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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.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

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.

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

Objective To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting. Methods Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti–double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into “classical” (CLP) and “rheumatoid-like”; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0). Results Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P

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.

Objectives The aim was to determine whether assisted reproductive technologies (ARTs) confer additional risk in rheumatic patients (in terms of disease flare and fetal–maternal complications) and whether, if performed, their efficacy is affected by maternal disease. Methods Sixty infertile rheumatic women undergoing 111 ART cycles were included. Clinical pregnancy rate, live birth rate, maternal disease flares and maternal–fetal complications were recorded. Results One hundred and eleven ART cycles in 60 women were analysed. We reported 46 pregnancies (41.4%), 3 (3.1%) cases of ovarian hyperstimulation syndrome and no cases of thrombosis during stimulation, pregnancy and puerperium. One or more maternal complication was reported in 13 (30.2%) pregnancies, and fetal complications occurred in 11 fetuses (21.1%). The live birth rate was 98%, but we reported three (6%) perinatal deaths in the first days of life. During puerperium, we recorded one (2.5%) post-partum haemorrhage and one (2.5%) articular flare. Conclusion The safety and efficacy of the ARTs, demonstrated in the general population, seems to be confirmed also in rheumatic patients. No evidence was found to advise against their application, and the choice of therapy should be made depending on the patient’s risk profile, irrespective of whether the pregnancy is natural or artificial induced.

Background B- and T-cell hyper-activation is one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). SLE patients have a severe defect in the B cell tolerance check, resulting in high numbers of autoreactive mature naive B-cells (CD19 +CD27-IgD+) and of peripheral transitional B-cells (CD19 +38high24high). On the other hand, in patients with active SLE a reduced thymic output with a decreased number of recent thymic emigrants T-cells (RTE; CD4 +CD31+) was demonstrated, whereas repeated antigenic stimulation drives modifications in T-cells subpopulations, with enhanced differentiation into effector memory cells (CCR7-CD45RA-).1 Belimumab is a monoclonal antibody against soluble BLyS used in the treatment of severe SLE. Although B cells are the main target of this treatment, a BLyS-dependent T-cell activation pathway has also been demonstrated.2 However, few data are available on the effects of belimumab on circulating B- and T-cell subsets. Objectives The aim of this study was to characterise B and T-cell phenotype in a cohort of patients with SLE, and to analyse their modifications during belimumab therapy. Methods Phenotypic analysis of peripheral blood B and T lymphocyte subsets was made by flow-cytometry in 14 SLE patients before the first infusion of belimumab, and after 12 months of treatment. SLEDAI 2K-score was used to determine disease activity: a score ≥6 indicated high disease activity. Sex and age-matched healthy controls were enrolled for the comparisons. Results At baseline, SLE patients had lower numbers of B- (82 vs 153 cell/µl; p=0.05), T- CD4+ (365 vs 1131 cell/µl; p After treatment there was a decrease of total B lymphocytes (82 vs 19 cell/µl; p After 1 year therapy in the only 2 patients with persistent high disease activity the percentages of transitional B cells and unswitched memory cells were higher than in 7 patients in which an initially high disease activity decreased below SLEDAI=6 (9% vs 1%; p=0.03; and 29% vs 6%; p=0.04, respectively). Conclusions The effects of belimumab on B cell subpopulations are likely to be directly explained by the blockage of soluble BLyS. On the other hand, the effects on the phenotype of T cells are modest and it cannot be excluded that they are indirectly explained by the reduction of disease activity obtained through the therapy. The number of certain circulating B cell subsets might be a marker of response to treatment. References [1] Piantoni S, et al. Lupus2017. [2] Jacobi AM, et al. Arthritis Rheum2008. Disclosure of Interest None declared

Objective The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE). Methods Cohort study of consecutive pregnancies complicated with SLE during a period of 12 years is used. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight

Objective To investigate efficacy, safety and survival of belimumab and to identify predictors of drug response and drug discontinuation in patients with active SLE in clinical practice. Patients and methods Data of SLE patients, treated with belimumab, from 11 Italian prospective cohorts were analyzed. SLEDAI-2K, anti-dsDNA, C3, C4, prednisone daily dose, DAS-28, 24-h proteinuria, CLASIa (Cutaneous LE Disease Area and Severity Index Activity) were recorded at baseline and every 6 months. SLE Responder Index-4 (SRI-4) was calculated at 12 and 24 months. Demographic and clinical features and comorbidities were included in the univariate and multivariate analysis. Adverse events were recorded at each visit. Statistics was performed using the SPSS software. Results We studied 188 SLE patients, mean follow-up 17.5 ± 10.6 months. The most frequent manifestations, which required the use of belimumab, were polyarthritis (45.2%) and skin rashes (25.5%). SRI-4 was achieved by 77.0% and 68.7% of patients at 12 and 24-months. Independent predictors of 12-month response were SLEDAI-2K ≥ 10 (OR 40.46, p = 0.001) and polyarthritis (OR 12.64, p = 0.001) and of 24-month response were SLEDAI-2K ≥ 10 (OR 15.97, p = 0.008), polyarthritis (OR 32.36, p = 0.006), and prednisone ≥7.5 mg/day (OR 9.94, p = 0.026). We observed a low rate of severe adverse events. Fifty-eight patients (30.8%) discontinued belimumab after a mean follow-up of 10.4 ± 7.5 months. The drug survival was 86.9%, 76.9%, 69.4%, 67.1%, and 61.9% at 6, 12, 18, 24, and 30 months, respectively. No factors associated with drug discontinuation were found. Conclusion Belimumab is effective and safe when used in clinical practice setting.

Background Always more frequently rheumatic patients (pts) ask for Assisted Reproductive Technologies (ART) for infertility problems. The main concern is determined by the ovarian stimulation, associated with an increased risk of disease flare and thrombosis. Objectives To describe a case series of ART cycles in pts affected by rheumatic diseases, analyzing pregnacy rate and outcome, fetal-maternal complications and disease flares. Methods We included all the consecutive pts evaluated in the Pregnancy Clinic of 5 Italian Rheumatology Units after having performed ≥1 ART cycle from 1997 to 2016. Results We included 60 pts: infertility was primary (no previous spontaneous conception) in 68% of cases, idiopathic in 76.5%, of male origin in 8.3%, of female origin in 15%, mixed in 0.2%. One hundred and eleven ART cycles were performed: 13IUI, 44FIVET (3eterologous), 53ICSI (14eterologous), 1embryodonation. Antiphospholipid antibodies were positive in 23 (38.3%) pts and in 45 (40.5%) cycles. Procedures were unstimulated in 14 (12.6%) stimulated in 97 (59.5%) cases: with GnRH-Antagonist in 26 (26.8%), GnRH-agonist in 60 (61.8%), gonadotropins only in 7 (7.3%) and with clomiphene in 4 (4.1%) cases. We registered 3 (3%) cases of Ovarian Hyperstimulation Syndrome, all after Agonist protocol. Overall we observed 46 pregnancies, with a pregnancy rate of 38.7% for omologous procedures and of 55.5% for eterologous. No miscarriages were reported. Pregnancies ended with 35 single and 5 twin birth, 6 are still ongoing: we recorded 4 (8.9%) perinatal deaths: 1 baby died at birth for multiple malformations and 3 died in the first days of life for extreme prematurity. One or more fetal complications were reported in 11 (27.5%) pregnancies: 3PROM, 3IUGR, 3oligohydramnios, 4fetal malformation (2 severe, 1multiple and fatal). The mean age of the women suffering from fetal complications was significantly lower (p:0.03). One or more maternal complications were reported in 13 (32.5%) pregnancies: 4gestational diabetis, 2thrombocytopenia, 2pre-eclampsia, 2placenta previa, 1hypothyroidism, 1gestational hypertension, 1cholestasis of pregnancy. Disease Flares were reported in 5 (12.5%) pregnancies: 4 articular (2 in RA patients, 2 in SLE patients), 1haematological (in SLE patient, after spontaneous therapy discontinuation). No cases of thrombosis were reported.During puerperium: 1 (2.5%) post-partum hemorrage (no LMWH ongoing), 1 articular flare (2.5%). Additional informations are available in Table 1. Conclusions We didn9t found any good reasons to discourage ART performance in rheumatic pts: the safety seems to be high and the complications rate is in line with that reported in general population. An adequate prophylaxis during stimulation, pregnancy and puerperium seems to provide a good protection from thrombotic complications. Disclosure of Interest None declared

Background Rheumatic diseases (RD) predominantly affect young women during reproductive age. Pregnancy, contraception and family planning (FP) are crucial for the quality of life of these patients. Objectives We aimed to investigate 9women9s health9 through a self-reported questionnaire. Answers from patients with connective tissue diseases (CTD) vs chronic arthritis (CA) were compared. Methods 24 centres distributed the questionnaire (65 multiple-choice and 12 open-answer questions) to women with RD (18–45years) regularly attending their outpatient clinics. Results Answers were collected from 249 CTD vs 149 CA patients. Their desire to have children was influenced by RD in 40% of cases: half of them reduced the number of children they wanted (Table 1). 39% CA vs 29% CTD were afraid of being mother because of disability. 24% CTD vs. 18% CA had at least one miscarriage; 21% CTD vs. 2% CA had more than one. 31% CTD and 34% CA were never asked about their desire to have children. 61% CTD vs 70% CA received counselling about contraception, given by a gynaecologist (G) (58% vs 64%), rheumatologist (R) (22% vs 14%) or both (7% vs 9%). 60% in both groups received a counselling before pregnancy: 34% vs 39% from R and G, 14% vs 22% by R. This positively changed family planning in 64% vs 59%. We created a Knowledge Index (based on the average of the normalized performed scores on 6 key questions for different sections): 55% CTD patients vs 44% CA had a medium-high score. A higher score directly correlated with the desire to became pregnant and with a multidisciplinary counselling. Conclusions This survey suggested that CTD have a major impact on FP and family size, possibly mediated by the increased rate of miscarriages as compared to CA. Concerns about reproductive issues could be positively overcome by adequate counselling. Rheumatologists should implement the discussion about FP and the compatibility of drugs with pregnancy in the management of young women with RD, especially those with CTD for whom contraception and pregnancy have particular implications. Acknowledgements Statistical analysis supported by an unrestricted grant by UCB Pharma Thanks to Patients9 Associations and Participants Disclosure of Interest None declared

Objective To assess the prevalence of disease- and therapy-related complications and of the organ damage after a follow-up of 15 years or more in patients with primary antiphospholipid syndrome (PAPS). Methods Medical records of patients prospectively followed in our centre for at least 15 years were retrospectively reviewed. Results Thirty-five Caucasian patients (33 female, two male) with diagnosis of PAPS followed from 1984 to 2013 with a mean age at onset of 32 years (SD 8.17) and a median follow-up of 20.5 years (range 15–30) were included. The occurrence of systemic autoimmune disease was observed in 14% of patients. Haemorrhagic, infective and neoplastic events were recorded in 34%, 6% and 9% respectively. Organ damage was present in 20% of patients at the end of the follow-up (17% neurological and 3% renal) and was significantly associated with the occurrence of thrombotic events ( p: 0.027), particularly arterial ( p Conclusion During long-term follow-up of PAPS systemic autoimmunity is not unexpected. Organ damage progresses in a significant proportion of patients especially if they have suffered previous arterial events. Our study clearly shows the possible evolution of the disease and of organ damage, suggesting that optimal therapy and optimal prophylaxis of each PAPS patient should be carefully identified and strictly applied.

Introduction: Antiphospholipid syndrome (APS) is a systemic autoimmune disease representing the most frequent cause of acquired hypercoagulability and recurrent miscarriages. The disease has been known for at least 30 years, but its treatment is still a strongly debated topic for a number of reasons. First, it is difficult, if not impossible, to identify a univocal therapeutic regimen that will be effective for every patient, given the great clinical and serological heterogeneity of the disease. Second, it has been widely demonstrated that the positivity for antiphospholipid antibodies is not sufficient by itself to determine the clinical manifestations of the syndrome. Hence, the search for additional risk factors is needed in the critical analysis of the individual clinical setting in order to optimize the therapy. Third, a not negligible (notable) proportion of patients carry the resistant or recurrent form of the disease despite conventional treatments, showing the need for alternative therapeutic app...

Objective.To assess the longterm frequency of thrombotic recurrences, obstetrical complications, organ damage, severe comorbidities, and evolution toward connective tissue disease (CTD) in primary antiphospholipid syndrome (PAPS).Methods.Medical records of patients with PAPS followed in 6 centers for ≥ 15 years were retrospectively reviewed.Results.One hundred fifteen patients were studied: 88% women, followed between 1983 and 2014 with a mean (± SD) age at diagnosis of 33 (± 10) years. During a median followup of 18 years (range 15–30), 50 patients (44%) had at least a thrombotic event for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p = 0.002). A catastrophic antiphospholipid syndrome occurred in 6 patients (5%). The use of oral anticoagulants in patients with thrombotic onset did not appear to be protective against recurrences (p = 0.26). Fifty-two women had 87 pregnancies, successful in 78%. Twenty-nine percent of patients accrued functional damage. Damage was significantly associated with a thrombotic history (p = 0.004) and with arterial events (p < 0.001), especially stroke, but not with demographics, serology, or treatment. Twenty-four major bleeding episodes were recorded in 18 patients, all receiving anticoagulants. Severe infections affected 6 patients (5%), with 1 fatality. A solid cancer was diagnosed in 8 patients (7%). Altogether, 16 patients (14%) developed an autoimmune disease and 13 (11%) a full-blown picture of CTD.Conclusion.Despite therapy, a high proportion of patients experienced new thrombotic events and organ damage, while evolution toward CTD was infrequent.

The serious impact of the obstetric manifestations related to antiphospholipid syndrome (APS) can be understood by the fact that the disease was first described in patients with obstetric morbidity, in particular midtrimester foetal losses. The definition of obstetric APS includes different pathological manifestations: recurrent early pregnancy loss, foetal death, early severe preeclampsia, placental insufficiency, and/or intrauterine growth restriction and HELLP (haemolysis, elevated liver enzymes, and low platelets) syndrome. Nevertheless, the association between pregnancy loss or other pregnancy complications and antiphospholipid antibodies has yet not been completely defined. A very important aspect to consider in the management of patients with obstetric APS is the risk stratification: not all the clinical and the serological settings confer the same risk and consequently a tailored therapeutic approach is required. Success is the result of a careful surveillance conducted by a multidisciplinary team (obstetricians, rheumatologists, and neonatologists).

To investigate effectiveness and safety of belimumab in patients with active systemic lupus erythematosus (SLE) in a clinical practice setting.Sixty-seven patients with active SLE, mean ± SD age 39.3 ± 10.2 years, from 2 Italian prospective cohorts were treated with belimumab (10 mg/kg on day 0, 14, 28, and then every 28 days) added to background therapy. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the Disease Activity Score in 28 joints (DAS28), 24-hour proteinuria, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score, anti-double-stranded DNA (anti-dsDNA), C3 and C4 levels, and prednisone daily dose were recorded at baseline, month 3, 6, 9, 12, 18, and 24. Arthritis was subdivided into "classical" (CLP) and "rheumatoid-like"; skin manifestations into acute (ACLE), subacute (SCLE), and chronic. SLE flares, defined according to the SLEDAI Flare Index, were calculated before and after belimumab initiation. Adverse events were carefully evaluated during treatment. Statistics were performed by the SPSS package (version 21.0).Mean ± SD followup was 16.2 ± 9.5 months. Main refractory manifestations treated with belimumab were musculoskeletal (37.3%), mucocutaneous (22.4%), and renal (23.9%). SLEDAI-2K, prednisone daily dose, anti-dsDNA, DAS28, CLASI, and 24-hour proteinuria decreased during treatment. DAS28 score decreased in patients with polyarthritis (P 0.001), particularly in those with CLP (P 0.001), and CLASI decreased in patients with skin manifestation (P = 0.003), either ACLE (P = 0.051) or SCLE (P = 0.047). Flare rate was lower 1 and 2 years after belimumab initiation than in the periods before (P = 0.001). Belimumab was well-tolerated and no damage accrual was observed after initiation.Belimumab was effective and safe in a clinical practice setting; it decreased the number of flares and hindered damage progression in patients with active SLE.

Nowadays, most of the young women affected by Systemic Lupus Erythematosus (SLE) can carry out one or more pregnancies thanks to the improvement in treatment and the consequent reduction in morbidity and mortality. Pregnancy outcome in these women has also greatly improved in the last decades. A correct timing for pregnancy (tailored on disease activity and established during a preconception counselling), together with a tight monitoring during the three trimesters and the post-partum period (to timely identify and treat possible obstetric complications or maternal disease flares), as well as the concept of multidisciplinary management, are currently milestones of the management of pregnancy in SLE patients. Nevertheless, the increasing knowledge on the compatibility of drugs with pregnancy has allowed a better treatment of these patients, by choosing medications that control maternal disease activity without harming the foetus. However, particular attention and strict monitoring should be dedicated to SLE pregnant women in particular clinical settings: patients with lupus nephritis and patients with aPL positivity or Antiphospholipid syndrome, who are at higher risk for maternal and foetal complications, but also patients with anti-Ro/SSA and/or anti-La/SSB antibodies, because of the risk of neonatal lupus. A discussion on family planning, as well as counselling on contraception, should be part of the everyday-practice for physicians caring for SLE women during their reproductive age. Another issue is the possible reduction of fertility in these women, that can be due to different reasons. Consequently, the request for assisted reproduction techniques has been increasing in the last years, so that rheumatologists and gynaecologists should be prepared to counsel SLE patients also in this particular setting.

Autoimmune rheumatic diseases are chronic systemic conditions often affecting young women during their reproductive years, so that pregnancy is a major issue in their management. For a long time pregnancy has been discouraged in these women, mainly for two reasons: gestation could aggravate maternal disease and, vice versa, the disease could negatively influence the gestational outcome. The great improvement in the approach to pregnancy done in the past few decades has allowed a progressively increasing number of affected women to fulfill their family plan. Women should be informed about potential risks related to their disease, but they should also be reassured that a good pregnancy outcome is possible if conception occurs in a stable remission state, teratogenic medications have been properly withdrawn and "safe" drugs have been mantained to prevent disease flare. A brief excursus regarding the main issues regarding SLE/APS, Systemic Sclerosis and Systemic Vasculitis is provided, in the attempt to delineate the main risk factors for adverse pregnancy outcome, the onset of maternal complications and the role played by a close multi-specialistic monitoring.

Problem Cyclosporin A (CYS A) is an immunosuppressant agent administered in autoimmune diseases, and its use during pregnancy and lactation is a debated topic. Method of study The demographic characteristics, the activity of the underlying disease, and the onset of fetal–maternal complications have been investigated in 21 consecutive patients (2 RA, 14 SLE, 2 PA, 1 SjS, 1 DM, 1 Churg–Strauss vasculitis), treated with CYS A throughout 29 gestations. A subanalysis of the SLE group was performed. Results We recorded a live birth rate of 86.2%. The median gestational age at birth was 38.2 weeks. The prevalence of maternal–fetal complications showed no differences with general population. Disease flares appeared in 4% of patients during gestation and in 12% during puerperium. Conclusion We found no evidence justifying the suspension of CYS A when a pregnancy occurs. The drug does not appear to promote maternal–fetal complications and should be continued in patients who benefit from therapy. Data regarding breast-feeding during therapy are still scarce, but no evidence of toxicity has emerged.

Introduction L’evolution a long terme du syndrome des antiphospholipides primaire a ete peu decrite. Notre objectif etait d’evaluer les recidives thrombotiques, la survenue d’atteintes d’organes, de comorbidites, et le risque d’evolution vers une connectivite associee. Patients et methodes Etude retrospective des patients suivis au moins annuellement, pendant une duree d’au moins 15 ans dans l’un des 6 centres participants (hopitaux Pitie-Salpetriere et Cochin, Paris, France ; Brescia, Milan, Padua et Rome, Italie), pour un syndrome des antiphospholipides (defini selon les criteres de Sydney), sans connectivite definie associee au diagnostic. Resultats Cent quinze patients (88 % femmes) suivis entre 1983 et 2014, d’âge moyen (± SD) 33 ± 10 ans au diagnostic de syndrome des antiphospholipides primaire, et avec un suivi moyen de 19 ± 3,5 ans ont ete inclus. Cinquante et un patients (44 %) ont presente au moins un episode thrombotique au cours du suivi avec un total de 75 evenements et une incidence annuelle de 3,5 %. La survenue de thromboses etait plus frequente chez les patients avec antecedents de thrombose ( odds ratio [OR] : 4,8, IC95 % : 1,6–14,7 ; p = 0,002). Six des 31 patientes (19 %) ayant initialement un syndrome des antiphospholipides purement obstetrical ont ete atteinte d’une thrombose au cours du suivi. Six patients (5 %) sans antecedent de syndrome catastrophique des antiphospholipides, tous triples positifs pour la biologie antiphospholipides, ont presente un episode de syndrome catastrophique des antiphospholipides au cours du suivi. Cinquante-deux femmes ont eu 87 grossesses qui ont abouti a la naissance d’un enfant vivant dans 78 % des cas. Trente-quatre patients (29 %) avaient une sequelle fonctionnelle (principalement neurologique centrale, cardiaque, visuelle, renale, surrenalienne). La survenue de sequelles etait statistiquement associee aux antecedents de thromboses (OR : 13,9, IC95 % : 1,8–288,4 ; p = 0,004) et aux evenements arteriels (OR : 7,9, IC95 % : 2,7–24,3 ; p Conclusion Un nombre significatif de patients developpe de nouvelles thromboses et/ou des sequelles au cours du suivi prolonge.

To the Editor: We are pleased that our article1 has aroused interest from colleagues and we thank them for providing us valuable input for further analysis. We have considered the data presented by Monti, et al 2 in their Letter to the Editor regarding the good outcome obtained in a cohort of 21 patients after the switch from the intravenous (IV) to the subcutaneous (SC) formulation of abatacept (ABA). In their study, the risk of disease relapse appears to be lower than in our experience, even though about 40% of their patients presented moderate disease activity at the end of followup (6 mos after the switch). Within these, 21 patients (10%) showed an objective disease worsening. However, in general terms, the disease activity achieved during IV … Address correspondence to Dr. R. Reggia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. E-mail: rossella.reggia{at}gmail.com

Objective.Subcutaneous (SC) abatacept (ABA) is comparable to intravenous (IV) formulation in terms of efficacy and safety profile. Our work analyzed the switch to SC formulation from IV administration in patients with rheumatoid arthritis.Methods.Fifty-one patients treated with SC ABA were included. Clinical data were obtained from clinical charts.Results.Fourteen patients relapsed and needed to return to the IV administration. Neither clinical and laboratory features nor the previous therapies were identified as risk factors for SC formulation inefficacy. Disease activity decreased after the return to IV infusions.Conclusion.SC ABA showed a risk of relapse in 27% of cases. The reinsertion of the IV administration quickly reinstated disease control.

The aim of this article is to assess the predictive value of second trimester mean uterine artery Doppler pulsatility index (mUtA PI) for pregnancy complications in women with systemic lupus erythematosus (SLE).Cohort study of consecutive pregnancies complicated with SLE during a period of 12 years is used. SLE diagnosis was made before pregnancy. mUtA PI was measured between 23 + 0 and 26 + 6 weeks' gestation. Pregnancy and neonatal outcomes were collected. Small for gestational age (SGA) was defined as birth weight10th percentile. Adverse pregnancy outcome (APO) was defined as one of the following: pre-eclampsia (PE), SGA, placental abruption, stillbirth, or neonatal death. Differential diagnosis between PE and renal flare was made according to SLE-disease activity index.There are 70 pregnancies in 64 women. PE was observed in four cases (6%), SGA in five cases (7%), and APO in seven cases (10%). mUtA PI showed a sensitivity and a specificity of 1.0 (95% CI 0.5-1.0) and 1.0 (95% CI 0.95-1.0) for PE, 0.40 (95% CI 0.12-0.77) and 0.97 (95% CI 0.89-0.99) for SGA, and 0.57 (95% CI 0.25-0.84) and 1.0 (95% CI 0.94-1.0) for APO, respectively.Our findings suggest that uterine artery Doppler is confirmed to be a high sensitivity and a high specificity test for predicting PE even in SLE patients.

IgA antiphospholipid antibodies (aPL) are not currently recognized as formal laboratory criteria for the Antiphospholipid Syndrome (APS). This is mainly due to methodological issues (different study designs, use of various non-standardized IgA assays). However, there are experimental data showing the pathogenic role of IgA anti-cardiolipin antibodies (aCL) and IgA anti-β2glycoprotein I antibodies (anti-β2GPI). Isolated IgA aCL are not very common, therefore their testing could be useful in the case of strong suspicion of APS but negative results for other aPL tests. IgA anti-β2GPI seem to be the most prevalent isotype in patients with Systemic Lupus Erythematosus (SLE), with a significant association with thrombotic events. Such a clinical relevance has been recently recognized by the inclusion of these autoantibodies among the aPL tests in the novel SLICC classification criteria for SLE. Emerging interest has been raised by IgA anti-β2GPI against domain 4/5 as a novel subgroup of clinically relevant aPL.

Background Data on the long-term outcome in primary antiphospholipid syndrome (PAPS) patients are still very limited. Objectives To assess the long-term frequency of recurrences, organ damage, severe comorbidities, mortality and evolution in connective tissue disease (CTD) in PAPS patients. Methods Medical records of PAPS patients followed in 6 centers for ≥15 years were retrospectively reviewed. Chi square for categorical and Student t test for continuous variables were used. P Results One hundred and fifteen patients (88% females) followed between 1983 and 2014 with a mean age at diagnosis of 33 (±10) years and mean follow-up of 19 (±3.5) years were studied. Fifty-one patients (44%) had at least a thrombotic event during follow-up for a total of 75 events and an annual incidence of 3.5%. Thromboses were more frequent in patients with previous thrombotic history (p:0.002,OR:4.8, 95%CI:1.6–14.7). There was a tendency towards anticoagulant treatment being not protective against recurrences (p:0.063). Six patients (5%) had a catastrophic event. Fifty-two women had 87 pregnancies, successful in 78% of cases. Twenty-nine percent of patients had functional damage. Damage was significantly associated with a thrombotic history (p:0.004,OR:13.9,95%CI:1.8–288.4) and to arterial events (p Conclusions Despite therapy, a high proportion of patients experienced new thrombotic events,while pregnancy outcome was significantly improved. Organ damage developed in a significant proportion of patients and was associated with arterial events. The risk of evolution in CTD has to be considered. Disclosure of Interest None declared

Objective. To evaluate the association between serum complement levels (C3 and C4) and obstetric complications. Methods. Fifty-seven pregnancies in primary APS (PAPS) patients were compared with 49 pregnancies in patients with UCTD and SS. A group of 175 healthy pregnant women were studied to calculate a normality range for C3 and C4 during pregnancy. Such a range was applied to define hypocomplementaemia in PAPS and UCTD/SS. Results. Both groups of patients (PAPS and UCTD/SS) showed significantly lower levels of C3 and C4 in each trimester as compared with healthy women; conversely, no significant difference was found between PAPS and UCTD/SS. Comparing PAPS pregnancies with and without complications, no difference was found in the prevalence of low C3 or low C4. Conclusion. No association was found between hypocomplementaemia and obstetric complications in PAPS. However, both cases of pre-eclampsia were characterized by low C3 throughout pregnancy. There is evidence that the complement system is a contributor to the mechanisms of aPL-mediated damage, but its predictive role on the final pregnancy outcome does not seem to be of major impact.

Multidisciplinary approach and patient counselling have been the key points in the improvement of the management of pregnancy in women with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Most of these women can have successful pregnancy when thoroughly informed and instructed on several different issues. Disease activity should be in stable remission prior to pregnancy in order to reduce the chance for flare during pregnancy. To this purpose, medications must be modulated: “safe” drugs should be continued throughout pregnancy, embryotoxic/foetotoxic drugs should be withdrawn timely, and beneficial drugs such as low dose aspirin and heparin should be added for prophylaxis of maternal and foetal outcome, especially in the presence of antiphospholipid antibodies. The safety profile of anti-rheumatic drugs during pregnancy and breastfeeding should be kept constantly updated, as new data from inadvertent exposure accumulates and new drugs (especially biological agents) are available. Patients may carry autoantibodies that can negatively affect the baby, being neonatal lupus the prototypical case of passively acquired autoimmunity. Research has been greatly active in this field and more information on risk stratification and management are now available for counselling. The effect of both autoantibodies and drug exposure has been evaluated in the offspring: some concerns about learning disabilities have been raised, but these are treatable conditions that are likely to be overcome. To counsel a woman with SLE/APS during childbearing age means also to deal with contraception. Despite the “preferred choice” – combined oral contraceptive – may not be suitable for most of the patients, other options are available and should be offered and discussed with the patient. Fertility is not generally affected in SLE/APS patients, but those cases who require assisted reproduction techniques should be carefully evaluated and managed.

Rheumatic diseases can affect women during their childbearing age. Therefore, physicians should introduce a discussion with the patients about pregnancy and its problems. Lupus pregnancies can be successful, even in patients with renal disease, when planned in remission state; the use of low dose aspirin was shown to be an independent predictor of good outcome, so it can be suggested as a preventive measure. Pregnancies in women with Antiphospholipid Syndrome can fail even if properly treated, especially when associated with a systemic autoimmune disease, a history of both thrombosis and pregnancy morbidity, and a triple positivity of antiphospholipid antibody assays. Women with systemic sclerosis have generally a good obstetric outcome, except for an increase rate of preterm deliveries. Severe disease complications were sometimes reported, but their relationship with gestation is not clear yet. Although data on human pregnancy are still preliminary, anti-TNF agents are classified as non teratogens in contrast to methotrexate and leflunomide. So women affected by aggressive chronic arthritis may be treated with anti-TNF in the pre-conceptional period, discontinuing the drug as soon as pregnancy starts. In order to increase maternal compliance and cope with difficult cases, a multidisciplinary team (rheumatologists/internists, obstetricians and neonatologists) should take care of patients during pregnancy.

Background Anti-TNFalfa agents have been used to control disease activity of patients with Chronic Arthritides (Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosis Spondilitis) during the wash-out period of teratogenic drugs. Patients with flares during pregnancy may also receive anti-TNFalfa agents during the 2nd-3rd trimester. Objectives To investigate the health and developmental conditions of children who were exposed in utero to anti-TNFalfa agents and to compare them with non-exposed children born to women with the same disease. Methods An ad-hoc created questionnaire was submitted to women who were followed during pregnancy by a multidisciplinary team (rheumatologist, gynaecologist, neonatologist). Data on birth, lactation, weaning, growth parameters, developmental milestones, vaccinations and disease conditions were collected for the first 24 months of life. Results The characteristics of 24 cases (9 male, 15 female) (20 exposed to etanercept, 3 to adalimumab, 1 to certolizumab) and 24 controls (12 M, 12 F) are reported in the table (median value, interquartile range). Eighteen children were exposed during the first trimester (discontinuation of anti-TNFalfa agent at positive pregnancy index), while six during the 2nd-3rd trimester (discontinuation at 34th-37th week). Both cases and controls underwent vaccinations without any severe complications. Vaccinations were protective. Only one child developed chicken-pox despite vaccination (exposure to etanercept in the 1st trimester, until the positive pregnancy index). Conclusions No differences in birth parameters, congenital malformations, and developmental steps in the first 24 months of life were found between cases and controls. Growth parameters were within the curves of the general population. Cases received more vaccinations than controls. This may be due to the feeling by either parents or paediatricians that these children exposed to immunosuppressive agents could be more susceptible to infectious diseases. No relevant infectious diseases nor post-vaccine complications were noted in the 6 children exposed to anti-TNFalfa during the 2nd-3rd trimester of gestation. Neurodevelopmental problems were recorded in 2 children: an autism spectrum disorder in one male exposed to etanercept in the 2nd-3rd trimester and a language delay in a male control. Globally, the long-term follow-up of children supports the safety of use of anti-TNFalfa agents, either preconceptionally or during the 2nd-3rd trimester of pregnancy. References Ostensen, M. (2014) Safety issues of biologics in pregnant patients with rheumatic diseases, Academy of Sciences, New York. Disclosure of Interest None declared

Background Antiphospholipid antibodies (aPL) are risk factors for adverse pregnancy outcome (APO). Still debated is the prognostic role of the aPL profile, defined as the combination of the 3 criteria tests for aPL (LA: Lupus Anticoagulant; aCL: anti-cardiolipin; aB2GPI: anti-beta2glycoprotein I) and the antibody titer (low vs. medium-high) of aCL and aB2GPI. Objectives To determine the association between the aPL profile and the occurrence of APO in prospectively followed, treated pregnancies. Methods 217 pregnancies in 154 women were prospectively followed by a multidisciplinary team of rheumatologists and obstetricians in a single center between 1985 and 2014. Patients were classified as Primary Antiphospholipid Syndrome (PAPS) according to the revised criteria. Patients not fulfilling the criteria, were defined as either non-criteria PAPS or aPL carriers, according to their clinical history and/or aPL status. Patients with concomitant systemic autoimmune diseases were excluded. Data were retrospectively collected and analyzed by aPL profile categories. APO was defined as at least one of the following: miscarriage (before 10th week), fetal death (beyond 10th week), severe preterm delivery (before 34th week) with or without preeclampsia (PE), HELLP syndrome or perinatal death. Statistical analysis was performed with Chi-square with Yates9 correction (p-value significant Results The serological profile (triple, double, single aPL positivity) and diagnostic classification of the 217 pregnancies is shown in Table 1. APO occurred in 33 (15%) pregnancies: 14 (42%) in triple positive, 5 (15%) in double positive, and 14 (42%) in single positive patients. Fifteen APO (45%) occurred in LA negative pregnancies. Triple aPL positivity was significantly associated with APO in comparison with double + single positivity (χ2=5.61, p=0.006). In order to assess the role of antibody titers, the analysis was restricted to pregnancies positive for each single aPL test (IgG/IgM aCL, IgG/IgM aB2GPI). No difference in the frequency of APO was observed between pregnancies with low vs. medium-high titer for IgG aCL, IgM aCL, and IgM aB2GPI. Medium-high titers of IgG aB2GPI were associated with APO in comparison with low titers, respectively 17 pregnancies (27%) vs 4 pregnancies (8%) (χ2=5.20, p=0.02). Among these 17 pregnancies with medium/high titers, 13 (76%) were triple aPL positive. Conclusions Patients with triple aPL positivity seem to be at higher risk for APO despite conventional treatment. aCL and aBGPI titers do not seem to be associated with APO, therefore patients in our cohort with low titers cannot be considered at “low risk” for obstetric events, although being treated. Disclosure of Interest None declared

Background Abatacept is a selective T cell costimulation modulator indicated for moderately to severely active Rheumatoid Arthritis (RA). Since August 2013 the new subcutaneous (sc) formulation is available in Italy. Itconsists in a fixed dose of 125 mg of the drug, administered once weekly. Objectives To retrospectively analyze the clinical response of a cohort of patients (pts) with RA treated with monthly iv infusion who converted to the sc formulation. Methods We included 49 pts with RA, converted from iv to sc Abatacept from October 2013 to April 2014. We divided them into two groups, depending on their need to switch back to the iv administration for the appearance of a disease flare, defined as a numeric increase in DAS28.The main clinical and serological features of the two groups have been compared using the Chi-square, T-test or the Mann-Whitney test. Results Fifteen pts (30.6%) returned to the iv administration due to a disease flare (mean DAS28: 4.8 vs 2.1, p Conclusions Although the safety profile of the sc Abatacept seems to confirm the previously obtained data with the iv use of the drug, a high rate of our patients complained a reduced efficacy, also confirmed by the subanalysis of the objective components of the DAS28 index (CRP values and joints involvement). However this study was retrospective and there were no informations on compliance to the sc formulation in pts who flared. We have failed to identify clear risk factors that may help toward the selection of pts to which propose the formulation switch, however, if an arthritic flare occurs, the return to the iv administration seems to ensure a good control of the disease again. Nevertheless, the switch failure seems to predict a reduced persistence of abatacept efficacy during time. References Rakieh C, Conaghan PG. Comparative clinical utility of once-weekly subcutaneous abatacept in the management of rheumatoid arthritis. Ther Clin Risk Manag. 2014;10:313-20. Wells AF, Jodat N, Schiff M. A critical evaluation of the role of subcutaneous abatacept in the treatment of rheumatoid arthritis: patient considerations. Biologics. 2014;8:41-55.Review. Disclosure of Interest None declared

Background Data on the long-term outcome in primary antiphospholipid syndrome (PAPS) patients (pt) are still very limited. Objectives To assess the prevalence of recurrences,organ damage,severe comorbidities (infections, hemorrhages,cancers),mortality,evolution in connective tissue disease (CTD), in long-standing PAPS.To compare non criteria manifestations,serological alterations,cardiovascular risk factors and therapy between onset and follow-up. Methods Medical records of PAPS pt followed in 6 centers for ≥15 years were retrospectively reviewed.Chi square for categorical and Student t test for continuous variables were used.P Results One hundred and sixteen pt (88% females) with PAPS followed between 1983 and 2014 with mean age at diagnosis of 33 (±10) and mean follow-up of 19 years (±5) were studied.Fifty-one pt (44%) had at least a thrombotic event during follow-up. Thromboses were more frequent in patients with previous thrombotic history (p:0.003,OR:4.68, 95%CI:1.6-14.3) and anticoagulant treatment was not protective against recurrences (p:not significant).Six pt (5%) had a catastrophic event. Fifty-two women had 87 pregnancies, that were successful in 76% of cases. Thirty-one (27%) pt had organ damage (permanent loss of function) in at least one system (15% neurological,3% renal,5% cardiac,4% ocular, 1% peripheral vascular,1% osteoarticular,1% gastrointestinal).Damage was significantly associated to a thrombotic history (p:0.008,OR:11.8,95%CI:1.6-245.3) and to arterial events (p Conclusions Despite therapy, a high proportion of pt experienced new thrombotic events,while pregnancy outcome was significantly improved.Organ damage developed in a significant proportion of pt and was associated with arterial events. Evolution in CTD was not common but occurred during follow-up.PAPS is a disease of young people characterized by relevant morbidity and premature mortality. Disclosure of Interest None declared

Background While acute manifestations related to APS are well known and their treatment is quite standardized, informations on the long-term outcome in affected patients are still very limited 1–3 , even though the disease has been known for at least 30 years. Objectives Primary objective was to assess the prevalence of thrombotic and obstetrical recurrences, severe complications, organ damage (and related risk factors) and mortality in PAPS with long-standing disease. We also compared systemic involvement, serological alterations, cardiovascular risk factors and therapy between the onset and the follow-up. Methods Medical records of patients with PAPS regularly and prospectively followed in our center for at least 15 years were retrospectively reviewed. Fisher9s exact test for categorical variables was used. P values Results Thirty-five Caucasian patients (33 female and 2 male) with diagnosis of PAPS (Miyakis et al 2006) followed from 1984 to 2013 with a mean age at onset of 32 years (SD 8.17) and a median follow-up of 20.5 years (range 15-30) were included in this analysis. A thrombotic event appeared in 28% of patients during follow up (venous in 50%, arterial in 40% and both in 10%). Nineteen patients (57%) had a total of 28 pregnancies, that was successful in 75% of cases. No CAPS were observed during follow-up. Hemorrhagic, infective, neoplastic events were recorded in 34%, 6% and 9% of patients respectively. Organ damage was present in 20% of patients at the end of follow-up (17% neurological deficit and 3% chronic kidney failure)and was statistically significantly associated to a previous thrombotic history (p:0.027) and in particular to a previous arterial thrombosis (p Conclusions Despite therapy, a high proportion of patients experiences new thrombotic events and severe complications, while pregnancy outcome seems to be quite good. Organ damage progresses in a significant proportion of patients and it is associated with previous arterial events. Unluckily PAPS can be mortal. A strict control of cardiovascular risk factors and effective treatment are needed to improve the long term outcome. References Erkan D, Yazici Y, Sobel R, Lockshin MD. Primary antiphospholipid syndrome: functional outcome after 10 years. J Rheumatol. 2000;27:2817-21 Cervera R, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Kiss E, et al. Morbidity and mortality in the Antiphospholipid syndrome during a 5-year period: A multicenter prospective study of 1000 patients. Ann Rheum Dis 2009;68:1428-32 Grika EP, Ziakas PD, Zintzaras E, Moutsopoulos HM, Vlachoyiannopoulos PG. Morbidity, mortality, and organ damage in patients with Antiphospholipid syndrome. J Rheumatol. 2012; 39:516-23. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.1759

Background Cyclosporin-A (CYS-A) is an immunosuppressant agent widely used in the context of anti-rejection therapy. In Rheumatology it’s indicated for Rheumatoid Arthritis (RA) and Psoriasic Arthritis (PA), but it’s also administered to control other connective tissue diseases like Systemic Lupus Eritematosus (SLE) and Dermatomyositis (DM) and in patients suffering from vasculitis. These diseases often occur in fertile women, therefore, in recent years, the compatibility of the drug with pregnancy has been largely debated. FDA classifies CYS-A in class C, since there are no conclusive data about it’s safety and not recommended breastfeeding during therapy, even though several registries and retrospective studies seem to demonstrate its safety [1,2]. Most of the available data derive from exposed pregnancies in transplanted women [3] and no studies have shown adverse effects on newborns [4]. Objectives To analyze a series of patients suffering from autoimmune diseases, treated with CYS-A during pregnancy and to highlight any related maternal-fetal complications. Methods 25 pregnancies in 19 consecutive patients treated with CYS-A throughout gestation was analyzed, focusing on demographic characteristics, underlying disease activity and the onset of maternal and/or fetal complications. Results At the time of pregnancy, patients had an average age of 32.2 years and underlying diseases in stable remission. They suffered from RA (n=2), PA (n=2), SLE (n=13, 1with associated Kikuchi disease), Sjogren Syndrome (n=1), DM (n=1). Therapy was made of CYS-A, 3mg/kg (tapered to suspension before delivery in 5 patients: 20%), low-medium dosage steroids(n=20: 80%), aspirine (n=22: 88%), hydroxychloroquine (n=17: 68%), azathioprine (n=1: 4%) and low molecule weight heparin (n=4: 16%). We had 20 full-term pregnancies (80%), with a mean gestational age of 38weeks, 1 is still ongoing.1 PROM (4.8%) and 2 IUGR (10%), both evolved into SGA babies. 3 Spontaneous Abortions (12%)and 1 voluntary abruption because of the finding of Turner’s Syndrome and cystic hygroma (4%).11 pregnancies (55%) resulted in natural delivery, 9 (45%) in caesarean section. Newborns presented a mean birth-weight of 2857g and they all had normal apgar scores. We found 2 (10%) maternal disease flares during gestation and 2 (10%) in puerperium. 2 cases of gestational hypertension (1 of new onset) and 2 (10%) elevations of pre-existing proteinuria. Conclusions According to existing data we found no evidences justifying the suspension of CYS-A when a pregnancy occurs. The drug does not appear to increase maternal-fetal complications comparing with general population(PROM:4.8%vs10%, IUGR:10%vs4-8%, Gestational hypertension:10%vs4-10%)and it should be continued in patients who benefit from therapy. When possible, the drug should be tapered to suspension to allow breastfeeding. References Cimaz R, Meregalli E, Biggioggero M, et al:Alterations in the immune system of children from mothers treated with immunosuppressive agents during pregnancy. ToxicolLett2004,149:155-162. Ostensen M, Khamashta M, Lockshin M, et al:Anti-inflammatory and immunosuppressive drugs and reproduction. ArthritisResTher2006, 8:209. McKay DB, Adams PL, Bumgardner GL, et al:Reproduction and pregnancy in transplant recipients:current practices. ProgTransplant.2006;16:127-32. Al-Khader AA, Basri N, Al-Ghamdi, et al:Pregnanciesin renal transplant recipients, with a focus on babies. AnnTransplant.2004;9:65-7. Disclosure of Interest None Declared

ObjectiveTo analyze complement level variations in systemic lupus erythematosus (SLE) pregnancies, focusing on disease flares and obstetric complications.MethodsSLE pregnancies prospectively followed by multidisciplinary teams from 1987 to 2018 in 2 Italian rheumatology centers were retrospectively analyzed. As reference, pregnancy-modified ranges of normal levels of C3 and C4 were derived from 175 pregnancies from the general obstetric population (GOP), as previously described by our group.ResultsTwo hundred forty-six pregnancies in 172 patients with SLE were analyzed. Eighty-nine percent were live births. Thirty-five flares were recorded in 30 pregnancies (12.2%) and obstetric complications occurred in 47 pregnancies (19.1%) including 27 pregnancy losses, 11 severely preterm births (2 resulting in perinatal death), and 15 hypertensive disorders. C3 and C4 levels were higher in the GOP than in patients with SLE, at any time point. C3 and C4 levels progressively increased during pregnancy in both GOP and SLE pregnancies without flare and obstetric complications, whereas this physiological increase was not observed in pregnancies with flares or obstetric complications. A significantly higher frequency of low C4 was found in pregnancies with flares (at preconception and in each trimester) and preterm births (at preconception). In multivariate analysis, low C4 at preconception was associated with flares (odds ratio 13.81, 95% CI 3.10-61.43,P< 0.001).ConclusionLow C4 at preconception was found to be an independent risk factor for SLE flare during pregnancy. Not only C3 and C4 levels but also their variations should be observed, as their failure to increase can be useful to predict risk of complications and suggest closer monitoring.