Background Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the endothelium of medium- and large-sized blood vessels [1]. Even though the pathogenic mechanisms that drive GCA are yet to be settled, there is strong evidence that CD4+ T lymphocytes play a crucial role in the development of this vasculitis [2]. Recently, single-cell RNA sequencing has resulted in a scientific and technological revolution, enabling the characterization of the gene expression profile of thousands of individual cells in different tissues [3]. This approach has allowed the identification of new cell subtypes, some of them being exclusively represented in pathogenesis, and has also proved useful as a tool for reporting new disease-specific biomarkers. Objectives In this study, we aimed to define new pathological mechanisms driving GCA through the comprehensive characterization of the gene expression profile of CD4+ T cells by performing single-cell RNA sequencing in GCA patients and healthy controls. Methods CD4+ T cells from whole blood of 16 individuals (eight GCA patients and eight sex- and age-matched healthy controls) were obtained. Based on clinical parameters, five patients were classified as active GCA and 3 of them as patients in remission. Single-cell libraries were prepared from isolated CD4+ T cells using the ‘Chromium Single Cell Gene Expression‘ (10X Genomics). Sequencing data were pre-processed with the CellRangerV3.0 software. Then, quality control analysis, dimensionality reduction, clustering and differential gene expression profiling were conducted with the R package Seurat V4[4]. Results A total of 114.799 cells were analyzed and classified into 13 clusters according to their transcriptomic profile. Manual annotation of the different clusters based on canonical markers permitted the identification of 6 distinct CD4+ T cell types including naïve (Tnaïve), central memory (TCM), effector memory (TEM), effector memory expressing granzyme K (TEM GZMK+), regulatory (Tregs) and cytotoxic T lymphocytes (CTL). The comparative analysis of cell type composition between the different subgroups showed a significant reduction of the cytotoxic cell compartment in GCA patients in remission compared with active patients (p=0.011) and controls (p=0.045) as well as a decreased frequency of Tregs in active patients compared with healthy individuals (p=0.029). In addition, differential expression analysis evidenced a significant overexpression of granzyme B (GZMB) and the zinc finger protein 683 (HOBIT), both involved in cytotoxic processes, in CTLs of active patients compared with patients in remission (p=0.017) and controls (p=1.14x10-49), respectively. Moreover, in both active and in remission patients, the Treg compartment showed a reduced expression of genes related to regulatory functions, like HLA-DRA (p=3.34x10-7) and LGALS1 (p=1.14x10-8), compared with healthy controls. Conclusion The first single-cell atlas of CD4+ T cells in GCA provided evidence for the first time of a potential pathogenic role of CD4+ T cells with cytotoxic functions in this vasculitis and supported the crucial role of Tregs in the pathogenesis of GCA. References [1]Jennette JC et al. 2012 Revised International Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013.[2]Robinette ML. The Immunopathology of Giant Cell Arteritis Across Disease Spectra. Front Immunol 2021.[3]Cheung P et al. Single-cell technologies — studying rheumatic diseases one cell at a time. Nat Rev Rheumatol 2019.[4]Hao Y et al. Integrated analysis of multimodal single-cell data. Cell 2021. Acknowledgements: NIL. Disclosure of Interests None Declared.Figure 1T CD4+ cell overview in GCA. (A) UMAP of CD4+ T cells distributed by expression. (B) Barplot of each T cell sub-type contribution. (C) Dotplot of CTL and Treg clusters for specific genetic markers classified per group. Dot size indicates proportion of cells expressing the gene, color indicates average of expression.

Background In Spondyloarthritis (SpA) a higher prevalence of cardiovascular comorbidities has been observed, such as diabetes mellitus (DM), arterial hypertension (AHT), dyslipidaemia (DLP), obesity and metabolic syndrome [1]. In recent years, several studies have established a causal relationship between non-HDL cholesterol (non-HDLC) levels and cardiovascular diseases. Non-HDLC offers a wide vision of proatherogenic lipoproteins containing apolipoprotein B (apoB) -VLDL, IDL, LDL, chylomicron remnants and Lp(a)- without being interfered by triglyceride concentrations. Thus, non-HDLC has become an innovative cardiovascular risk (CVR) biomarker. Therefore, the Multinational Cardiovascular Risk Consortium [2] recently published a set of recommendations estimating CVR based on non-HDLC levels. We have analyzed in a cohort of patients with SpA possible associations between clinic and laboratory data, and non-HDLC serum levels. Objectives To analyse in patients with SpA whether there is a relationship between disease-dependent variables (C-reactive protein [CRP] levels, erythrocyte sedimentation rate [ESR], presence of HLA-B27, axial or peripheral involvement, structural damage, and extra-articular manifestations) with non-HDLC serum levels. Methods Observational, cross-sectional, single-centre study, which included a sample of 104 patients with both radiographic and non-radiographic SpA, in whom each disease-dependent variable was analyzed individually for its possible association with non-HDLC serum levels. Classical CVR factors were also analyzed. Results Of 104 patients included most of them were women (54,8%), mean age was 43 years, 33,7% smoked, HLA-B27 was positive in 52,9% of patients, with mean CRP levels of 9,83 mg/L and ESR of 17,92 mm/h. Axial involvement prevailed over peripheral (92,3% vs 26%). Extra-articular manifestations were distributed as follows: 13,5% uveitis, 7,7% inflammatory bowel disease (IBD) and 4,8% psoriasis. 43,3% of patients had structural damage. None of these patients suffered from cardiovascular disease prior to diagnosis. Regarding the classic CVR factors: AHT was observed in 16,3%, DM in 1.92%, obesity (BMI >30) in 14.4%. Mean non-HDLC was 144.19 mg/dL (± 36,1), giving this population a 12,87% probability of suffering cardiovascular disease at the age of 75. For CVR estimation, we categorized non-HDLC levels according to low (100 - <145 mg/dL), moderate (145 - <185 mg/dL), high (185 - <220) and very high (≥220 mg/dL) levels. Lower mean concentrations of non-HDLC were found in those patients with IBD (117,6 ± 35,7 mg/dL), compared to those without intestinal involvement (146 ± 35,5 mg/dL) (p<0,05). No statistically significant relationships were observed between non-HDLC and the rest of disease-dependent variables. Conclusion In our cohort of patients, mean levels of non-HDLC were elevated (144 mg/dL), giving patients a 13% probability of suffering cardiovascular disease at the age of 75. Of clinical and laboratory features analyzed, we observed lower serum concentration of non-HDLC in patients with IBD. This could be explained by lipid malabsorption, as inflammatory damage of the intestinal epithelium decreases the synthesis of apo-B48, which is necessary for both chylomicron formation and hepatic synthesis of apo-B100 [3]. This may turn into lower serum levels of non-HDLC. Therefore, presence of IBD in patients with SpA should be kept in mind when defining non-HDLC levels as an estimator of CVR. References [1]Castaneda S, Nurmohamed MT, Gonzlez-Gay MA. Cardiovascular disease in inflammatory rheumatic disease. Best Pract Res Clin Rheumatol. 2016;30: 851-69. [2]Brunner FJ, et al. Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium. Lancet. 2019;394(10215):2173–83. [3]Edge SB, Hoeg JM, Schneider PD, Brewer HB Jr. Apolipoprotein B synthesis in humans: liver synthesizes only apolipoprotein B-100. Metabolism. 1985;34(8):726–30. Acknowledgements: NIL. Disclosure of Interests None Declared.

BackgroundOcular and Neurobehçet’s Disease (NBD) are the most severe manifestations of Behcet’s disease (1-4). NBD can be classified as a) primary neural parenchymal lesions, also known as parenchymal NBD (p-NBD) or b) secondary to vascular involvement or non-parenchymal NBD (np-NBD) (4). Response to biologic therapy (BT) in these two refractory subtypes of NBD is unknown.ObjectivesTo assess efficacy and safety of BT in refractory subtypes of NBD.MethodsOpen-label multicenter study of refractory NBD from 21 different referral National Hospitals. NBD diagnosis was based on the International Consensus Recommendation criteria (4). Efficacy was determined by complete or partial response and no-response. Complete, partial or no response was defined according to the resolution of the neurological syndrome (signs and/or symptoms) after the BT onset.ResultsWe studied 41 patients (21 women/20 men; mean age: 40.6±10.8 years). NBD was classified as p-NBD (n= 33, 80.5%) and np-NBD (n=17, 41.5%). There were no significant differences in baseline general features and in neurological clinical response in both subgroups (Table 1 and Figure 1). The first BT used in p-NBD were Infliximab (IFX) (n=15), Adalimumab (ADA) (n=11), Golimumab (GLM) (n=3), Tocilizumab (TCZ) (n=2) and Etanercept (ETN) (n=2) and in np-NBD were IFX (n=9), ADA (n=6), TCZ (n=1) and ETN (n=1).Table 1.Main features of p-NBD and np-NBDTotalp-NBDnp-NBDP p-NBD vs np-NBDAge at biological therapy initiation, years (mean±SD)44±13.941.4±9.639.4±10.60.412Gender, n (m/f) (%)21/20 (48.8/52.2)18/15 (54.5/45.5)5/12 (29.4/70.6)0.091HLAB51 +/ patients tested, n (%)15/31 (57.7)14/25 (58.3)4/10 (40)0.391Oral aphthae, n (%)40 (97.6)32 (97)15 (88.2)0.323Cutaneous involvement, n (%)28 (63.4)23 (69.7)10 (58.8)0.603Ocular involvement, n (%)21 (48.8)15 (45.5)9 (52.9)0.616Vascular involvement, n (%)9 (22)10 (30.3)7 (41.2)0.442Articular involvement, n (%)9 (22)7 (21.2)3 (17.6)0.765Previous conventional Immunosuppressive drugs to BTAzathioprine24 (58.5)20 (60.6)10 (58.8)-Methotrexate16 (39.0)12 (36.4)3 (17.6)-Cyclophosphamide13 (31.7)13 (39.4)5 (29.4)-Cyclosporine A9 (22.0)8 (24.2)3 (17.6)-Mycophenolate Mofetil2 (4.9)2 (6.1)0-Figure 1.Response to biological therapy according to NBD subtypes.After an overall mean follow-up of 57.5±50.9 months BT was switched in 22 patients due to inefficacy (n=16) or Adverse Effects (AE) (n=6) and in 4 cases was definitively discontinued because of complete prolonged remission (n=3) or AE (n=1). AE were observed in 7 (17.1%) patients. Severe AE were observed in 2 cases, one due to demyelinating disease and the other due to pulmonary tuberculosis, both in patients undergoing IFX therapy. The other 6 AE were infusion reaction to IFX (n=1), IFX-induced psoriasis (n=1), IFX-induced acneiform eruption (n=1), infusion reaction to TCZ (n=1), intolerance to IFX and recurrent mild infections (n=1) and erosive lichen planus and bullous impetigo (n=1).ConclusionIn our series, BT seems equally effective and safe in both refractory p-NBD and np-NBD.References[1]Martín-Varillas JL, et al. Ophthalmology 2018 Sep;125(9):1444-1451. doi: 10.1016/j.ophtha.2018.02.020.[2]Atienza-Mateo B, et al. Arthritis Rheumatol 2019 Dec;71(12):2081-2089. doi: 10.1002/art.41026.[3]Santos-Gómez M, et al. Clin Exp Rheumatol 2016 Sep-Oct;34(6 Suppl 102): S34-S40.[4]Kalra S, et al. Diagnosis and management of Neuro-Behçet’s disease: international consensus recommendations. J Neurol. 2014 Sep;261(9):1662–76.Disclosure of InterestsAlba Herrero-Morant: None declared, José Luis Martín-Varillas Grant/research support from: AbbVie, Pfizer, Lilly, Janssen, UCB, and Celgene, Santos Castañeda Paid instructor for: Assistant professor of the Cátedra UAM-ROCHE, EPID-Future, UAM, Madrid, Spain, Olga Maiz-Alonso: None declared, Julio Sanchez-Martin: None declared, Norberto Ortego: None declared, Enrique Raya: None declared, Águeda Prior-Español: None declared, Clara Moriano: None declared, Rafael Melero: None declared, Jenaro Graña: None declared, ANA URRUTICOECHEA-ARANA: None declared, Angel Ramos Calvo: None declared, Marta Loredo Martínez: None declared, Eva Salgado-Pérez: None declared, Francisca Sivera: None declared, Ignacio Torre-Salaberri: None declared, J. Narváez Speakers bureau: Bristol-Myers Squibb, José Luis Andréu Sánchez: None declared, Olga Martínez González: None declared, Ricardo Gómez de la Torre: None declared, Sabela Fernández: None declared, Susana Romero-Yuste: None declared, Iñigo Gonzalez-Mazon: None declared, Carmen Álvarez-Reguera: None declared, David Martínez-López: None declared, J. Luis Hernández: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche

Background The survival of patients with systemic lupus erythematosus (SLE) has increased in recent years, but they have higher morbidity and mortality than the general population. Purpose To study the prevalence of comorbidities in patients with SLE and its relationship with damage, gender and treatments received. Methods Cross-sectional multicenter descriptive study of a cohort of adult patients with SLE. Results We studied 3,656 patients, 90.3% women, mean age (±SD) at diagnosis of 35.2(±14.7) years and duration of SLE of 142.6(±100.8) months. We analyzed 27 comorbidities. 79.73% of the patients presented any, with the maximum accumulated being 14. The most frequent were smoking, dyslipidemia and arterial hypertension. 38.05% of patients accumulated damage. Males accumulated more comorbidities (85.48% vs. 79.1%, p=0.003) and damage (47.03% vs. 37.11%, p<0.001). The first criterion for SLE appeared at a younger age in patients who did not have comorbidities: 27.73(±12.04) years vs. 34.47(±14.76) years; p<0.001. We found that there is a positive correlation between the number of comorbidities and the number of systems with damage (Spearman's Rho = 0.478, p<0.001). There is a positive correlation between the number of comorbidities and damaged systems with the number of hospitalizations by disease activity (Rho=0.265 and 0.396 respectively, p<0.001 in both contrasts) as well as with the number of serious infections (Rho=0.299 and 0.307 respectively, p <0.001 in both contrasts). We found more patients without comorbidities in those who did not receive glucocorticoids (9.94% vs. 15.48%, p<0.001) and more patients with comorbidities in those who did not receive antimalarials (89.1% vs. 81.78%, p<0.001). There were significant differences in the presence of comorbidities in those treated with cyclophosphamide, mycophenolate, azathioprine or rituximab. Conclusions A high percentage of patients with SLE have comorbidities. With few exceptions, they are more frequent in males. The onset of SLE was later in patients with more comorbidities. We found variations in comorbidities depending on the treatments received.

BackgroundSystemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSC), Sjögren’s syndrome (SJS), mixed connective tissue disease (MCTD), primary antiphospholipid syndrome (PAPS) and undifferentiated connective tissue disease (UCTD) are classified as systemic autoimmune diseases (SADs). They are diagnosed based on different clinical and laboratory criteria. Due to their high internal heterogeneity and overlapping symptoms, SADs are difficult to diagnose. Therefore, molecular and cellular-based studies need to be undertaken to precisely classify the patients. Mass cytometry is a single-cell proteomics technology that measures approximately 50 markers per cell, thus it is a suitable tool to perform deep-phenotyping studies in SADs.ObjectivesExplore differences and similarities between SADs and build reclassification framework using high-dimensional cytometry data.MethodsThe whole blood samples collected from 129 individuals, including patients and controls were stained with a 39-plex antibody panel and acquired in 9 batches on a CyTOF (HELIOS) instrument. Data were cleaned, and normalized for batch effects using semi-automated cytof analysis pipeline. Cell frequencies and median signal intensities (MSI) for each population were extracted using FlowSOM for mononuclear cells (PBMC) and Phenograph for granulocytes. Secretion of 44 cytokines and chemokines were analyzed using a multiplexed luminex assay. Diseases were compared by Kruskal-Wallis analysis and hierarchical clustering and reclassification was done using unsupervised k-means clustering. Cytokine analysis across clusters was performed using Kruskal-Wallis test.ResultsDifferently expressed features were observed between patient groups, regarding frequency of classical monocytes, B and T cells subpopulations, mature and immature granulocytes and intensities of CD38, HLA-DR and CD95 across various populations. However, none of them were disease specific. K-means clustering identified four patient clusters, which were composed by a mixture of different diagnosis. Cluster C1 was characterized by increased levels of circulating cells from PBMC compartment, and lower activation of different populations of the T cell compartment. It presented lower frequency in multiple granulocyte populations and the highest expression of CD95 and CD38. This cluster was also associated with antimalarial and steroid treatment. Clusters C1 and C2 were exactly opposite to each other, cluster C3 was characterized by intermediate features between C1 and C2 and cluster C4 could be considered as undifferentiated, mixed group. Higher production of TNFα, IL-10 and IP-10 were found in patients from C1 compared to C2, suggesting more active phenotype in C1 and physiological one in C2. The cytokine levels were independent of the treatment.ConclusionWe constructed a patient reclassification framework using cell frequencies and expression levels of functional markers. To our knowledge this is the first time when 7 different SADs were compared using mass cytometry. In agreement with other reports we did not detect any disease-specific cellular markers. Distribution of diagnosis across different clusters confirms diseases heterogeneity. Patients can be classified into phenotypically similar groups, that could potentially benefit from the same line of treatment.AcknowledgementsThis project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 831434 (3TR) and The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. Also from No 115565 PRECISESADS.Disclosure of InterestsNone declared

Background Systemic lupus erythematosus (SLE) is regarded as a prototype autoimmune disease because it can serve as a means for studying differences between ethnic minorities and sex. Traditionally, all Hispanics have been bracketed within the same ethnic group, but there are differences between Hispanics from Spain and those from Latin America, not to mention other Spanish-speaking populations. Objectives This study aimed to determine the demographic and clinical characteristics, severity, activity, damage, mortality and co-morbidity of SLE in Hispanics belonging to the two ethnic groups resident in Spain, and to identify any differences. Methods This was an observational, multi-centre, retrospective study. The demographic and clinical variables of patients with SLE from 45 rheumatology units were collected. The study was conducted in accordance with Good Clinical Practice guidelines. Hispanic patients from the registry were divided into two groups: Spaniards or European Caucasians (EC) and Latin American mestizos (LAM). Comparative univariate and multivariate statistical analyses were carried out. Results A total of 3490 SLE patients were included, 90% of whom were female; 3305 (92%) EC and 185 (5%) LAM. LAM patients experienced their first lupus symptoms four years earlier than EC patients and were diagnosed and included in the registry younger, and their SLE was of a shorter duration. The time in months from the first SLE symptoms to diagnosis was longer in EC patients, as were the follow-up periods. LAM patients exhibited higher prevalence rates of myositis, haemolytic anaemia and nephritis, but there were no differences in histological type or serositis. Anti-Sm, anti-Ro and anti-RNP antibodies were more frequently found in LAM patients. LAM patients also had higher levels of disease activity, severity and hospital admissions. However, there were no differences in damage index, mortality or co-morbidity index. In the multivariate analysis, after adjusting for confounders, in several models the odds ratio (95% confidence interval) for a Katz severity index >3 in LAM patients was 1.45 (1.038-2.026; p = 0.02). This difference did not extend to activity levels (i.e. SLEDAI >3; 0.98 (0.30-1.66)). Conclusion SLE in Hispanic EC patients showed clinical differences compared to Hispanic LAM patients. The latter more frequently suffered nephritis and higher severity indices. This study shows that where lupus is concerned, not all Hispanics are equal.

Background:Tocilizumab (TCZ) is the only biological agent approved in Giant Cell Arteritis (GCA). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is scarce.Objectives:Our aim was to assess efficacy and safety of TCZ therapy optimization in an unselected wide series of GCA in clinical practice.Methods:Multicenter study, 134 patients with GCA who received TCZ due to inefficacy/adverse events of previous therapy. Once complete remission was reached and based on a shared decision between patient and physician TCZ was optimized in some cases. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively.Results:134 GCA patients treated with TCZ (101w/33m); mean age 73.0±8.8 years. TCZ was administered IV to 106 (79.1%) patients and SC to 28 (20.9%). TCZ was optimized in 43 (32.1%) patients. No demographic, clinical manifestations or laboratory data differences had been found at TCZ onset (TABLE). After a follow up of 12 [6-15.5] months, and a complete remission for 6 [3-12] months; the first TCZ optimization was performed. Median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. TCZ IV was optimized from 8 to 4 mg/kg/4weeks in 12 of 106 (11.3%) and from 162 mg/SC/week to 162 mg/SC/2weeks in 9 of 28 (32.1%) cases. Five (11.6%) of the 43 optimized cases relapsed. In 4 cases, the relapses were treated increasing TCZ up to the pre-optimization dose, in 1 case the route of administration was change (4 mg/kg/4week to 162 mg/SC/week). In 8 of 43 optimized patients (18.6%), it was possible to withdraw TCZ after complete remission for 30 [16.25-45.75] months. Regarding adverse events and severe infections were similar in both groups. The mean TCZ treatment costs were lower in the optimized group.Conclusion:Once remission is reached in GCA patients under TCZ treatment, optimization of TCZ may be performed. Based on our experience it could be performed by reducing the dose with IV TCZ or by prolonging dosing interval with SC TCZ.References:[1]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLE.OPTIMIZED-TCZ GROUP (n=43)NON-OPTIMIZED TCZ GROUP (n=91)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURESAge, years, mean± SD68.9±8.771.4±8.50.125Sex, female/male n(%)32/1068/240.779Time from GCA diagnosis to TCZ onset (months), median [IQR]19.5[7.75-45]10.5[4 – 25]0.047SYSTEMIC MANIFESTATIONSFever, n(%)1(2.4)8(8.7)0.176Constitutional syndrome, n(%)11(26.2)19(20.7)0.476PMR, n(%)18(42.9)56(60.9)0.052ISCHEMIC MANIFESTATIONSVisual involvement, n(%)5(11.9)23(25)0.084Headache, n(%)26(61.9)42(45.7)0.081Jaw claudication, n(%)1(2.4)11(12)0.072CORTICOSTEROIDS AT TCZ ONSETPrednisone dose, mg/d mean (SD)15.1±11.125±17.40.001FOLLOW-UP ON TCZ THERAPY (MONTHS), MEDIAN [IQR]24[18-27]6 [3-18]0.000Relapses, n(%)5(11.6)5(5.5)0.207End follow-up remission, n(%)40(93)84(92)0.99Severe side efects, n(%)14(32.6)22(24.2)0.307Seriuos infections, n(%)6(14)10(11)0.878Cost, (mean) euros per yearIVSC7 538.47 329.011 726.411 726.4--Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background: Psoriatic arthritis (PsA) is an inflammatory disorder of unknown etiology. Several domains are affected as peripheral or axial joints, enthesitis, dactylitis, nails as well as skin. Diverse cytokines have been described in the pathology of PsA as TNFα, IL-17 and IL-23. Ustekinumab (UST) is a fully human IgG1κ monoclonal antibody to interleukin 12/23. Its efficacy and safety have been tested in several clinical trials and registries. Nevertheless data from real word evidence studies is needed to understand the effectiveness, safety and behavior of UST in a different population of patients from randomized controlled trials Objectives: Analyze the persistence of UST 45 and 90 mg along 52 weeks of treatment Methods: Drug survival, effectiveness and security of UST were studied in a population of 64 PsA patients treated in the period between August 2014 to October 2019. Drug survival was defined as the time from initiation to discontinuation (stop/switch) of bDMARDs. For the determination of drug survival, Kaplan-Meier survival curves and Cox-regression analyses were used. Effectiveness was described as a reduction in the use of corticosteroids and in the levels of CRP along the study. All adverse events were recorded during the study Results: 64 patients were included with a mean follow-up of 57,2 weeks. At baseline the mean age was 47,8 years (8,9). 54,7% of patients were women and 45,3% were male. 31,3% were obese. Mean disease duration was 7,9 (5,0) years. 45,3% presented peripheric arthritis; 32,8% axial involvement; 31,3% enthesitis; 80% psoriasis. Patients were 45% bDMARDs-naïve; had a previous bDMARDs in 20,3% and ≥ than two bDMARDs in 34,4%. 30% of the patients had co-therapy with methotrexate and 29,7% of patients received corticosteroid therapy. Mean CRP was 7,9 (12,7) mg/L. The global probability of survival for UST was 96%, 83,9% and 60% at week 12, 24 and 52 respectively. High UST dosage was associated with favorable drug survival (at 52W: UST 45 mg=40,1%; UST 90 mg=75,8%; UST 45 to 90 mg*=88,9%) (p=0,008). The bDMARDS-naïve population also correlated with favorable UST survival (at 52W: bDMARDS-naïve=66,1% vs bDMARDS-experienced=56,7%), however no statistical significance was found (p=0,196). No difference in survival was observed among patients with or without axial involvement (W52: axial=58,2% vs non-axial=61,6; p=0,869). UST produced a reduction in the use of corticosteroids (30% vs 16%) and CRP levels (8,7 vs 7,7). Differences were greater in patients treated more than 28 weeks (maximum efficiency described for UST) (corticosteroids: 26% vs 16%; CRP levels: 8,5 vs 4,4). 4,9% of the patients suffered an AE. Most of them were non-serious AE: infections (3,3%) or headache (1,6%). The main cause of treatment discontinuation was lack of efficacy (30%), followed by primary failure (9,4%) and just a 3% due to AE Conclusion: The persistence of UST was dose-dependent and greater for the UST 90 mg dosage and for the population of bDMARD-naïve patients Drug survival of UST in the population of patients with axial involvement seems similar to the population of patients without axial affection which provide evidence of the efficacy of the IL23 inhibition in the axial domain of PsA UST decreased the use of corticosteroids and CRP levels along treatment The security profile of UST was to the drug. Only few non-serious AE reported during this study *UST 45 to 90 mg, patients who change from UST 45 to UST 90 mg dosage References: [1]Ritchlin C. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3. Ann Rheum Dis 2014;73:990–9 [2]McInnes IB. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 2013;382:780–9 Disclosure of Interests: None declared

Background: The mortality in Systemic Lupus Erythematosus (SLE) varies largely across different countries most probably due to social, healthcare and ethnic differences. Objectives: To analyze the causes and identify predictive factors of mortality of SLE in Spain in the present century. Methods: We performed a cross-sectional and retrospective study analyzing data from the RELESSER cohort (Spanish Registry of Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). We included all patients diagnosed with SLE since the year 2000 and recorded sociodemographic, clinical and serological variables, comorbidities and treatments, as well as indicators of disease activity, damage and severity. The characteristics of the deceased patients were compared with those of the survivors, and variables with clinical significance or statistical significance were grouped into multivariate models to determine which ones were independently associated with the outcome of the disease. Results: A total of 2004 patients were included, 88.6% female, the mean age at diagnosis was 38.3 (± 15.3) years, with a mean delay in diagnosis of 28.9 (± 52.6) months. Up to 2.84% of the individuals had died. The leading cause of death was SLE activity (n=16), followed by infections (n=14), vascular events (n=7) and cancer (n=6). The mean age of death was 54.68 (± 20.13) years, and neither age, sex nor delay in diagnosis was independently associated with mortality. The presence of nephritis, depression, severe infections, organ damage (SLICC/ACR DI) or disease activity (SLEDAI), as well as the use of cyclophosphamide, rituximab or high doses of corticosteroids, were predictors of mortality in our cohort. Antimalarial treatment and skin manifestations were linked to improved survival. Conclusion: In the RELESSER cohort, clinical factors, co-morbidities, as well as therapeutic attitudes were associated with a significant increase in mortality in SLE. Interestingly, depression was independently associated to mortality. The activity of the disease and infections continue to be the main causes of death at the beginning of the 21st century amongst our patients. Disclosure of Interests: Clara Moriano: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Inigo Rua-Figueroa: None declared, Elvira Diez Alvarez: None declared, Cristina Bermudez: None declared, Francisco J Lopez-Longo Grant/research support from: AbbVie and GSK, Speakers bureau: AbbVie, Actelion, Bristol Myers Squibb, GSK, MSD, Pfizer, Roche, and UCB Pharma, Maria Galindo-Izquierdo: None declared, Alejandro Olive: None declared, Eva Tomero Muriel: None declared, Antonio Fernandez-Nebro: None declared, Mercedes Freire Gonzalez: None declared, Olaia Fernandez- Berrizbeitia: None declared, Ana Perez Gomez: None declared, Esther Uriarte Isacelaya: None declared, Carlos Marras Fernandez Cid: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD, M. Rodiguez-Gomez: None declared, Paloma Vela-Casasempere: None declared, Alina Boteanu: None declared, J. Narvaez: None declared, Victor Martinez Taboada: None declared, Blanca Hernandez-Cruz Speakers bureau: Abbvie, Lilly, Sanofi, BMS, STADA, Jose Luis Andreu: None declared, Jose A Hernandez Beriain: None declared, Lorena Exposito: None declared, Raul Menor-Almagro: None declared, Monica Ibanez Barcelo: None declared, Ivan Castellvi Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Carles Galisteo: None declared, Enrique Raya: None declared, Victor Quevedo Vila: None declared, Tomas Vazquez Rodriguez: None declared, Jesus Ibanez: None declared, Jose M Pego-Reigosa: None declared

Objectives In patients with spondyloarthritis (SpA: axial SpA or psoriatic arthritis [PsA]), treated with golimumab as second biological therapy (after failure or withdrawal of a first anti TNF-α drug), we describe patients’ insights with regard to their beliefs and their satisfaction with golimumab therapy. Methods Patients on golimumab from GO-BEYOND, a retrospective study undergone in 20 Spanish rheumatology clinics, were requested to respond to the Beliefs About Medicines Questionnaire (BMQ). Statements of the BMQ include a 5-item necessity and a 5-item concern scale with Likert response options from “strongly agree” to “strongly disagree”. Patients also responded to questions on their satisfaction and experience with golimumab self-injection. Descriptive data are displayed, and responses to the BMQ in axial SpA vs PsA patients were compared with the chi-square test. Results 123 patients on golimumab as second anti TNF-α responded (81 axial SpA and 42 PsA, mean age 49 years [SD=11], 40% women). Patients showed strong beliefs in the necessity of golimumab for the treatment of their SpA (percentages of “agree” or “strongly agree” to the necessity statements: 50%–80%), but also concerns: half the patients agreed/strongly agreed to be worried about long term effects of golimumab, and ≈30% about becoming too dependent on the drug (table 1). Responses were similar in axial SpA and PsA patients (table 1). 111 patients declared to self-inject golimumab. Of these, 22.7% considered the experience with self-injection as very positive, 66.4% as positive, 10.0% neutral and only 0.9% unfavourable, and the use of the device very easy (37.3%), easy (57.3%), neutral (3.6%) and only 1.8% difficult. Finally 36.4% and 49.1% were very satisfied or satisfied with the interval of administration of golimumab, 11.8% were neutral and only 1.8% and 0.9% declared to be dissatisfied or very dissatisfied. Conclusions Patients with SpA currently using golimumab as second anti TNF-alpha describe strong beliefs in the necessity of golimumab and good experience and satisfaction with self-administration. The BMQ also identified concerns that should be addressed in the clinic. The study is limited to the subset of patients still on golimumab at the study visit. Acknowledgements Funded by Merck Sharp and Dohme, Spain Disclosure of Interest None declared

Background Retinal vasculitis (RV) is a serious complication of uveitis due to Behçet’s disease (BD).1–2 Objectives We assess the short/long-term efficacy of Infliximab (IFX) in refractory RV of BD. Methods Multicenter study of patients with RV of BD refractory to corticosteroids and at least 1 conventional immunosuppressant (IS). We compared efficacy of IFX between baseline, 1st week, 1–6 months and 1–6 years. Results 72 patients/129 affected eyes (40♂/32♀) with mean age of 39.6±9.7 years. HLA-B51 was (+) in 63%. Before IFX onset, patients had received: oral/e.v. glucocorticoids (n=98), CyA (n=56), AZA (n=43), MTX (n=34) and other IS (n=22). IFX was used as monotherapy in 17 patients and combined with conventional IS in the remaining 55. IFX dose was as follows: 3 mg/kg/4–8 w (n=5), 4 mg/kg/4 w (n=1), 5–5.5 mg/kg/4–8 w (n=66). Following IFX onset, an improvement in RV was seen, as well as in the other ocular outcomes. This enhancement was maintained (table 1). After a mean follow-up of 26.5±22.1 months, IFX was discontinued in 44: remission (n=15), primary failure (n=16), preference of another route of administration (n=8), pregnancy (n=1) and adverse effects (n=4). Conclusions IFX seems an effective short/long-term treatment in RV of BD. References [1] Calvo-Río V, Blanco R, Beltrán E, et al. Anti-TNF-alfa therapy in patients with refractory uveitis due to Behçet’s disease: a 1-year-follow-up study of 124 patients. Rheumatol. 2014; 53(12):2223–31 [2] Santos-Gómez M, Calvo-Río V, Blanco R, et al. The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behçet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol. 2016; 34 (6Suppl 102):S34-S40 Disclosure of Interest None declared