discontinuation of breastfeeding, although medication results compatible with lactation. Using our results, strategies supporting patients with RD whishing to breastfeed may be developed.References:[1]Carina Gotestam Sporken et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 2016.[2]Sammaritano et al. 2020 American College of Rheumatology Guideline for the management of reproductive health in rheumatic and muscoloskeletal diseases, Arthritis Rheumatol. 2020.Acknowledgements:Authors would like to thank SIR study center and all patients who accepted to partecipate to our studyDisclosure of Interests:None declared

Background:SLE pregnancies have an increased risk of Adverse Pregnancy Outcomes (APO). In clinical practice, low C3 and C4 levels are associated with active disease and, during pregnancy, complement activation products are shown to be associated with APO.Objectives:To analyse potential association between C3 and C4 variations and disease flares and APO during SLE pregnancies.Methods:Demographic, clinical and laboratory data on SLE pregnancies prospectively-followed by a multidisciplinary team in a pregnancy clinic from 1987 to 2015 were retrospectively analysed at preconception and at each trimester. Hypocomplementemia was defined according to the normality range calculated in healthy pregnancies by Reggia et al1. APO were defined as: early miscarriage (thweek), intrauterine fetal death (>10thweek), perinatal death (thday of life), pre-eclampsia (PE), severe preterm birth (thweek).Results:134 pregnancies in 98 SLE patients were analysed. APO occurred in 22 (16%) pregnancies: 9 early miscarriages, 4 intrauterine fetal deaths, 3 severe preterm births, 6 PE (hesitated in 1 intrauterine fetal death, 1 perinatal death; 2 preterm birth between 34thand 37thweeks and 2 term births). 13 flares (2 renal, 4 articular, 6 cutaneous and 1 neurological) were recorded in 11 (8%) pregnancies.The mean C3 and C4 levels at each trimester are shown in table 1.Table 1.C3 and C4 mean levels (mg/dL) at pre-conceptional visit (T0), 1sttrimester (T1), 2ndtrimester (T2) and 3rdtrimester (T3).C3 T0C3 T1C3 T2C3 T3p T0-T1p T1-T2p T2-T3Pregnancies with flares73.282.283.897.50.040.020.06Pregnancies without flares85.391.8104.4114.7Pregnancies with APO*84.791.598.5106.30.030.030.89Pregnancies without APO*84.590.9102.8112.8C4 T0C4 T1C4 T2C4 T3p T0-T1p T1-T2p T2-T3Pregnancies with flares8.611.810.911.40.010.430.27Pregnancies without flares13.214.716.316.60.98Pregnancies with APO**13.116.115.914.70.010.30.13Pregnancies without APO**12.914.215.816.10.42Comparison of C3 and C4 mean levels between pregnancies with APO vs without APO:* T0, T1, T2, T3: ns; ** T0, T1, T2, T3: nsBoth in pregnancies with flares and with APO, there was no increase of C3 between the 2ndand the 3rdtrimester and of C4 between the 1stand the 2ndtrimester.At preconception, mean levels of C4 were lower in pregnancies with flares compared to those without flares (images 1 and 2); during the 2ndand the 3rdtrimesters the mean levels of both C3 and C4 were lower in pregnancies with flares.In pregnancies with APO, the variation of C4 levels between the 2ndand the 3rdtrimester was lower than in pregnancies without APO (-3.18 vs 0.27; p=0.01).A higher frequency of low C4 was observed at pre-conceptional visit, 1sttrimester and 3rdtrimester (6/7 vs 25/103 p=0.002; 8/9vs56/106 p=0.04; 9/11 vs 33/96 p=0.003) in pregnancies with flare as compared with pregnancies without flares.Figure 1.Image 1: comparison of C3 mean levels between pregnancies with faresvswithout flaresFigure 2.Image 2: comparison of C4 mean levels between pregnancies with faresvswithout flaresConclusion:In our cohort of prospectively-followed SLE pregnancies, low C4 levels at preconception seems to predict flares during pregnancy. Low increase of C4 levels between the 2ndand the 3rdtrimester could predict an APO.References:[1]Reggia R. et al. Rheumatology 2012;51:2186-90Disclosure of Interests:None declared

Background:Soluble intercellular adhesion molecule 1 (ICAM1) and C-X-C motif chemokine 13 (CXCL13) were described as differentially associated with two major subtypes of synovitis in rheumatoid arthritis (RA). Raised serum levels of ICAM1 (which is upregulated in synovial fibroblasts in response to TNFα), and of CXCL13 (which is expressed by synovial follicular dendritic cells and activated mature antigen-experienced T-helper cells), are associated with a myeloid or lymphoid synovial phenotype, respectively (1). It has been suggested that a preferential clinical response to anti-TNFα, as compared to anti-IL-6R monotherapy, can be predicted by measuring these two biomarkers (2). No information is available on the possible utility of these biomarkers in RA patients treated with abatacept (ABA), a T-cell co-stimulation blocker.Objectives:To analyze the effect of ABA on ICAM1 and CXCL13 serum levels in RA and to verify whether they predict the response to the drug.Methods:63 RA patients [F/M=51/12; median (10th-90thpercentile) age=60 (41-72) years; CRP-DAS28=4.6 (3.3-5.8); ACPA positive: 86%], before and after 6 months of treatment with ABA + methotrexate and 22 sex and age-matched healthy controls (HC) were evaluated. Serum ICAM1 and CXCL13 levels were dosed by commercial ELISA (Life Technologies and R&D). Response to treatment was defined with the EULAR criteria.Results:CXCL13 serum levels were higher in RA at baseline than in HC [136 (42-325) vs 32 (19-57) pg/ml, pConclusion:Our results confirmed that CXCL13 serum levels are directly correlated with disease activity and demonstrated that ABA therapy induces their reduction. These findings suggest that the co-stimulation blockade at central level and/or in the synovium lead to a reduced production of CXCL13. We could not demonstrate that CXCL13 levels predict the clinical response to ABA in this cohort of patients.References:[1]Rosengren S, Rheumatology 2011;2.Dennis G, Arthritis Res Ther 2014Acknowledgments:Bristol-Myers-Squibb Italy provided an unrestricted research grant for the study conduction.Disclosure of Interests:None declared