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Background Over the month of April, Spain has become the European country with more confirmed cases of COVID-19 infection, after surpassing Italy on April 2nd. The community of Castile and León in Spain is one of the most affected by COVID-19 infection and the province of León has a total of 3711 cases and 425 deaths so far. Rheumatic patients should be given special attention regarding COVID-19 infection due to their immunocompromised state resulting from their underlying immune conditions and use of targeted immune-modulating therapies. Studying epidemiological and clinical characteristics of patients with rheumatic diseases infected with SARS-CoV2 is pivotal to clarify determinants of COVID-19 disease severity in patients with underlying rheumatic disease. Objectives To describe epidemiological characteristics of patients with rheumatic diseases hospitalized with COVID-19 and determine risk factors associated with mortality in a third level Hospital setting in León, Spain. Methods We performed a prospective observational study, from 1st March 2020 until the 1st of June including adults with rheumatic diseases hospitalized with COVID-19 and performed a univariate and multivariate logistic regression model to estimate ORs and 95% CIs of mortality. Age, sex, comorbidities, rheumatic disease diagnosis and treatment, disease activity prior to infection, radiographic and laboratorial results at arrival were analysed. Results During the study period, 3711 patients with COVID-19 were admitted to our hospital, of whom 38 (10%) had a rheumatic or musculoskeletal disease. Fifty-three percent were women, with a mean age at hospital admission of 75.3 (IQR 68–83) years. The median length of stay was 11 days. A total of 10 patients died (26%) during their hospital admission. Patients who died from COVID-19 were older (median age 78.4 IQR 74.5–83.5) than those who survived COVID-19 (median age 75.1 IQR 69.3–75.8) and more likely to have arterial hypertension (9 [90%] vs 14 [50%] patients; OR 9 (95% CI 1.0–80.8), p 0.049), dyslipidaemia (9 (90%) vs 12 (43%); OR 12 (95% CI 1.33–108), p 0.03), diabetes ((9 (90%) vs 6 (28%) patients; OR 33, p 0.002), interstitial lung disease (6 (60%) vs 6 (21%); OR 5.5 (95% CI 1.16–26), p 0.03), cardiovascular disease (8 (80%) vs 11 (39%); OR 6.18 (95% IC 1.10–34.7, p 0.04) and a moderate/high index of rheumatic disease activity (7 (25%) vs 6(60%); OR 41.4 (4.23–405.23), p 0.04). In univariate analyses, we also found that patients who died from COVID-19 had higher hyperinflammation markers than patients who survived: C-reactive protein (181 (IQR 120–220) vs 107.4 (IQR 30–150; p 0.05); lactate dehydrogenase (641.8 (IQR 465.75–853.5) vs 361 (IQR 250–450), p 0.03); serum ferritin (1026 (IQR 228.3–1536.3) vs 861.3 (IQR 389–1490.5), p 0.04); D-dimer (12,019.8 (IQR 843.5–25,790.5) vs 1544.3 (IQR 619–1622), p 0.04). No differences in sex, radiological abnormalities, rheumatological disease, background therapy or symptoms before admission between deceased patients and survivors were found. In the multivariate analysis, the following risk factors were associated with mortality: rheumatic disease activity (p = 0.003), dyslipidaemia (p = 0.01), cardiovascular disease (p = 0.02) and interstitial lung disease (p = 0.02). Age, hypertension and diabetes were significant predictors in univariate but not in multivariate analysis. Rheumatic disease activity was significantly associated with fever (p = 0.05), interstitial lung disease (p = 0.03), cardiovascular disease (p = 0.03) and dyslipidaemia (p = 0.01). Conclusions Our results suggest that comorbidities, rheumatic disease activity and laboratorial abnormalities such as C-reactive protein (CRP), D-Dimer, lactate dehydrogenase (LDH), serum ferritin elevation significantly associated with mortality whereas previous use of rheumatic medication did not. Inflammation is closely related to severity of COVID-19.Key Points• Most patients recover from COVID-19.• The use of DMARDs, corticosteroids and biologic agents did not increase the odds of mortality in our study.• Rheumatic disease activity might be associated with mortality.

BackgroundThe recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressive patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biologic agents may suppose a risk or protection against SARS-CoV2 infection however, it has been suggested that severe respiratory forms of COVID-19 occur as result of exacerbated inflammation status and cytokine production. This prompted the use of IL-6 (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV2.ObjectivesTo estimate COVID-19 infection rate in patients treated with biologic agents for rheumatic inflammatory diseases, determine the influence of biologic agents treatment as a risk or protective factor and studying the prognosis of rheumatic patients receiving biologic agents compared to general population in a third level Hospital setting in León, Spain.MethodsWe performed a retrospective observational study including patients seen at Rheumatology department who received biological therapy for rheumatic diseases between December 1st 2019 and June 1st 2020 and analysed COVID-19 infection rate. All patients being attended at the rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biologic agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biologic agent and need for hospitalization. We performed a multivariate logistic regression model to assess risk factors of hospital admission.ResultsThere was a total of 3711 patients with COVID-19 requiring hospitalization. 30 patients out of a total of 820 patients (3.6%) receiving biological therapy had contracted COVID-19 and four required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 2.75%, and it was 0.48% among the group with underlying rheumatic diseases. A total of 423 patients died, 2 of which received treatment with biologic agents. Patients who tested positive for COVID-19 were older (female: median age 61.8 IQR 46.5-75; male: median age 68 IQR 48.5-72) than those who were negative for COVID-19 (female: median age 58.4 IQR 48-69; male: median age 55.9 IQR 46-66) and more likely to have cardiovascular disease (27 % vs 10%, OR 3. 41 (CI 1.47 – 7.94), p 0.004), be active smokers (13% vs 5%, OR 3.14 (CI 1.04-9.47), p 0.04) and receiving treatment with IL-12/23 inhibitors (6.7% vs 1.4%, OR 5.06 (CI 1.07-23.91) and rituximab (13% vs 2%, 2.66 (CI 1.03-7.27), p 0.04) and were less likely to be receiving treatment with IL-6 inhibitors (0% vs 14%, CI (0.006-0.97, p ConclusionsOur findings suggest that use of biological therapy does not associate with severe manifestations of COVID-19, and it is likely to have a protective effect against them when compared to the general population.

Background:Rituximab (RTX) is a drug composed of chimeric monoclonal antibodies against the CD20 protein that leads to B cell lymphocyte depletion and is currently licensed for rheumatoid arthritis. There is growing evidence of off-label use of rituximab for severe and refractory systemic autoimmune diseases (SAD).Objectives:Analysing the clinical effectiveness of RTX for SADs such as vasculitis (VS), systemic lupus erythematosus (SLE), systemic sclerosis (SS), primary sjögren syndrome (pSS), necrotizing myopathy (NM) and dermatomyositis (DM) in a rheumatology outpatient clinic in a third level hospital during a 5 year-period (2015 –2020).Methods:We conducted a retrospective analysis of patients with SAD treated with RTX in the last 5 years. We evaluated demographic and clinical data, indication for RXT, previous treatments, cumulative dose of rituximab and corticosteroids, clinical response, and the presence of adverse events. We considered follow-up period between the first and the last clinical evaluation. Clinical response was considered complete with symptom and analytical remission; incomplete with partial symptom or analytical response and no response if there was no symptom or analytical response.Results:35 patients were included (54% women, mean age 60.16 ±17 years). The diagnosis were: pSS (31.4%), SS (17%), SLE (17%), VS (20%), NM (8.8%) and DM (5.8%). Indications for treatment were pulmonary disease in 37% of cases, renal disease in 17%, articular manifestations in 11.4%, haematological manifestations in 14.3%, skin involvement in 8.8%, neurologic manifestations in 5.7% and myopathy in 5.8%. RTX was used after therapeutic failure with previous treatments in 80% (20% of which had receiving treatment with biological disease-modifying antirheumatic drugs) and as first line treatment in only 20% of the cases. After rituximab, 60% of patients had complete response, 17% partial response, and 20% nonresponding. Mean corticosteroid dose post-rituximab was significantly reduced by 60% in pSS (p 0.02), 65% in VS (p 0.03), 50% in SS (p 0.04) and NM (p 0.046). Five patients (14%) had infectious complications, 2 of which needed hospitalization. 7 patients (17%) discontinued therapy, 5 due to ineffectiveness (2 SLE, 1 NM, 1 DM and 1 SS) and 2 patients (14%) due to infectious complications (1 pSS and 1 VS). Patients underwent a median of 2 treatment cycle. The median follow-up after starting RTX was 48.5 (IQR 25.9-74.4) months.Table 1.Clinical characteristicspSSVSSLESSNMDM%31.4%20%17%17%8.8%5.8%Age (years)63.8 (19-73)63.5 (43-82)59.2 (43-78)65.8 (56-78)58.5 (54-63)48.5(26-52)Female100%71%50%66%50%50 %Duration of disease (months)80.5 (24-108)39 (12-60)38.4 (36-90)56.4 (14-96)69 (48-90)60 (25-82)Cumulative RTM dose (g/m2)2.5 (0.75-6)3.2 (0.5-8)1.4 (0.75-5)2.8 (0.5 – 7)1.2 (0.5 – 5)0.56 (0.38-0.75)Complete clinical response63%86%33%71%33%0%Incomplete response18%14%33%14%0%50%No response18%0%33%14%66%50%Glucocorticoid dose (mg/day)Before RTMX12.5 (5-20)21.3 (5-30)9 (0-15)9 (5-15)15 (7.5 – 25)15 (7.5 – 25)Glucocorticoid dose (mg/day)After RTX5 (2.5-15)7.5 (5-15)5 (2.5-15)4.5 (2.5-10)10 (7.5-25)12.5 (8 – 20)ImmunosuppressantsBefore RTX81%71%90%50%33%50%ImmunosuppressantsAfter RTX54%28%57%66%67%50%Severe infusion-related side effects including need for admission0%14%16%0%0%0%Other infusion-related side effects9%29%17%17%0%0%Conclusion:Treatment with RTX was very effective in SADs, particularly in VS, SS and pSS. Further studies are needed to clarify RTX efficacy and safety in SADs, as well as indications and optimal RTX regimens.References:[1]Berghen N, Vulsteke JB, Westhovens R, Lenaerts J, De Langhe E. Rituximab in systemic autoimmune rheumatic diseases: indications and practical use. Acta Clin Belg. 2019 Aug;74(4):272-279.[2]Hofmann K, Clauder AK, Manz RA. Targeting B Cells and Plasma Cells in Autoimmune Diseases. Front Immunol. 2018 Apr 23;9:835.Disclosure of Interests:None declared

Background Denosumab (DB) is a monoclonal antibody to RANK ligand that, like all biological drugs, can be associated with an increased risk of infections. However, there are few studies concerning the risk of infection in these patients treated concomitantly with DB and other biologic drugs. Objectives This study aims at determining whether the treatment with biological drugs and DB combined is associated with an increased risk of adverse effects in patients with autoimmune diseases. Methods Retrospective observational study of patients treated with DB combined with other biological drugs at the Hospital of Leon between 2010–2017. For proper patient selection, the data obtained from the medical prescription program of primary care and the data from the registry of outpatients and walk-in patients of hospital pharmacy were cross-referenced. To determine the increased risk, a control group of patients treated both with bisphosphonates (BF) and with biological agents was selected. The data collected in both groups were: age, sex, diagnosis, comorbidities and other prescribed drugs. Infection, tumour or other adverse effects appeared three months, six months, one year and two years after starting the concomitant treatment. When performing the statistical analysis, it was analysed the time elapsed until the first adverse effect appeared. Results A total n of 28 patients was registered. 16 were treated with BF and biological agents, and 12 were treated with DB and other biological drugs. The prevalence of women was higher in both groups (87.5% BF, 91.7% DB). The mean age at the beginning of the concomitant treatment was similar, being 69.1±8.5 years in the BF group and 69.7±7.1 years in the DB group. All patients treated with DB were diagnosed with RA. Regarding the comorbidities, it seems that those patients treated with DB had fewer CVRF than those treated with BF (68.8% HBP in BF versus 50% in DB, 37.5% dyslipidaemia in BF versus 33.3% in DB). The biological drugs prescribed to be used concomitantly with DB were: 49.7%anti-TNFα, 33.3%rituximab, 8.3%abatacept and 8.3%tocilizumab. In addition, there were no significant differences regarding the application time of the concomitant treatment with biological agents in the BF (35.7±26.7 months) and DB (58.6±43.7 months) groups; being in both groups similar. By comparing both groups, it is observed that those patients treated concomitantly with DB and other biological drugs, have more infections and these appear earlier in time than in patients treated with BF and biological agents (p There were no differences in the appearance of adverse effects in patients with other comorbidities or concomitant treatments. Conclusions It seems that the treatment of DB combined with other biological drugs is associated with a greater number of adverse effects, mainly caused by infections, and having an earlier appearance. More studies and a larger sample would be necessary to confirm this association and to be able to prove the relationship between comorbidities and the use of other concomitant drugs with the appearance of adverse effects. Disclosure of Interest None declared

Background Giant cell arteritis (GCA) can be refractory to corticosteroids1–3. Tocilizumab (TCZ) demonstrated to be effective in two short-term clinical trials. Objectives To assess efficacy of TCZ in refractory GCA or with side effects to corticosteroids in clinical practice. Methods Multicenter study on 134 patients with GCA in treatment with TCZ due to lack of efficacy and/or unacceptable adverse events of previous therapy. Results 134 patients (101 w/33 m); mean age of 73.0±8.8 years. Main clinical features at TCZ onset were: PMR (n=73), constitutional syndrome (n=31), headache (n=70), visual (n=28) and jaw (n=14) affection. Besides steroids, 98 patients also received immunosuppressive agents. table 1 shows evolution during follow-up period. After a median follow-up of 12 [3.7–24] months, it was observed a decrease in:a)CRP from 1.7 [0.4–3.2] to 0.1 [0.0–0.3] mg/dL b)ESR from 33 [14.5–61] to 42–9 mm/1st hour and c) Prednisone dose from 1510–30 to 5 [0–7.5] mg/day. Outcome of patients was:a)discontinuation of TCZ (n=15) due to sustained remission, b)dose reduction due to improvement (n=17) or side effects (n=11), c)withdrawal of TCZ because of side effects (n=12) and d)same dose that at onset (n=73). TCZ had to be discontinued due to: infections, haematological and cardiovascular alterations, neoplasms and heptic toxicity among the most frequent. Table 1 Conclusions TCZ leads to a rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of neutropenia and infection should be kept in mind. References [1] Loricera J, et al. Semin Arthritis Rheum2015;44:717–723. [2] Loricera J, et al. Clin Exp Rheumatol2014;32(3Suppl82):S79–89. [3] Loricera J, et al. Clin Exp Rheumatol2016; 34 (3 Suppl 97):S44–53. Disclosure of Interest None declared

Background The Sjogren syndrome (SS) is an autoimmune disease where the cellular and humoral mechanisms affect the exocrine glands. In 2016, new classification criteria validated by ACR and EULAR were established. Objectives To compare the new criteria with those used so far in our hospital, as well as to assess the need for changes in the current diagnostic strategy. Methods Retrospective observational study in which 65 patients diagnosed with SS at the Hospital of Leόn were randomly included. We reviewed the diagnostic tests performed and the fulfilment of the different classification criteria developed since 1993. Other variables studied were: sex; age at the time of diagnosis and the months from the onset of symptoms; xerostomia and xerophthalmia; extraglandular involvement, ESSDAI; immunosuppression; Raynaud; lymphoma development; and analytical alterations. Results The mean age at the time of diagnosis was 54.9 years ±14 | 23–82 |, with an average of months from the onset of symptoms to the diagnosis of 10.2±9.5 | 0–36|. 90.8% were women. 87.7% presented xerostomia; and 91% showed xerophthalmia, being severe in 43.1%. 64.6% had extraglandular manifestations; being the most prevalent the joint manifestation (60%) and the cutaneous one (18.4%). Over the past year, 37% developed haematological alterations in the form of cytopenias, and 73% biological alterations. At the time of the study, 32.8% presented low activity, 38.5% moderate activity and 9.2% high activity, measured by ESSDAI; being higher in anti-Ro positive patients (p=0.011). There was no association between ESSDAI and other antibodies, Raynaud or severe ocular involvement. 10.8% required systemic immunosuppression (RTX 5, AZA 2) and 18.5% needed ocular immunosuppression (topical cyclosporine). Only one patient developed lymphoma. A Schirmer9s test (ST) was performed in 92.3% (positive in 89.2%), saving the Van Bijsterveld test for patients with severe ocular involvement. The Ocular Staining Score (OSS) was not performed in any patient. The scintigraphy of the salivary glands was positive in 70.8% of the patients and was not performed in 21.5%. The parotid sialography was only performed in two patients and the study of the salivary flow was not stimulated in none of them. Regarding the autoimmunity, 80% presented positive antiRo; 61.5% antiLa; 89% ANA; 61.5% RF; 43% quadruple positivity. Labial gland biopsy was performed only in 18.4%, with a positive result in 75%. All patients met the 1993 European Criteria; 86.2% met the European-American criteria of 2002; and only 10.8% met the SICCA-ACR Criteria. The new criteria validated by ACR and EULAR were verified in 80%. Four patients who fulfilled the European criteria did not meet the new criteria, coinciding with those patients with negative ST, but positive scintigraphy. Conclusions In our hospital, the method for electing the xerostomia study was the salivary scintigraphy; therefore, we cannot establish direct comparisons with the new criteria. The incorporation of non-stimulated salivary flow in our diagnostic strategy is necessary. We should consider conducting a lip biopsy more systematically for histological confirmation since there are no validated diagnostic criteria. Disclosure of Interest None declared

Background Sarcoidosis is a systemic granulomatous disease, being the joint involvement a poorly studied manifestation. Objectives To describe the clinical and demographic characteristics of patients with sarcoidosis, paying particular attention to the joint involvement and its possible relationship with other extra-articular manifestations, as well as the treatment recieved. Methods A retrospective, observational study that included 104 patients who were admitted to the Hospital of Leόn between January 2011 and December 2015 with main or secondary diagnosis of sarcoidosis; according to clinical onset, imaging tests and/or anatomopathological study. The variables studied were: age at the time of diagnosis, sex, type of joint involvement, forms of extra-articular involvement, serologic parameters and drugs received. Statistical analysis was performed using SPSSv22.0, p Results 57.7% of the patients included in the study were women with a mean age of 53.42±18.4 years. At the systemic level, 35% of them presented fever, 66.3% lymphadenopathy and 4.8% splenomegaly. 97.1% of the patients presented pulmonary involvement, with stage II being the most common (46.2%). Only 8 patients had cardiac abnormalities. Ocular involvement was observed in 10.6%, predominating uveitis. The most common renal manifestation was hypercalciuria in 6.7%. The presence of neurological involvement was exceptional, detecting 3 cases of neurosarcoidosis. In the cutaneous involvement (2.9%), erythema nodosum predominated (17.3%). The CRP levels were normal in 44.3% ( 30mg/dl). 62.6% presented pathological figures of ACE. The joint involvement was present in 38.5% of the patients (14.4% in the form of arthralgia, 2.9% as periarthritis, 13.5% as acute arthritis, 4.8% as chronic arthritis and 2.9% as sacroiliitis). The 19,23% debuted as Loefgren syndrome, being seen an association between the presence of acute arthritis and erythema nodosum (p0,000). The mean age observed in patients with acute arthritis was lower than the one of the other patients with other joint manifestations ( p0.044) and a statistically significant relationship was observed between the absence of joint and ocular involvement (p0,011). Regarding the treatment of joint manifestations, 30.77% of the cases were resolved with NSAIDs, 46.15% with corticosteroids in a monotherapy and 15.38% required an immunosuppressant. In our study, most patients treated with corticosteroids did not show articular nor ocular involvement (p0,018), although when analysing the ocular involvement separately, many received corticoid treatment (42.86%). Only one patient required Adalimumab for refractory uveitis and another presented anti-TNFα-induced sarcoidosis (Infliximab). Conclusions The pulmonary involvement is the predominant one in patients with sarcoidosis. The acute arthritis occurs in younger patients and is associated with the onset of erythema nodosum. The joint involvement is usually not severe and, although it has not been demonstrated, it seems that the use of corticosteroids predominates in the extra-articular manifestations. Only 1 in 4 patients showed an increase of acute phase reactants. Disclosure of Interest None declared

Background Patients with Systemic Autoimmune Diseases (SADs), in particular, systemic sclerosis, are prone to suffer from severe Raynaud9s phenomenon (RP), accompanied with digital ulcers secondary to ischemia and associated with a high rate of morbidity and mortality. Bosentan, a dual endothelin receptor antagonist, is a therapeutic option for refractory cases with an inadequate response to conventional management. Objectives The objectives of our study were: i) to assess safety and efficacy of bosentan in patients suffering from different kinds of SADs and active digital ulcers secondary to RP, ii) to determine predictive factors of response, and iii) to identify predictive factors for survival. Methods This is a retrospective observational study of patients suffering from SADs and digital ulcers secondary to RP, treated with bosentan in our department between January 1st, 2005 and December 31st, 2014. Patients with ischemic ulcers caused by other factors were excluded. The following baseline independent variables were considered: type of SAD, exposition to cold or to toxic substances, clinical and epidemiological characteristics, concomitant treatments, the coexistence of pulmonary hypertension, and number and location of digital ulcers. Therapeutic response, adverse effects, the need for amputation and death were considered as dependent outcome variables. Chi-square, Student t test, and Mann-Whitney U test were used to establish statistical significance in the univariate analysis between independent baseline variables and outcomes. A p Results We included 31 patients (26 women, mean age 57 years). Twenty patients had systemic sclerosis (10 cases the limited form, and 10 cases the diffuse form). Eight patients had concomitant pulmonary hypertension. Mean follow-up after starting bosentan was 1470 days. Six patients had, at least, an adverse effect, being the most frequent alterations of liver function tests. In 87% of the cases, ulcers improved significantly, with a clinical response within the first 12 weeks of treatment in 77% of the cases. Ninety percent of the patients received concomitant treatment with calcium channel blockers and 45% had received previous treatment with prostaglandins. Despite bosentan therapy, amputation was done in 4 patients. Type of SAD, gender, or exposition to cold did not show any significant correlation with morbidity and mortality. Nine patients died. Smoking habit showed a correlation with death (p=0.05). There was a significant correlation between the duration of the disease and death (p=0.0235), as well as with the age of the patient (p=0.0013). Pulmonary hypertension was predictive of a poor therapeutic response (p=0.043) and mortality (p=0.015). Conclusions This open study suggests that bosentan is an effective agent for ischemic digital ulcers in patients with SADs, with a favorable safety profile. Age and associated pulmonary hypertension are predictors of mortality and poor outcome. Disclosure of Interest None declared