BackgroundSystemic lupus erythematosus (SLE) SLE often mimics the symptoms of other diseases, and the interval between symptom onset and diagnosis remains long in these patients.ObjectivesTo examine the variables associated with a delay to diagnosis and their impact in damage accrual and mortality in patients with SLE.MethodsGLADEL a multi-ethnic, multi-national Latin-American SLE inception cohort was studied. Patients were recruited based on the physicians’ diagnosis but 97% fulfilled the ACR criteria. Delay to diagnosis was defined as ≥6 months from the first ACR criterion to SLE diagnosis. Socio-demographic, clinical/laboratory, disease activity, damage and mortality were compared using descriptive statistical tests. Multivariable Cox regression (HR) model with damage accrual and mortality as the end points were performed.ResultsOf the 1437 included in this analysis, the median delay to diagnosis was 5.9 months (Q1-Q3 2.4–16.1) and 721 (50.2%) had ≥6 months delay in SLE diagnosis. Patients with delay in diagnosis were more frequently of female gender, older age at diagnosis, mestizo ethnicity and without medical insurance. The characteristics of patients according to delay in diagnosis are depicted in Table 1. Delay to diagnosis did not impact on disease outcome: damage accrual [HR 1.21 (IC 95% 0.78-1.88; p=0.39)] and mortality [HR 1.30, CI 95% 0.84-2.01; p= 0.24)], after adjusting for age at SLE diagnosis, gender, ethnicity and socioeconomic status.ConclusionIn the GLADEL cohort, delay to diagnosis was associated to sex, age, thrombosis, sicca syndrome, cutaneous and neurological involvement. Furthermore, delay to diagnosis had no apparent negative impact on disease outcome (damage accrual and mortality). Early referral when there are suspicious clinical manifestations of SLE is crucial to reduce the diagnostic delay.Table 1.Comparison between the two patient groups in relation at the time to SLE diagnosis.VariableTime to SLE Diagnosis< 6 months (n=716)≥ 6 months (n=721)p valueAge at diagnosis, years(median, IQR)25.6 (16.2)30.4 (15.6)<0.001Follow-up time, months(median, IQR)54(44.1)53(48.6)0.302Female, n %628 (87.7)662 (91.8)0.010Ethnicity, n %MestizoAfrican Latin AmericansCaucasian306 (42.7)116 (16.2)294 (41.1)339 (47.0)70 (9.71)312 (43.3)0.001Education level, years, n%0-7 years8-12 years>12 years216 (30.2)329 (45.9)171 (23.9)237 (32.9)320 (44.4)164 (22.7)0.541Have medical insurance*(13), n%606 (84.6)573 (79.5)0.020Socioeconomic status, n%LowMiddleHigh436 (61.2)204 (28.7)72 (10.1)437 (60.6)208 (28.8)76 (10.6)0.955Clinical manifestations§, n%Malar rashDiscoid lupusPhotosensitivityOral ulcersArthritis/ ArthralgiaPleuritisPericarditisPsychosis/ seizuresHematological disorderProteinuria/ cylindruriaFeverLymphadenopathyLivedo reticularisRaynaud’s phenomenonSicca syndromeCardiac tamponadeVascular thrombosisStroke (ischemic)Pulmonary involvementPeritoneal serositis376 (52.5)70 (9.8)327 (45.7)239 (33.4)611 (85.3)124 (17.3)92 (12.9)39 (5.5)372 (52.0)254 (35.5)403 (56.3)97 (13.6)32 (4.5)125 (17.5)21 (2.9)6 (0.8)14 (2.0)4 (0.6)24 (3.4)9 (1.3)186 (25.8)72 (10.0)379 (52.6)226 (31.4)634 (87.9)104 (14.4)61 (8.5)60 (8.3)403 (55.9)202 (28.0)303 (42.0)67 (9.3)52 (7.2)190 (26.4)52 (7.2)0 (0.0)28 (3.9)12 (1.7)14 (1.9)1 (0.1)0.9000.8940.0090.4090.1480.1330.0070.0310.1340.002<0.0010.0110.027<0.0010.0020.0140.0300.0460.0960.011Hypocomplementemia§, n%487 (68.0)385 (53.4)<0.001Antiphospholipid antibodies§, n%363 (50.7)375 (52)0.795SLEDAI† at diagnosis, median (RIQ)*(257)12.0 (10.0)9.0 (9.0)<0.001SDI at the last visit‡ ≥ 1494 (69.0)484 (67.1)0.448Death during follow-up, n%39 (5.5)45 (6.2)0.521SD (standard deviation); IQR (Interquartile range); § Before SLE diagnosis; † Systemic Lupus Erythematosus Disease Activity Index; ‡ SDI (Systemic Lupus International Collaborating Clinics) Damage Index;*(Missing data)REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundIn Argentina we have witnessed two COVID 19 waves between 2020 and 2021. The first wave occurred during the spring of 2020 and it was related to the wild type of the virus, the second occurred during the fall/winter of 2021 when the gamma variant showed a clear predominance. During the first wave, patient with rheumatic diseases showed a higher frequency of hospitalization and mortality (4% vs 0.26%) when compared to the general population1; at that time, however, vaccination was not yet available.ObjectivesTo compare sociodemographic and disease characteristics, course and outcomes of SARS-CoV-2 infection in patients with immune-mediated/autoinflammatory diseases (IMADs) during the first and second waves in Argentina.MethodsSAR-COVID is a national, multicenter, longitudinal and observational registry, in which patients ≥18 years of age, with a diagnosis of a rheumatic disease who had confirmed SARS-CoV-2 infection (RT-PCR or positive serology) were consecutively included since August 2020. For the purpose of this report, only patients with IMADs who had SARS-CoV-2 infection during the first wave (defined as cases occurred between March 2020 and March 2021) and the second wave (cases occurred between April and August 2021) were examined. Sociodemographic characteristics, disease diagnosis and activity, comorbidities, immunosuppressive treatment and COVID 19 clinical characteristics, complications and outcomes: hospitalization, intensive care unit (ICU) admission, use of mechanical ventilation and death were compared among groups. Descriptive statistical analysis was performed. Variables were compared with Chi squared test and Student T test or Mann Whitney test. Multivariable logistic regression models with forward and backward selection method, using hospitalization, ICU admission and death as dependent variables were carried out.ResultsA total of 1777 patients were included, 1342 from the first wave and 435 of the second one. Patients had a mean (SD) age of 50.7 (14.2) years and 81% were female. Both groups of patients were similar in terms of socio-demographic features, disease diagnosis, disease activity, the use of glucocorticoids ≥ 10 mg/day and the immunosuppressive drugs (Table 1 below). Patients infected during the first wave have higher frequency of comorbidities (49% vs 41%; p= 0.004). Hospitalizations due to COVID 19 (31% vs 20%; p <0.001) and ICU admissions (9% vs 5%; p= 0.009) were higher during the first wave. No differences in the use of mechanical ventilation (16% vs 16%; p= 0.97) nor in the mortality rate (5% vs 4%; p= 0.41) were observed. In the multivariable analysis, after adjusting for demographics, clinical features and immunosuppressive treatment, patients infected during the second wave were 40% less likely to be hospitalized (OR= 0.6, IC95% 0.4-0.8) and to be admitted to the ICU (OR= 0.6, IC95% 0.3-0.9).Table 1.Variable (% or Mean – SD)First wave(n=1342)Second wave(n=435)p ValueFemale gender81800.7Age (years)51.0 (14.5)50.0 (13.3)0.2Disease diagnosis Rheumatoid arthritis46461 Ankylosing spondylitis10110.8 Systemic lupus erythematosus171850.9 Systemic Scleroderma551 Sjögren´s syndrome650.7 Inflammatory myopathies330.5 Vasculitis430.4Disease activity High430.5Use of immune modulatorsDMARDcs53560.2DMARDts460.1DMARDb82821Use of glucocorticoids ≥10 mg12120.9Comorbidities49410.004ConclusionThe impact of COVID 19 in Argentina, in terms of mortality in patients with IMADs was still higher compared to the general population during the second wave. However, the frequency of hospitalizations and ICU admissions was lower. These findings could be explained by the introduction of the SARS COV 2 vaccination and, probably, by the cumulative knowledge and management improvement of this infection among physicians.References[1]Isnardi CA et al. Epidemiology and outcomes of patients with rheumatic diseases and SARS-COV-2 infection: data from the argentinean SAR-COVID Registry. Ann Rheum Dis, 2021, suppl 1, 887.Disclosure of InterestsNone declared

Background30% of patients with SLE have APS, so clinical thromboembolic, obstetric and laboratory manifestations have been extensively studied in this population. The association between antiphospholipid antibodies (aPL) and non-thrombotic manifestations that are not part of the Sydney classification criteria for APS are particularly important in patients with SLE.ObjectivesTo compare the presence of non-criteria non-thrombotic manifestations of APS in patients with SLE and APS, SLE with positive aPL, SLE with negative antibodies and different outcomes such as mortality, hospitalizations and damage score.MethodsObservational, analytical and cross-sectional multicenter study. Data were obtained from the review of the RELESSAR database. We included patients ≥ 18 years with diagnosis of SLE according to modified ACR 1984 criteria. The diagnosis of APS was made according to the Sidney Criteria 2006. The sample was classified into three groups based on the presence of established APS (Group 1), aPL carrier (Group 2) and aPL negative (Group 3). Non-criteria manifestations were described and compared in the three groups. Continuous variables were compared by Student’s or Mann Whitney’s T test, and categorical variables by Chi[2]test or Fisher’s exact test. In cases where a significant difference was found between the groups, multiple post hoc comparisons were made.ResultsOne thousand two hundred and two patients were included, 1,110 (92.3%) were women. One hundred and sixty patients (13.3%) had APS (group 1), 241 (20.04%) were aPL carrier (group 2) and 801 (66.6%) were negative for aPL (group 3). Patients with APS were older than patients in group 2 [42.6 (SD 13.5) vs 38 (SD 14.2), p 0.001] and 3 [42.6 (SD 13.5) vs 39.5 (SD 14.1) p 0.004]. The disease duration was longer in patients with APS compared to patients with SLE and negative aPL (138 months (SD 113) vs 101 (SD 113) (p <0.001). Table 1 shows non-thrombotic manifestations in the three groups. A higher percentage of patients with hemolytic anemia was observed in the APS group (p=0.001) and in the aPL carrier group (p=0.018) compared to negative aPL group. Patients with APS showed a higher proportion of thrombocytopenia when compared to patients with negative aPL (p=0.039). Acute cranial/peripheral neuropathy was more frequently observed in APS group compared to aPL-negative group (p=0.006). APS group was significantly associated with hospitalizations due SLE flares, morbidity and damage index (Table 2). A higher proportion of patients in the APS group had thrombotic events compared to aPL carrier and aPL negative groups (p<0.05).Table 1.Non-criteria non-thrombotic manifestationsAPS (group 1)aPL + (group 2)aPL – (group 3)pHemolytic anemia31 (19.9%)37 (15.4%)75 (9.47%)<0.001Thrombocytopenia41 (26.6%)56 (23.4%)138 (17.6%)0.011Depression23 (14.8%)17 (7.05%)92 (11.6%)0.041Acute Neuropathy10 (6.62%)9 (3.73%)14 (1.77%)0.002Table 2.Patient prognostic measuresAPS (group 1)aPL + (group 2)aPL – (group 3)pHospitalizations96 (62.3%)119 (49.8%)401 (50.4%)0.02Charlson Score2.43 (1.92)2.01 (1.51)1.95 (1.46)0.009SLICC1.53 (1.66)1.04 (1.32)0.960 (1.34)<0.001ConclusionIn this nation-wide SLE cohort, neurological and hematological manifestations were frequently observed in patients with secondary APS. Moreover, these patients had higher rate of hospitalization, damage score and comorbidities.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundLupus nephritis (LN) is one of the most frequent serious Lupus manifestations and it is an important risk factor for overall morbidity and mortality in patients with SLE. Despite potent anti-inflammatory and immunosuppressive therapies, it persists with a significant number of patients who progress to chronic renal failure.ObjectivesTo evaluate the prevalence of LN and the characteristics of patients with this complication in search of a potential higher risk profile for the development of kidney disease.MethodsIt was a retrospective, observational and analytical study, based on the database of the national registry of SLE of the Argentine Society of Rheumatology (RELESSAR). Adult patients who met the ACR 1997 Classification Criteria were included. Sociodemographic data, time of disease evolution, and delay in diagnosis were collected. The antibody profile, activity indices (SLEDAI), comorbidities (Charlson), treatments and damage (SDI) were determined. Patients with current or past LN were compared with those without LN.Results1502 patients were analyzed, of which 643 (42.8%) had LN. The predominant histological classes were class IV in 253 cases, class III in 81, class II in 78, and class V in 33 patients.In the univariate analysis, patients with LN were characterized by belonging more frequently to the mestizo ethnic group (p=0.017), having a younger age at entry into the registry (p<0.001), less delay in diagnosis in months (p<0.001) and longer disease duration (<0.001). They also presented higher SLEDAI in the last evaluation (p<0.001) as well as low complement levels (p<0.001) and a higher frequency of positive anti-SM antibodies (p<0.007).Within the comorbidities they had significantly more dyslipidemia (p<0.001) and arterial hypertension (p <0.001). They had more episodes of hospitalization (p<0.001), more serious infections (p<0.001) and a higher SLICC damage index (p=0.001).The treatments received any time were Azathioprine (44.3% vs 27.9%, p<0.001), Cyclophosphamide (66.2% vs. 8.72%, p<0.001), mycophenolate mofetil (47.0% vs 7.37%, p< 0.001), mycophenolic Acid (5.59% vs. 0.39%, p<0.001) and Belimumab (3.7% vs. 8.03%, p<0.001).The multivariate analysis is described in Table 1.ConclusionIn the RELESSAR registry, the prevalence of LN was 42.8%. These patients were characterized by being more frequently of mestizo origin, younger at last evaluation, and of lower socioeconomic level. There was also a correlation with the global activity of the disease as well as with low complement levels and anti-SM antibodies positive. Within the comorbidities there was a strong association with arterial hypertension. We also highlight the negative association with acute cutaneous lupus and with the presence of antiphospholipid antibodies.Table 1.- Result of the multivariate model.CharacteristicsORCIpAge at last visit0.960.94-0.97<0.001SLE duration1.011.00-1.01<0.001SES Media/low/very low1.651.02-2.710.044SLEDAI1.091.06-1.13<0.001Acute Cutaneous Lupus0.570.42-0.78<0.001Positive Anti SM antibodies1.431.06-1.92= 0.019Low Complement (> than 10 days or persist during the last 10 days4.522.78-7.65<0.001Negative Anti phospholipid antibodies1.741.27-2.39<0.001Arterial Hypertension3.002.10-4.31<0.001Gastroduodenal ulcer0.360.17-0.730.006REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundThe goal of targeted treatment in patients with Systemic Lupus Erythematosus (SLE) is to achieve clinical remission or low disease activity, with the best quality of life, low damage rates and better survival 1-4. RELESSAR is a multicenter, cross-sectional study registry of ≥18 years SLE (ACR 97) patients 5.ObjectivesTo describe demographic, clinical characteristics and treatments in SLE patients according to disease activity state. To evaluate the proportion of SLE and refractory SLE patients that are potentially candidates for Belimumab treatment (Active SLE despite standard treatment including increased acDNA autoantibodies and low complement).MethodsWe evaluated demographic and clinical data, treatments, score of damage (SLICC), activity (SLEDAI) and comorbidity (Charlson), hospital admissions and severe infections. The patients were compared according to disease activity: remission (SLEDAI = 0 and without corticosteroids), low disease activity (LDA, SLEDAI> 0 and ≤4 and without corticosteroids) and non-optimal control (SLEDAI> 4 and any dose of corticosteroids). Refractory SLE was defined according to Rituximab (RTX) use, non-response to cyclophosphamide or two or more immunosuppressant or splenectomized patients. Potential use of Belimumab according approved prescription in Argentina was analyzed.ResultsOverall, 1277 patients were analyzed: 299 (23.4%) were in remission, 162 (12.7%) in LDA and 816 (63.9%) with non-optimal control of the disease.Patients in non-optimal control group were younger, less frequently female and they showed less time of disease and lower socioeconomic status (p < 0.001). They were also more prevalent mestizos (p= 0.004), had higher SLEDAI and SLICC indexes (p <0.001) and higher use of immunosuppressant therapy (p <0.001). There was no difference regarding biologic treatment (RTX p= 0.547 and Belimumab p= 0.08). This group had higher proportion of hospital admissions and severe infections (p<0.001, respectively).Two hundred and one SLE patients fulfilled the use of Belimumab prescription criteria but only 45/201 patients (22,3%) received it in the last visit. Malar rash was the only clinical variable associated with the use of Belimumab (72.7% vs 29.8% p= 0.005).Seventy-six patients classified as refractory SLE (15.7%) and 56/76 (75.7%) never received Belimumab. Patients on Belimumab therapy were associated to treatment with lower doses of corticoids (p= 0.018) and lower rate of hospital admission caused by SLE flare (p= 0.027).ConclusionA high percentage of patients had uncontrolled disease upon entry into the registry and were potential candidates for treatment with Belimumab. The patients who received biologic treatment showed the benefit of requiring fewer doses of corticosteroids and having a lower rate of hospitalizations.References[1]Mok CC. Treat-to-target in systemic lupus erythematosus: Are we there yet? Expert Rev Clin Pharmacol. 2016;9(5).[2]Morand EF, Mosca M. Treat to target, remission and low disease activity in SLE. Vol. 31, Best Practice and Research: Clinical Rheumatology. 2017.[3]Golder V, Tsang-A-Sjoe MWP. Treatment targets in SLE: Remission and low disease activity state. Rheumatol (United Kingdom). 2020;59.[4]Ruiz-Irastorza G, Bertsias G. Treating systemic lupus erythematosus in the 21st century: new drugs and new perspectives on old drugs. Vol. 59, Rheumatology (United Kingdom). 2021.[5]Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum [Internet]. 1997;40(9):1725. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9324032Disclosure of InterestsRosana Quintana: None declared, Lucila Garcia: None declared, Paula Alba: None declared, Susana Roverano: None declared, Analia Alvarez: None declared, Cesar Graf: None declared, Cecilia Pisoni: None declared, Alberto Spindler: None declared, Catalina Gomez: None declared, Heber Matias Figueredo: None declared, Silvia Papasidero: None declared, Raul Horacio Paniego: None declared, Maria DeLaVega: None declared, Emma Estela Civit De Garignani: None declared, Luciana Gonzalez Lucero: None declared, Victoria Martire: None declared, Rodrigo Águila Maldonado: None declared, Sergio Gordon: None declared, Carla Gobbi: None declared, Romina Nieto: None declared, Gretel Rausch: None declared, Vanina Góngora: None declared, Maria Agustina D´Amico: None declared, Diana Dubinsky: None declared, Alberto Omar Orden: None declared, Johana Zacariaz: None declared, Julia Romero: None declared, Mariana Alejandra Pera: None declared, Oscar Rillo: None declared, Roberto Baez: None declared, Valeria Arturi: None declared, Andrea Gonzalez: None declared, Florencia Vivero: None declared, Marcela Schmid: None declared, Victor Caputo: None declared, Maria Silvia Larroude: None declared, Graciela Gomez: None declared, Graciela Rodriguez: None declared, Josefina Marin: None declared, Maria Victoria Collado: None declared, Marisa Jorfen: None declared, Zaida Bedran: None declared, Judith Sarano: None declared, David Zelaya: None declared, MONICA SACNUN: None declared, Pablo Finucci: None declared, Romina Rojas Tessel: None declared, Maria Emilia Sattler: None declared, MAXIMILIANO MACHADO ESCOBAR: None declared, Pablo Astesana: None declared, Ursula Vanesa Paris: None declared, Alberto Allievi: None declared, Juan Manuel Vandale: None declared, Bernardo Pons-Estel: None declared, Guillermo Pons-Estel: None declared, Mercedes García Grant/research support from: GSK grant