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BackgroundBaricitinib (BARI) is a selective and reversible oral Janus kinase (JAK) inhibitor for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients with inadequate response or intolerance to one or more antirheumatic drugs disease modifiers (DMARDs). Interstitial lung disease (ILD) is a common extra-joint manifestation of RA. Symptomatic ILD occurs in 5-17% of patients with RA and influences the natural course of the disease and substantially affects morbidity and mortality, which is why we wanted to review our patients with RA and ILD who are under treatment with BARI.ObjectivesTo assess the safety and persistence of BARI, as well as the evolution of lung function in patients with RA and ILD who are undergoing treatment with BARI, in the Rheumatology Service of the Donostia University Hospital.MethodsA retrospective search was carried out of all patients undergoing BARI treatment until June 2020. The electronic medical records were reviewed. The variables collected were: sex, age, date of diagnosis of RA, history of smoking, presence of erosions, positivity for rheumatoid factor (RF), citrullinated cyclic antipeptide (anti-CCP) and previous treatments. Regarding BARI, the dose, the time since the start of treatment, related adverse effects, reason for suspension and other relevant data were collected. The quantitative variables are shown with the median and interquartile range, the qualitative variables are shown with the absolute value and its percentage.Results17 patients with RA and ILD treated with BARI were found. Table 1 shows the clinical characteristics, Table 2 shows the treatments and Table 3 shows the respiratory function tests (RFT). All patients were positive for RF and anti-CCP, the presence of erosions was observed in 10 (59%), a history of smoking in 8 (47%), the most frequent type of ILD was Usual Interstitial Pneumopathy (UIP) 7 (41%), at the diagnosis of ILD Abatacept was the most used drug 14 (82). Before the start of BARI, the median FVC 90% (80.5-111), DLCO 69% (57-83.5) and the last control after the use of BARI the median FVC 94% (87-107), DLCO 63% (51-87), the median time of exposure to BARI was 34 months. To date, 10 (59%) patients continue with BARI and the most frequent cause of suspension was failure 2º.ConclusionA good persistence of BARI was observed (59%), it also proved to be a safe drug and kept lung function stable in these patients, so BARI can be a therapeutic option in these cases, although more studies are needed to better elucidate these findings.Figure 1.Disclosure of InterestsNone declared

BackgroundTreat to Target strategies are necessary in Systemic Lupus Erythematosus (SLE). They are difficult to establish due to the heterogeneity of the disease. The current definitions of Lupus Low Disease Activity State (LLDAS) according to the Asia Pacific Lupus Collaboration (APLC) and remission according to Definition of Remission in SLE (DORIS) 2021 are difficult to achieve and maintain over time.ObjectivesTo evaluate the concordance between the LLDAS and the clinical status according to the rheumatologist opinion and reasons of disagreement. To explore modifications in LLDAS definition that best fit with the expert´s opinion.MethodsProspective multicenter study of SLE patients (ACR 1997 Classification Criteria or clinical diagnosis by the physician) from seven Spanish Rheumatology Departments. Statistical analysis: descriptive cross-sectional (at the time of recruitment) analysis of the demographic and clinical characteristics, treatments; remission and LLDAS and the subjective evaluations of SLE activity by the rheumatologist. Analysis of the level of agreement between expert opinion and the definition of LLDAS and its modification were evaluated using Cohen’s kappa.ResultsDEMOGRAPHIC, DISEASE CHARACTERISTICS AND TREATMENTS. Five hundred and eight were included (92% women; mean age (±SD): 50.4 years (±13.7)). Mean SLEDAI-2K (±SD) was 2.84 (±3.31). A total of 406 (79.9%) patients presented SLEDAI-2K≤4. A total of 317 (74.1%) patients were on antimalarial treatment. Two hundred and twenty-two (43.7%) patients were on some type of immunosuppressive or biological therapy. More than half of patients were not taking glucocorticoids (n=310, 61%). A total of 38 patients (7.5%) were taking doses of prednisone higher than 7.5mg/day.REMISSION/LLDAS 267 (54.4%) patients were in remission and 304 (62.7%) patients were in LLDAS. According to the expert opinion of the rheumatologist, remission was the most frequent state considered (n=206, 41.6%); followed by low activity (n=153, 30.9%); serologically active (n=71, 14.3%); moderate activity (n=55, 11.1%) and high activity (n=10, 2%).AGREEMENT Overall agreement between expert opinion and the definition of LLDAS was 71.4 % with a Cohen’s kappa of 0.3. The majority of the cases (96.1%) that fulfilled the definition of LLDAS, were classified by the expert as remission, serologically active or low activity. Only 12 (3,9%) patients were classified by the expert as moderate or high activity. Of the patients that did not fulfill the definition of LLDAS, 126 out of 179 (70.4%) patients were classified by the expert as remission/low disease activity (Figure 1). The main reasons for discordance in the group that did not fulfill the definition of LLDAS were the presence of new clinical features compared to previous visit and a SLEDAI 2-K >4, in 74 (58.7%) and 59 (46.8%) patients, respectively. The LLDAS adjustment that meant a significant increase in the agreement was the exclusion of the comparative features with the previous visit, with an increase in the agreement to 82.6% (95% CI: 81.61-83.96%). The modification of prednisone to 5mg/daily dose, did not represent a significant change in agreement from the original definition.Figure 1.Comparison of LLDAS and expert opinionConclusionAt a given point in time, almost two thirds of SLE patients were in remission or in LLDAS. There is a good correlation between LLDAS and the physician’s opinion, particularly for those patients who fulfill LLDAS definition. However, the agreement is not so good for patients who don’t, these being excessively classified by the physician as remission or low activity. The main LLDAS items causing this disagreement were a SLEDAI-2K >4 and the appearance of different clinical manifestations from the previous evaluation. On the contrary, physician assessment by the PGA adequately fits the LLDAS definition. The modification of the LLDAS definition excluding the comparison with previous assessment increases the agreement with the expert opinion to 82.6%.Disclosure of InterestsNone declared

Background:Factors associated with the development of chronic heart failure (CHF) in systemic lupus erythematosus (SLE) have received little attention. On the other hand, recent data from the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection during the COVID19 pandemic have cast some doubts on its cardiological safety.Objectives:To identify factors associated to CHF in SLE.Methods:Retrospective cross-sectional study, including all patients with SLE (≥4 ACR-1997 criteria) recruited in RELESSER registry. The objectives and methodology of the registry have been described previously (1). CHF was defined according to the Charlson index item. Patients with CHF before diagnosis of SLE were excluded. Cumulative damage was measured with the SLICC/ACR index, excluding cardiovascular (CV) items (mSDI). Multivariate analysis exploring factors associated with CHF was carried out.Results:117 patients (3% of the entire cohort) with SLE and CHF and 3,506 controls with SLE without CHF were included. 90% were women. Disease duration: mean (SD), 120.2 (87.7) months. CHF appeared after a median (P25-P75) of 9.40 (4.2-18.3) years from SLE diagnosis. Patients with CHF were older (59.8 ± 18.2 vs. 46.2 ± 4.3). In the bivariate analysis, the association of CHF with greater severity [Katz severity index: median (IQR): 4 (3-5) vs. 2 (1-3)], damage [mSDI: 3 (2-4) vs 0 (0-1)], comorbidity [modified Charlson- excluding CV items: 4 (3-6) vs 1(1-3)] and both CV (37.5% vs 6.7%) and overall mortality (43.2% vs 4.7%) (pTable 1.Congestive heart failure associated factors (multivariable analysis)Odds Ratio95% CIP-valueSex (female)0.460.25 - 0.880.0147Ischaemic cardiopathy7.964.01 - 15.48Cardiac arrhythmia7.384.00 - 13.42Pulmonary hypertension3.711.84 - 7.250.0002Cardiac valvulopathy6.333.41 - 11.62Hospitalization (due to SLE)3.741.81 - 8.650.0008Calcium or vitamin D5.292.07 - 16.860.0015Antimalarials0.280.17 - 0.45mSDI *1.291.16 - 1.44*mSDI = modified SLICC/ACR damage index (without cardiovascular items)Conclusion:- CHF is a rather late complication of SLE.- Patients with SLE and CHF have more severe SLE, with greater refractoriness to SLE treatments and higher overall mortality.- Treatment with antimalarials, as routinely used in SLE patients, is not only safe to heart, but even appears to have a cardioprotective effect.References:[1]Rúa-Figueroa I, López-Longo FJ, Calvo-Alén J, et al. National registry of patients with systemic lupus erythematosus of the Spanish Society of Rheumatology: objectives and methodology. Reumatol Clin. 2014;10(1):17-24.Acknowledgements:Research Unit of Spanish Society of RheumatologyDisclosure of Interests:None declared

Background:Biological disease modifying drugs (bDMARD) has allowed a targeted approach to rheumatoid arthritis (RA). Once sustained remission is achieved, the use of bDMARDs at lower doses than indicated in data sheets is considered (optimized treatment, OT). Studies show that 33-64.2% of patients on OT lose remission in the first 6 months. Still, it is a feasible practice in selected patients.Objectives:We aimed to describe demographic, clinical, analytical and therapeutic characteristics of RA patients on OT in our hospital. Secondly, we wanted to study the survival of OT and to compare patients with survival longer or shorter to one year.Methods:We did a retrospective review of the medical records of RA patients who began OT between January 2014 and December 2018. We included patients on Abatacept(ABA), anti-TNF drugs and Tocilizumab (TCZ). We defined the end of OT as the restart of the usual dose. Continuous variables are described with mean and standard deviation (SD) and qualitative variables are shown in absolute value and percentage. We divided the sample into patients with OT survival greater than or equal to one year and patients with OT survival less than one year, after which the characteristics of both populations were compared. Categorical variables were analyzed using Pearsons chi and quantitative variables using Student’s t-test. Survival analysis was performed using a Kaplan-Meier estimator.Results:We identified 234 RA patients on bDMARD at our hospital, of which 53 (22.6%) had been optimized between January 2014 and December 2018: 39 (73.6%) with anti-TNF, 7 (13.2) with ABA and 7 (13.2%) with TCZ. Their characteristics are shown in table 1. It is worth mentioning the rate of monotherapy (43.3%)and the low number of bDMARD prior to optimization (median 0.71, SD 0.97). The median survival of OT was 33.8 months and thirty-nine patients (73.6%) maintained OT for at least one year (95%confidence interval, 0.59 to 0.83). When comparing patients with survival greater/equal versus shorter to one year (table 2), the only variable showing significant differences was the presence of erosions at beginning of OT (28 patients in the >1 year group vs 7 in the < 1 year group; p=0.012). Although the difference is not significant (p = 0.07), patients with a survival of less than one year had more time between the debut of disease and the beginning of the first conventional synthetic DMARD (csDMARD).Table 1.Characteristics of the sample (N=53)Female40 (75.47%)Age at diagnosis (years)49.54 (11.68)Active smoker15 (33.33%)ACPA positive36 (67.92%)mRF positive44 (83.02%)Nodules11 (20.75%)Extra-articular disease11 (20.75%)Erosions*35 (74.47%)Monotherapy at optimization23 (43.4%)bDMARD* previous to OT0.71 (0.97)Optimized bDMARD•ETN20 (37.74%)•ADA16 (30.19%)•ABA7 (13.21%)•TCZ7 (13.21%)•GOL2 (3.77%)•CZB1 (1.89%)DAS28 at•Diagnosis4.88 (1.25)•Beginning – 1st sDMARD4.62 (1.6)•Beginning – 1st bDMARD4.98 (1.06)•Beginning – opt bDMARD4.67 (1.17)•Optimization1.88 (0.65)Months from diagnosis to introduction of 1st sDMARD*19.67 (35.01)Months from disease debut to low activity*38.75 (30.34)Months in low activity until start of OT23.73 (22.47)ACPA: anti-citrullinated protein antibodies; mRF: monoclonal rheumatoid factor; Erosions: presence of erosions at Optimization; bDMARD: biological DMARD; ETN: Etanercept; ADA: Adalimumab; ABA:Abatacept; TCZ:Tocilizumab; GOL:Golimumab; CZB:Certolizumab; Opt bDMARD: bDMARD optimized; csDMARD: conventional synthetic DMARD; Low activity: DAS28 < 3.2Conclusion:OT is a therapeutic option from which some patients could benefit. Maintenance of OT may be related to early start of DMARDs. More studies are needed to define the characteristics of patients who can safely benefit from OT.References:[1]Henaux S et al. Risk of losing remission, low disease activity or radiographic progression in case of bDMARD discontinuation or tapering in rheumatoid arthritis: systematic analysis of the literature and meta-analysis. Ann Rheum Dis 2018;77:515–522.Disclosure of Interests:None declared

Background:Giant cell arteritis (GCA) presents with visual symptoms in approximately 37%1of patients at diagnosis. Patients with visual symptoms present, according to some series, lower levels of C-reactive protein (CRP) at diagnosis and associate less headache, fever, cranial nodules or polymyalgia (PM).Relapses despite glucocorticoid treatment (GC) are frequent (40-60%). Visual symptoms are very rare in relapses (0% in several series). Since most series focus on northern European populations, it is interesting to study the characteristics in our population.Objectives:To describe visual manifestations in both diagnosis and recurrence of stroke, only in patients diagnosed with temporal artery biopsy. To analyze demographic, clinical and analytical features in patients with and without visual symptoms.Methods:We retrospectively reviewed the medical records of patients with positive biopsy for GCA at our center from January 2000 through December 2018. Relapse was defined as the appearance of clinical symptoms in a previously asymptomatic patient requiring a dose increase or restart of GCS. Patients with no response to GCS were not included. Qualitative variables are shown with absolute value and percentage and quantitative variables with mean and standard deviation (SD). Kruskal Wallis, Fisher test and Mann-Whitney U test were used for bivariate analysis.Results:52 patients were found: 39 women (73.6%), with an average age at diagnosis of 77.6 years (SD 6.3). At diagnosis, 28 presented visual symptoms (53.84%): oculomotor paralysis 5 (9.61%), amaurosis fugax 8 (15.38%), blindness 6 (11.54%), decreased visual acuity 8 (28.57%) and other visual symptoms 1 (1.92%). Eleven had monocular symptoms (38%) and 9 binocular (32%), in 10 patients this data was not collected. The symptoms were permanent in 11 (39.2%) despite GC. Type of visual impairment was: Anterior Ischemic Optic Neuropathy (AION) (12, 42.86%), impairment of cranial pairs (5, 17.86%), central retinal artery occlusion (1, 3.57%), cilioretinal artery occlusion (1, 3.57%) and Posterior Ischemic Optic Neuropathy (1, 3.57%).Of the 52 patients, 17 (32.69%) presented a minimum of one recurrence and 3 (5.77%) presented 2 or more. No patient relapsed with visual clinic.There were no differences among patients with and without visual symptoms in the variables studied (table 1). However, patients with visual symptoms at diagnosis had numerically less PM and cranial nodules.Table 1.Demographic, clinical and analytical differences between patients with/without visual symptomsVariablesWith visual symptoms (28)Without visual symptoms (24)ESR >5017 (60.7%)15 (62.5%)ESR 4 (14.3%)2 (8.33%)CRP>1017 (60.7%)13 (54.16%)CRP 3 (10.7%)2 (8.33%)Cephalea24 (85,7%)23 (95,8%)Polymyalgia9 (32,1%)12 (50%)Constitutional syndrome9 (32,1%)7 (29,1%)Jaw claudication17 (60.7%)12 (50%)Cranial nodules4 (14,3%)8 (33,3%)Sex: Man/Woman9/195/19Previous PM diagnosis4 (14,3%)3 (12,5%)Conclusion:In our series, 53% of the patients presented visual symptoms at diagnosis, a number higher than that described in the literature. It is important to remember that only patients with biopsy-confirmed ACG were included. The most frequent manifestations were AION followed by oculomotor paralysis. A numerically lower percentage of PM and cranial nodules was observed at diagnosis in patients with visual symptoms compared to patients without them, as seen in some series. The absence of visual clinic in recurrences coincides with that reported in the available literature.References:[1]Alba M et al. Relapses in Patients With Giant Cell Arteritis Prevalence, Characteristics, and Associated Clinical Findings in a Longitudinally Followed Cohort of 106 Patients. Medicine. 2014;93: 194–201.Disclosure of Interests:None declared

Background:The Hemophagocytic Syndrome (HPS) is has been classified into 2 groups: primary and secondary. The secondary form is mainly associated with hemato-oncological diseases (HOD) and autoimmune diseases (AID). The present work aims to obtain clinical and analytical data that can guide us to an etiological diagnosis.Objectives:To describe and identify the differences between HPS secondary to AID and HOD during their admission to a tertiary hospital between 2005 and 2019.Methods:This is a retrospective observational study. We include patient meeting the diagnostic criteria for HLH proposed by Henter JI. (1), or who presented haemophagocytic cells (HC) in the bone marrow biopsy (BMB), or who had HPS in the hospital discharge report. Demographic, clinical, analytical, etiological, underlying disorders and prognosis variables were collected. Continuous variables are described with the mean or median according to the degree of normality. Kruskal Wallis, Fisher test and Mann-Whitney U test were used for the bivariate analysis, and also a multivariate logistic regression analysis was performed.Results:We found 30 patients with secondary HPS, 22 of which corresponded to the AID [Systemic Lupus Erythematosus (n=5), Adult Still’s Disease (n=3), Rheumatoid arthritis (n=1) and IgG4 Sclerosing Disease (n=1)] and HOD [Non-Hodgkin’s Lymphoma (n=3), Myelodysplastic syndrome (n=3), Acute leukemia (n=3), Extranodal NK cell lymphoma (n=1), Multiple Myeloma (n=1) and probable lymphoproliferative process (n=1)]. The coincidence of an infectious disease with HPS was observed in 8 of the 22 cases [AID: 5 cases (2Cytomegalovirus, 2 viral respiratory infections and 1 bacterial infection) and HOD: 3 cases (2Epstein Barr virusand 1 bacterial infection)]. In two patients with HPS secondary to HOD (acute leukemia), allogeneic transplantation was associated as a possible trigger. In a patient with myelodysplastic syndrome, HPS was associated with the development of graft versus host disease. The age at diagnosis was lower in the AID [40 (26.5 - 56.3); p 0.001]. The HOD had more severe cytopenias [platelets 4500 (650 - 15,750; p 0.009), leukocytes 2050 (20 - 728; p 0.0001) and neutrophils 0 (0 - 280; p 0.002)]. Overall mortality (n=30 patients) was 43.3% (HOD: 66.7%; p 0.029) (table 1). In the final multivariate model according to AID and HOD, the following independent associations were observed: age (p 0.002), platelets (p 0.031), GOT (p 0.012), GPT (p 0.015), total proteins (p 0.007) and mortality (p 0.007).Table 1.Characteristics and comparative analysis of HPS secondary to AID and HODTotalAIDHODn301012*pAge(x± s)55,5±18,34026,5-56,36857,5-73,80,001Gender, male1446,7%330%975%0,084Spenomegaly1653,3%550%866,7%0,666Hepatomegaly1033,3%440%433,3%1,000Hb (g/dL)7,16,4-7,97,26,6-8,46,55,9-7,30,05Pt (x109/L)13 5005 000-52 50031 65011 000-100 2504 500650-15 7500,004Leu (x109/L)1 250238-3 1531 9851 350-3 38218520 – 7280,000Neu (x109/L)6150-1 550948633-1 80800-2800,001Fb (mg/dL) (n=24)171111-35821290-450167114-3541,00Fer (ng/mL) (n=28)15 3305 434-38 28414 2634 254-14 26316 7968 287 - 56 9690,314Tg (mmol/L)341226-438411,5234-572321233,8-403,80,314GOT (U/L)13978-406457289-1 14010671-1930,003GPT (U/L)16246-388432174-59910954-2630,017T.P. (n=29)4,8±,1,045,04,5-5,84,33,9-4,50,003Hospital stay35,520,0-60,830,59,5-53,361,529,3-93,30,036Hospital stay pre-dx16,58,5-29,8105,0-16,52610-390,038Mortality1343,3%110%866,7%0,011Hb: hemoglobin, Pt: platelets, Leu; leukocytes, Neu, neutrophils, Fb: fibrinogen, Fer: ferritin, Tg: triglycerides, GOT: aspartate aminotransferase, GPT: alanine aminotransferase, T.P.: total proteins, pre-dx: prior to the diagnosis of HPS according to BMO. *Analysis between AID and HOD.Conclusion:The HOD presented higher mortality and severe cytopenias. The AID presented a higher elevation of transaminases and better prognosis.References:[1]Henter JI, et al. HLH-2004: Diagnostic and therapeutic guidelines for HLH.Pediatr Blood Cancer. 2007;48:124.Disclosure of Interests:César Antonio Egües Dubuc: None declared, Andrea De Diego: None declared, Patricia Cabrera Miranda: None declared, Nerea Alcorta Lorenzo: None declared, Jesús Alejandro Valero Jaimes: None declared, Jose Ramon Furundarena Salsamendi: None declared, Luis Maria Lopez Dominguez: None declared, Jorge Jesús Cancio Fanlo: None declared, Olga Maiz-Alonso: None declared, Esther Uriarte Isacelaya: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Joaquin Maria Belzunegui Otano: None declared

Background:The Hemophagocytic Syndrome (HPS) had a mortality rate between 20% and 90%. The mortality of HPS secondary to autoimmune diseases (AID) is lower than hemato-oncological diseases (HOD). In general, the HOD, thrombocytopenia, age, and a prolongation of prothrombin are considered to be an adverse prognostic factor.(1)Objectives:To describe and identify differences between patients who survived and did not survive to HPS during hospital admission to a tertiary hospital between 2005 and 2019.Methods:This is a retrospective observational study. All patients who met the diagnostic criteria for LHH were included, or who presented haemophagocytic cells in the bone marrow biopsy, or who had diagnosis of HPS in the hospital discharge report.(2) Demographic, clinical, analytical, etiological, underlying disorder and prognosis variables were collected. Continuous variables are described with the mean or median according to the degree of normality. Kruskal Wallis, Fisher test and Mann-Whitney U test were used for the bivariate analysis, and also a multivariate logistic regression analysis was performed.Results:Thirty patients with HPS were included. They were distributed in 5 subgroups (Table 1). Overall mortality was 43.3%, statistically significant higher in the HOD [8 patients (66.7%); p 0.029]. Also, they were divided into 2 groups (survivor vs. non-survivor; Table 2). In the multivariate model the age and INR prolongation were confirmed to be independently associated with the outcome of mortality.Table 1.Etiology of HPSEtiologyn = 30MortalityAID10n = 1 Systemic lupus erythematosus51 Adult Still’s Disease3No Rheumatoid arthritis1No Sclerosing Disease IgG41NoHOD12n = 8* Non-Hodgkin’s lymphoma31 Myelodysplastic syndrome32 Acute leukemia33 Extranodal NK cell lymphoma11 Multiple Myeloma1No Probable lymphoproliferative process11Infectious diseases2n = 1 Pneumocystis carinii in patient with H.I.V.11 Campylobacter yeyuni1NoGlyoblastoma multiforme with temozolomida1n = 0HPS without defined aetiology53HIV: Human Immunodeficiency Virus, NK: Natural Killer. *p = 0,029Table 2.Characteristics and differences between survivor and non-survivor groupsTotalNon-survivorsurvivorn301317pAge55,5±18,36858,2-74,54034-570,043Women1653,3%761,5%947,1%1,00Comorbidities (≥ 2)516,7%215,4%317,6%1,000Hospital stay35,520-60,82915,5-39138-170,563Splenomegaly1653,3%753,8%952,9%1,000Hepatomegaly1033,3%538,5%529,4%0,705Hb (g/dL)7,16,4-7,9710%6,2-7,87,16,6-7,80,094Pt (x109/L)13 5005 000-52 50016 00011 000-44 00012 0005 000-99 0000,281Pt≤ 100 0002583,3%13100%1270,6%0,052Leu (x109/L)1 250238-3 1531 300150-3 9401 400200-3 3400,457Neu (x109/L)6150-1 5501 29020-3 3006500-1 4000,805Fb (mg/dL) (n=24)171111-358167,00106-253169,00103-4510,796Fer (ng/mL) (n=28)15 3305 434-38 28429 0635 728-74 60413 2258 287-28 7290,108Tg (mmol/L)341226-438254,00184-382471,00341-6040,053GOT (U/L)13977,5-406,3133,00101-513179,00101-512,50,483GPT (U/L)16246-389109,0041-333199,0099-2980,198INR (n=29)1,51,1-1,92,11,2-3,71,51,1-1,60,028Hb: Hemoglobin, Pt: platelets, Leu: leukocytes, Neu: neutrophils, Fb: fibrinogen, Fer: ferritin, Tg: triglycerides, GOT: aspartate aminotransferase, GPT: alanine aminotransferaseConclusion:The HOD presented higher mortality. The non-survivor group presented a longer INR prolongation and a higher age at the time of diagnosis.References:[1]Parikh SA. Prog. factors and outcomes of adults with HLH. Mayo Clin Proc. 2014;89:484–492.[2]Henter JI. HLH-2004: Diag. and therapeutic guidelines for HLH.Pediatr Blood Cancer. 2007;48:124.Disclosure of Interests:César Antonio Egües Dubuc: None declared, Andrea De Diego: None declared, Patricia Cabrera Miranda: None declared, Nerea Alcorta Lorenzo: None declared, Jesús Alejandro Valero Jaimes: None declared, Jose Ramon Furundarena Salsamendi: None declared, Olga Maiz-Alonso: None declared, Luis Maria Lopez Dominguez: None declared, Esther Uriarte Isacelaya: None declared, Jorge Jesús Cancio Fanlo: None declared, Jaime Calvo Grant/research support from: Lilly, UCB, Consultant of: Abbvie, Jansen, Celgene, Joaquin Maria Belzunegui Otano: None declared

Background:Biological therapies have revolutionized the management of rheumatic diseases. This study analyzes the paradoxical autoimmune inflammatory manifestations that these therapies can induce. They are described as paradoxical because these are diseases in which the same biological drugs have proven effective.Objectives:The aim of this study is to carry out a descriptive analysis of paradoxical biologics-induced autoimmune manifestations.Methods:A retrospective research was carried out during January 2017 and March 2018 at Hospital Universitario Donostia.Computerized medical records were reviewed. The following variables were recorded: underlying disease; type of developed manifestation; the triggering biologic drug and its duration; concomitant treatment with disease-modifying antirheumatic drugs (DMARDs), previous biological treatments; the adopted measure and the resolution of the complication or not.Qualitative variables are recorded in absolute value and in percentage. The quantitative variables are recorded with the mean and standard deviation. The data has been analyzed with the SPSS Statistics 20 program.Results:Twenty-six cases were analyzed. The most common triggering drugs were infliximab (30.8%), adalimumab (30.8%) and etanercept (15.4%). The most common underlying diseases were spondyloarthritis (42.3%), rheumathoid arthritis (34.6%) and Crohn’s disease (11.5%). The most developed complications were cutaneous affectations (76.9%), psoriasis specifically.Statistical significative difference regarding the molecules causing the complication, has only been found in the previous use of biologic drugs (p 0.003), number of treatment dropouts (p 0.048) and number of resolved complications (regardless of the adopted measure) (p 0.041).Conclusion:Infliximab and adalimumab are the drugs that presented the most paradoxical manifestations, probably because they are the oldest and most used ones. The difference found in previously used biologics, could be due to the fact that new drugs are less frequently presented as the first option. Psoriasis is the most frequently developed complication. The difference found in the number of abandonments of the biologic treatment and the solution of the complication might be more associated with the complication itself, rather than with the responsible molecule. There is no consensus on the measures to be taken when facing the complication. The severity of the manifestation should be assessed, as well as the control of the underlying disease. Most complications resolve overtime.Table 1Infliximabn 8 (31.8%)Adalimumabn 8 (30.8%)Etanerceptn 4 (15.4%)Certolizumabn 2 (7.7%)Golimumabn 2 (7.7%)Abataceptn 1 (3.8%)Tocilizumabn 1 (3.8%)Totaln 26 (100.0%)p valueUnderlying disease0.789Rheumatic (%)6 (75.0)5 (62.5)4 (100.0)2 (100.0)2 (100.0)1 (100.0)1 (100.0)21 (80.0)Digestive (%)2 (25.0)3 (37.5)000005 (19.2)Type of developed manifestation0.235Hematologic (%)01 (12.5)000001 (3.8)Neurologic (%)2 (25.0)0000002 (7.7)Digestive (%)00001 (50.0)001 (3.8)Cutaneous (%)6 (75.0)6 (75.0)4 (100.0)2 (100.0)1 (50.0)01 (100.0)20 (76.9)Other (%)01 (12.5)0001 (100.0)02 (7.7)Table 2Infliximabn 8Adalimumabn 8Etanerceptn 4Certolizumabn 2Golimumabn 2Abataceptn 1Tocilizumabn 1Totaln 2p valueThe triggering biologic drug and its duration (months)43.25(SD 44.81)10.9375.50(SD 66.08)4.5011.006.005.0030.660.635Concomitant treatment with DMARDs (%)2 (25.0)2 (25.0)1 (25.0)1 (50.0)001 (100.0)7 (26.9)0.811Previous biological treatment (%)02 (25.0)1 (25.0)2 (100.0)2 (100.0)1 (100.0)1 (100.0)9 (34.6)0.003Suspension as the adopted measure (%)5 (62.5)7 (87.5)02 (100.0)1 (50.0)1 (100.0)1 (100.0)17 (65.4)0.048Resolution of the complication (%)3 (37.5)8 (100.0)1 (25.0)1 (50.0)1 (50.0)1 (100.0)1 (100.0)16 (64.0)0.041Disclosure 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, Iñigo Rua-Figueroa: None declared, Elvira Diez Alvarez: None declared, Cristina Bermúdez: None declared, Francisco J López-Longo Grant/research support from: AbbVie and GSK, Speakers bureau: AbbVie, Actelion, Bristol Myers Squibb, GSK, MSD, Pfizer, Roche, and UCB Pharma, María Galindo-Izquierdo: None declared, Alejandro Olive: None declared, Eva Tomero Muriel: None declared, Antonio Fernandez-Nebro: None declared, Mercedes Freire González: None declared, Olaia Fernández- Berrizbeitia: None declared, Ana Pérez Gómez: 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. Rodíguez-Gómez: None declared, Paloma Vela-Casasempere: None declared, Alina Boteanu: None declared, J. Narváez: None declared, Victor Martinez Taboada: None declared, Blanca Hernández-Cruz Speakers bureau: Abbvie, Lilly, Sanofi, BMS, STADA, José Luis Andreu: None declared, José A Hernandez Beriain: None declared, Lorena Expósito: None declared, Raúl Menor-Almagro: None declared, Mónica Ibañez Barceló: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Carles Galisteo: None declared, Enrique Raya: None declared, Víctor Quevedo Vila: None declared, Tomas Vazquez Rodriguez: None declared, Jesus Ibañez: None declared, Jose M Pego-Reigosa: None declared

Objectives To investigate the primary respiratory manifestations (PRM) in SLE. Methods All patients in the RELESSER cohort were retrospectively investigated for the presence of PRM Results At least one PRM was present in 11.3% (365/3215) of cases. The most common was pleurisy, occurring in 21.1% of patients, followed by ALP in 3.6%, PE in 2.9%, PPH 4%, DILD in 2%, DAH in 0.8%, and SLS in 0.8%. The variables associated with the presence of PPM are shown in the following table 1: Conclusions PPM independently contributed to a decreased survival in SLE Disclosure of Interest None declared

Background Systemic Lupus Erythematosus (SLE) is an autoimmune systemic rheumatic disease that, in our area, presents hematologic manifestations in approximately 70% of cases1. Some of them are very rare so there are no large series whose analysis could provide relevant information. Objectives To study the characteristics of patients with Hemophagocytic Syndrome (HS) in a large sample of SLE patients. Methods SLE patients from RELESSER database were studied. We analysed SLE manifestations present at 12 different domains (mucocutaneous, renal, musculoskeletal, constitutional, hematologic, vascular, cardiac, respiratory, neuropsychiatric, gastrointestinal, ophthalmic and serological) before, during and after HS diagnosis and until the last available assessment. We also studied activity (SELENA-SLEDAI) and damage (SLICC/ACR DI) indices at those moments.We evaluated the treatment received, HS recurrences and the number of deaths by this entity. Results 3,656 SLE patients (≥4 ACR criteria) from 45 Rheumatology Units across Spain were studied. Seven patients ( Clinically, 100% of the patients presented fever and alterations of the liver profile, 85.8% cytopenias and 71.5% dermatological manifestations. Respiratory manifestations and hemolytic anemia were present in 57.2% of the cases, both; lymph nodes and coagulopathy in 42.9%. Hepatomegaly was detected in 28.6%, as well as neuropsychiatric, digestive and renal manifestations. Splenomegaly was detected in 14.3%. The mean hemoglobin level was 8.6 (± 1.1) g/dl, platelets 85,585 (± 83,390)/mm3, ferritin 7,410 (± 6,470) ng/ml and triglycerides 404.7 (± 235.6) mg/dl. All patients were admitted and undergonebone marrow study, requiring a mean of 2.2 (± 1.5) treatment lines, using 2.8 (± 1.7) drugs. One patient died during the HS episode by the HS itself and another 2 patients had 2 and 3 recurrences, respectively. The following table shows the characteristics of each patient. Conclusions HS is a rare life-threatening SLE manifestation. It must be suspected in SLE patients with persistent fever who do not respond to antibiotics, cytopenias and evidence of multiorgan involvement. Relapses and death are common in HS associated to SLE. References Pego-Reigosa JM, Rua-Figueroa I, Lopez-Longo FJ, Galindo-Izquierdo M, Calvo-Alen J, Olive-Marques A, et al. Analysis of disease activity and response to treatment in a large Spanish cohort of s with systemic lupus erythematosus. Lupus 2015;24:720–9. Acknowledgements Work supported by Spanish Society of Rheumatology, FIS/ISCIII (PI11/02857), BIOCAPS from the European Union 7th Framework Programme/REGPOT-2012–2013.1 (316265), GSK, Roche, Novartis, UCB. Disclosure of Interest None declared

Objectives The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. Methods We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. Results A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3–17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. Conclusions A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE.

Background Secondary macrophage activation syndrome (MAS) is a group of diseases, especially due to autoimmune (AI) and hemato-oncology (HO). It would be interesting to find any clinical and analytics data to differentiate both etiologies. Objectives To describe and compare demographics, clinical and laboratories features and mortality of patients diagnosed with secondary MAS due to HO and AI diseases at the Donostia University Hospital. Methods A cohort of patients diagnosed with MAS was studied by reviewing medical reports in the period Dec/2008-Jan/2015. We analyzed and compared only patients with AI and HO diseases. The variable studied were diagnosis, age, sex, fever, organomegaly, hospital and overall mortality, analytical findings, hospital stay, days from admission to diagnosis and days from diagnosis to the end of the study or death after discharge. Quantitative variables are shown with the median and interquartile range. For the bivariate analysis Wilcoxon and Chi square test were used. Median survival in months and Hazar Ratio (HR) was calculated with the Kaplan Meier plot. Results Nineteen patients were found diagnosed with MAS, 6 and 9 were due to AI and HO diseases respectively. The AI diseases found were: 3 Systemic Lupus Erythematosus, 2 Adult Still9s Disease and 1 disease associated with IgG4. HO diseases found were: 3 acute myeloid leukemias, 2 B cells Not Hogkin Lymphoma (NHL), 1 T anb B cells NHL, 1 Natural Killers cells extranodal lymphoma, 1 myelodysplastic syndrome and 1 gastric plasmacytoma. The table shows the descriptive analysis of 19 patients and the bivariate analysis between AI and HO. The median survival of HO diseases was 1.2 months and AI diseases can not be calculated. The mortality of HO and AI diseases was 77.8% and 16.7% respectively with a p=0.04 in the log rank test. The HR of mortality among HO against AI diseases was 6.84. Conclusions In the present study the following differences were found: 1) Patients with MAS due to AI diseases have a higher elevated liver enzymes compared to HO disease. 2) Patients with MAS due to HO diseases have a greater pancytopenia compared to AI diseases, especially in leukocytes and neutrophils. 3) Patients with MAS due to HO have a higher mortality compared to AI diseases. Disclosure of Interest None declared

Background The secondary macrophage activation syndrome (SMAS) is a group of diseases that include the: Autoimmune (AI), Hemato-Oncological (HO), Infectious (Inf) and Oncological (Onco). We make a review of the the cases presented in a our hospital. Objectives Describe the characteristics demographic, clinical, laboratory, treatment, underlying disorders and mortality of patients diagnosed with SMAS. Methods A cohort was studied retrospectively of patients diagnosed with SMAS between the period December/2008-January/2014 by reviewing medical records from the diagnosis until January/2014. The nominal variables were: diagnosis, treatments during hospitalization and after discharge. Dichotomous variables were: sex, fever, organomegaly, mortality, admission to the Intensive Care Unit (ICU) and recurrence of SAMS. Quantitative variables were: age, laboratory findings, hospital stay, days from admission to the bone marrow biopsy (BMB). Patients were divided into 4 groups (AI, HO, Inf and Onc). The variables were analyzed between the 4 groups and between AI and HO. Quantitative variables showed asymetric distribution so it showed with the median and interquartile range. For the bivariate analysis the Kruskal-Wallis, Pearson Chi Square and Fisher9s Exact tests were used. Results 13 patients (6 female) with median age of 54 (32-63) were found: 5 with AI diseases (2 Systemic Lupus Erythematosus, 2 Adult Still9s Disease and 1 IgG4 associated disease), 5 HO diseases (3 Non Hogkin Lymphoma, 1 acute myeloid leukemia and 1 Lymphoma of Natural Killers cells), 2 Inf. diseases (Campylobacter jejuni and human immunodeficiency virus) and 1 Onc. disease (Chemotherapy in Glioblastoma multiforme). Table shows the descriptive and bivariate analysis of the most important variables. The treatments used were: glucocorticoids in all patients, immunoglobulins in 8 (3 AI, 2 HO, 2 Onc. and 1 Inf.), Cyclosporine in 8 (5 AI and 3 HO), anakinra in 4 (2 HO and 2 AI), tocilizumab and chemotherapy in 2 HO. Conclusions We found that leukopenia was lower in AI disease than HO diseases with statistically significant p. AI diseases had worse prognosis, increased mortality and hospital days than other diseases. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5055