ObjectivesThe aim of the present study was to describe demographic, clinical, and immunological characteristics of SLE patients with anti-La/SSB antibodies positive versus anti-La/SSB negative patients.MethodsRetrospective cross-sectional study, including all patients with SLE (≥4 ACR-1997 criteria) recruited in RELESSER registry. Sociodemographic, clinical, serological and comorbidities variables were collected. Anti-Ro-/La + patients were compared with the rest of the patients.ResultsIn a study involving 4219 systemic lupus erythematosus (SLE) patients, 44/3893 (1.1%) were found to be positive for isolated anti-La/SSB antibodies. The mean age was 33.77 years, with a majority being female (88.6%) and Caucasian (90.5%). The most frequent comorbidities were smoking (48.8%), dyslipidemia (47.7%), and arterial hypertension (31.8%). Photosensitivity and mucosal ulcers were more common in anti-Ro+/La + patients compared to anti-Ro+/La- and anti-Ro-/La- patients. Anti-Ro+/La + patients had a lower frequency of lupus nephritis compared to anti-Ro+/La- patients. A multivariable regression model, considering various confounding factors, was applied to compare anti-La/SSB positive patients with negative ones. Isolated anti-La/SSB positive patients showed a lower occurrence of lupus nephritis and a higher frequency of cardiac manifestations.ConclusionsThe study suggests that patients with isolated anti-La/SSB antibodies may have a unique clinical profile, with a potential protective effect against lupus nephritis but an increased likelihood of cardiac manifestations.

Background No data on agreement between patient perception, DORIS 2021 remission, LLDAS, or physician assessment is currently available. The aim is to compare the SLE activity perceived by the patient using the Patient Acceptable Symptom State (PASS) question with the global assessment of activity by the physician, and the definitions of LLDAS/DORIS2021. Methods A cross-sectional multicenter study involving SLE patients from seven Spanish Rheumatology Departments was conducted. The study applied DORIS 2021 remission criteria and LLDAS. Rheumatologists classified disease activity into five categories: remission, SACQ, low, moderate, or high. The patients were asked about their clinical SLE condition through the PASS question: 'Considering all the different ways your disease is affecting you, if you were to stay in this state for the next few months, do you consider your current state satisfactory?': PASS yes/PASS no. Statistical analysis included descriptive cross-sectional analysis and Cohen's kappa for agreement analysis. Results Among the 503 patients in the study (table 1), 386 (77.4%) reported an acceptable symptom state according to the PASS question. Mean patient global assessment (PtGA) was 29.62 (±24.38) on a scale of 0–100, while mean physician global assessment (PGA) was 0.46 (±0.59) on a scale of 0–3. A total of 236 (47.6%) patients met DORIS 2021 remission criteria, and 289 (59%) met LLDAS. According to the rheumatologists' categorical classification, 435 (86.8%) patients were in remission or low disease activity (table 2). Among PASS-affirmative patients, 65.5% met LLDAS and 57.9% met DORIS 2021 remission criteria, with lower PtGA (19.7) and PGA (0.29) scores. In the non-PASS group, 62.8% were not in LLDAS, and 87.6% did not meet DORIS 2021 remission criteria, with higher PtGA (58) and PGA (1) scores (table 3). The overall agreement between PASS and categorical classification was 82% with a Cohen's kappa of 0.43. Conclusions The majority of SLE patients reported an acceptable symptom state according to the PASS question, which aligns with the PtGA scale. Physicians' assessments also showed similarities with patient perspectives. However, notable differences were observed regarding remission/LLDAS criteria, indicating that while patient and physician perspectives align on subjective classification, variations exist concerning LLDAS and DORIS.

Introduction: Diffuse alveolar hemorrhage (DAH) is a rare complication with high mortality in patients with systemic lupus erythematosus (SLE). Early diagnosis and treatment are essential to improve patient prognosis. To determine the characteristics of patients with DAH and their mortality in a Spanish cohort of patients with SLE. Methods: Patients from the RELESSER (Spanish Society of Rheumatology Lupus Register) who had had at least one confirmed episode of DAH were included. Epidemiological, clinical, and laboratory characteristics were analyzed. Results: 4024 patients were included in the RELESSER register, 37 (0.9

Objective To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort.Methods We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance.Results A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777–0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48.Conclusions SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.

Background: The window of opportunity is well established in patients meeting the criteria for rheumatoid arthritis (RA) but is unclear in patients presenting with undifferentiated arthritis (UA). This study described changes in the management of patients with UA over 20 years in a registry of patients with recent-onset arthritis in a tertiary hospital in Madrid and analysed whether the concept of a window of opportunity could exist in these patients. Objectives: To describe the influence of the prescription of disease-modifying treatment (DMARD) on activity and disability in patients with UA over the 20 years of a registry of patients with recent-onset arthritis in a tertiary hospital in Madrid. Methods: All patients classified as UA[1] at the first visit of the registry from September 2001 to December 2019 were included. Demographic, clinical, analytical and treatment data were collected in a protocolised manner at four consecutive visits (baseline, 6 months, 1 and 2 years). To assess management changes, patients were grouped into four five-year periods (Q1 from 2001 to 2004, Q2 from 2005 to 2009, Q3 from 2010 to 2014 and Q4 from 2015 to 2019). Statistical analysis was performed with Stata 14.1 using the appropriate tests for bivariate analysis according to the type and distribution of variables. A multivariable model nested by patient and visit (xtgee command) was fitted to analyse the influence of the different variables on disease activity. All variables differing between five-year periods and those related to arthritis activity were included. Results: 309 patients were included in the analysis (77.7% female; age at disease onset 52 years [RIQ: 39-63]). The percentage of non-smokers decreased from the first to the last five-year period (67 vs 42.3%; p<0.0001). There was a trend towards an increase in seropositive cases (RF and anti-CCP) from the first to the last five-year period (p=0.013 and p=0.001, respectively). Time to first consultation and initiation of first DMARD decreased respectively from 6.6 (RIQ: 4.1-10.0) and 14.1 (RIC 5.2-31.5) months in the first five-year period to 3.5 (RIQ: 1.8-7.6) and 6.4 (RIC 2.8-18.4) months in the last five-year period (p=0.0019 and p=0.0001). Over the five-year periods, the use of methotrexate increased (16.7% more, p=0.004), and the use of antimalarials and sulfasalazine decreased (28.9% and 13.7% less, respectively, p=0.014). Disease activity progressively decreased, with a higher percentage of patients in remission at two years (25% more in the last five years p=0.046) and a progressive improvement in functionality, with a higher percentage of patients with mild disability in the last five-year period (26.3% more p=0.028) (Figures 1 and 2). After two years of follow-up, 45.4% of patients maintained the diagnosis of UA, 23.6% changed the diagnosis to RA, 4.6% to spondyloarthropathies and 26.4% to other processes, with no significant changes over time. Adjusting for all variables differing between the five-year periods (seropositivity, smoking and treatments), as well as those affecting disease activity (sex and age), a decrease in arthritis activity was observed in all five-year periods compared to the first (Q2 and Q4 p=0.032, Q3 p=0.003). Conclusion: Our preliminary results suggest that the therapeutic window of opportunity also exists in patients with UA by showing improvement in disease activity and functional capacity. REFERENCES: [1] Verpoort KN, van Dongen H, Allaart CF, Toes RE, Breedveld FC, Huizinga TW. Undifferentiated arthritis-disease course assessed in several inception cohorts. Clin Exp Rheumatol. 2004;22(5 Suppl 35): S12-7. Acknowledgements: NIL. Disclosure of Interests: None declared.

OBJECTIVES:To apply the lupus low disease activity state (LLDAS) definition within a large cohort of patients and to assess the agreement between the LLDAS and the physician's subjective evaluation of lupus activity. METHODS:We conducted a cross-sectional analysis of a prospective multicentre study of SLE patients. We applied the LLDAS and assessed whether there was agreement with the clinical status according to the physician's opinion. RESULTS:A total of 508 patients [92% women; mean age 50.4 years (s.d. 3.7)] were recruited and 304 (62.7%) patients were in the LLDAS. According to physician assessment, 430 (86.1%) patients were classified as remission or low activity. Overall agreement between both evaluations was 71.4% (95% CI: 70.1, 70.5) with a Cohen's κ of 0.3 [interquartile range (IQR) 0.22-0.37]. Most cases (96.1%) in the LLDAS were classified as remission or low activity by the expert. Of the patients who did not fulfil the LLDAS, 126 (70.4%) were classified as having remission/low disease activity. The main reasons for these discrepancies were the presence of new manifestations compared with the previous visit and a SLEDAI 2K score >4, mainly based on serological activity. CONCLUSIONS:Almost two-thirds of SLE patients were in the LLDAS. There was a fair correlation between the LLDAS and the physician's evaluation. This agreement improves for patients fulfilling the LLDAS criteria. The discordance between both at defining lupus low activity, the demonstrated association of the LLDAS with better outcomes and the fact that the LLDAS is more stringent than the physician's opinion imply that we should use the LLDAS as a treat-to-target goal.

Background The mortality in Systemic Lupus Erythematosus (SLE) varies largely across different countries most probably due to social, healthcare and ethnic differences. The contemporary cohorts continue to show higher mortality rates in SLE patients as compared with the general population 1,2. We need to identify demographic, clinical and serological predictors of mortality in SLE in our country, to improve the prognosis of SLE patients. Objectives To analyze the causes and identify predictive factors of mortality of SLE, and to assess the time evolution and chronological changes in Spain. Methods We performed a cross-sectional and retrospective study analyzing data from the RELESSER cohort (Spanish Registry of SLE of the Spanish Society of Rheumatology). Sociodemographic, clinical and serological variables, comorbidities and treatments, as well as indicators of disease activity, damage and severity were recorded. We excluded patients with lost information about the death variable and analyzed the differential features of deceased patients in comparisons with survivors through different time stages according to the date of diagnosis: until the 1980’s; the 1990’s and the first decade of the 21st century. Variables associated with mortality in univariate analysis were entered into different multivariate models to determine which ones were independently associated with the outcome of the disease in each decade. Results A total of 3665 patients were included, mostly caucasian female with similar general features regardless of the different time stages analyzed. The 18.4% until the 1980´s, the 5.97% in the 1990´s and up to 2.84% of the individuals in the first decade of the 21st century, had died. The main age of death was similar in the different groups, around 55-58 years old (Table 1). The vascular events were the leading cause of death until the 1980´s, while in the last two decades, were infections. The older age at diagnosis was predictor of mortality in our cohort. Neither gender nor delay in diagnosis was independently associated with mortality, with the exception of the female sex, which behaved as a protective factor until the 1980’s. The mortality predictors in our cohort were the presence of hypocomplementemia and organ damage until the 1980´s; thrombocytopenia, antiphospholipid syndrome and valve disease in the 1990´s; serositis, organ damage and depression in the first decade of the 21st century. Conversely, skin involvement was related to greater survival over the last two decades and comorbidities were associated with mortality in all periods of the study. The use of high doses of corticosteroids (>30mg/day) was predictor of mortality in each time stage, as well as the use of cyclophosphamide and rituximab from the year 2000. Antimalarial treatment was linked to improved survival in all the decades analyzed. Conclusion In the RELESSER cohort, the main cause of death in the last decades were infections. However, until the 1980´s, vascular events were predominant. Older age at diagnosis, the use of corticosteroids and comorbidities were associated with a significant increase in mortality in SLE, while antimalarial treatment was linked to improved survival. Data indicate that organ damage is a risk factor and skin involvement is a protective factor against mortality. Differentially, female sex until the 1980´s was independently associated with improved survival, and depression at the beginning of the 21st century was linked to mortality. Our results must be confirmed in prospective studies that minimize methodological limitations. References [1]Rees F, et al. Rheumatology (Oxford) 2016;55:854–60. [2]Jorge AM, et al. Rheumatology (Oxford) 2018;57:337–44 Acknowledgements Thank you to RELESSER researchers and collaborators, especially to profesor Jaime Calvo-Alén for having helped to develop this study. Disclosure of Interests None Declared.

Background Little is known about depression in SLE. To evaluate the prevalence of depression and associated factors in a large, multicenter SLE cohort (RELESSER-PROS). Methods Prospective longitudinal study of SLE patients answering positively to the depression question of the Lupus Impact Tracker (LIT) questionary (question number 7, LITQ7 'I was depressed') over 5 consecutive annual visits (V1 to V5). Self-perceived depression was answered from 0 ('none of the time') to 4 ('most of time'). Covariates with potential impact in depression were considered. Friedman test and GEE models were used. Results 1463 patients were included. Mean age 55 years, 90% female. Mean disease duration: 14 years. Fibromyalgia was present in 5.7%. Glucocorticoids use ranged from 49.4% to 57%, depending on the visit. SLEDAI ranged from 0 to 2 and SDI from 1 to 2. Prevalence of 'depression any time' was 89.9% and 'most of time' in 34.6%. Up to 26.5% answered to LITQ7 'depression most of time' in the five visits. 89.7% perceived themselves as depressed at least in 2 out of 5 visits. Only 6.9% of the patients with previous diagnosis of depression answered '0' ('none of the time') to LITQ7. SLEDAI, SDI, Charlson and glucocorticoids use showed statistically significative changes during the follow up. Patients with 'depression any time' developed more damage at V5 than patients without depression (p=0.009). In the GEE binomial analysis, fibromyalgia (OR 2.79), unemployment (OR 1.95) and glucocorticoids use (OR 1.88) were significantly associated with 'depression any time'. The best model displayed a significant association with fibromyalgia (OR 2.90) and glucocorticoids (OR 1.85). Neither SDI nor unemployment reached significance (table 1). Without entering glucocorticoids, SLEDAI turns significant in the model, suggesting collinearity. Conclusions The prevalence of self-perceived depression is high in SLE. Our study suggests causal relationship between glucocorticoids use, fibromyalgia and self-perceived depression.

Introduction: Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. Objective: To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. Methods: A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynae-cological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with com-plications during pregnancy. Results: A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. Conclusions: The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2-glycoprotein IgG/ IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes.

OBJECTIVES:To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). METHODS:Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. RESULTS:A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29-2.67) and more specifically CVD (HR 2.17, 1.41-3.33) and organic brain syndrome (HR 2.11, 1.19-3.74) accounted as independent prognostic factors for poor survival. CONCLUSION:The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates.

INTRODUCTION:Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS).MATERIALS AND METHODS:Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry.RESULTS:We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE (p < 0.001). SLE-APS patients showed higher rates of neuropsychiatric, cardiac, pulmonary, renal and ophthalmological manifestations than the other groups (p < 0.001). SLE-APS patients presented greater damage accrual with higher SLICC values (1.9 ± 2.2 in SLE-APS, 0.9 ± 1.4 in SLE-aPL and 1.1 ± 1.6 in SLE, p < 0.001) and more severe disease as defined by the Katz index (3 ± 1.8 in SLE-APS, 2.7 ± 1.7 in SLE-aPL and 2.6 ± 1.6 in SLE, p  < 0.001). SLE-APS patients showed higher mortality rates (p < 0.001).CONCLUSIONS:SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.