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Background: Bisphosphonates have been reported to increase the risk of atrial fibrillation. Therefore, it is conceivable that they may increase the risk of cardioembolic ischemic stroke (IS). However, most epidemiological studies carried out thus far have not shown an increased risk of IS, though none separated by the main pathophysiologic IS subtype (cardioembolic and non-cardioembolic) which may be crucial. In this study, we tested the hypothesis that the use of oral bisphosphonates increases specifically the risk of cardioembolic IS, and explored the effect of treatment duration, as well as the potential interaction between oral bisphosphonates and calcium supplements and anticoagulants.Methods: We performed a case-control study nested in a cohort of patients aged 40–99 years, using the Spanish primary healthcare database BIFAP, over the period 2002-2015. Incident cases of IS were identified and classified as cardioembolic or non-cardioembolic. Five controls per case were randomly selected, matched for age, sex, and index date (first recording of IS) using an incidence-density sampling. The association of IS (overall and by subtype) with the use of oral bisphosphonates within the last year before index date was assessed by computing the adjusted odds ratios (AOR) and their 95% CI using a conditional logistic regression. Only initiators of oral bisphosphonates were considered.Results: A total of 13,781 incident cases of IS and 65,909 controls were included. The mean age was 74.5 (SD ± 12.4) years and 51.6% were male. Among cases, 3.15% were current users of oral bisphosphonates, while among controls they were 2.62%, yielding an AOR of 1.15 (95% CI:1.01–1.30). Of all cases, 4,568 (33.1%) were classified as cardioembolic IS (matched with 21,697 controls) and 9,213 (66.9%) as non-cardioembolic IS (matched with 44,212 controls) yielding an AOR of 1.35 (95% CI:1.10–1.66) and 1.03 (95% CI: 0.88–1.21), respectively. The association with cardioembolic IS was clearly duration-dependent (AOR≤1 year = 1.10; 95% CI:0.82–1.49; AOR>1–3 years = 1.41; 95% CI:1.01–1.97; AOR>3 years = 1.81; 95% CI:1.25–2.62; p for trend = 0.001) and completely blunted by anticoagulants, even in long-term users (AOR>1 year = 0.59; 0.30–1.16). An interaction between oral bisphosphonates and calcium supplements was suggested.Conclusion: The use of oral bisphosphonates increases specifically the odds of cardioembolic IS, in a duration-dependent manner, while leaves materially unaffected the odds of non-cardioembolic IS.

Objetivos Describir la metodología del Registro de pacientes con miopatía inflamatoria idiopática (MII) de España (Myo-Spain), así como sus fortalezas y limitaciones. El objetivo principal del proyecto es analizar la evolución y el manejo clínico de una cohorte de pacientes con MII. Material y método Estudio observacional, longitudinal, ambispectivo y multicéntrico de una cohorte de pacientes con MII atendidos en servicios de reumatología de España. Se incluirán todos los pacientes con diagnóstico de MII en seguimiento habitual por los centros participantes, sin tener en cuenta la edad de inicio del proceso. Los casos incidentes serán todos los pacientes que al inicio del estudio en cada centro estén diagnosticados desde hace menos de 12 meses y casos prevalentes desde hace más de 12 meses. Se construirá un registro en el que se incluirán los datos de la visita basal, del año y dos años. Se recogerán variables sociodemográficas, clínicas, analíticas, complicaciones, comorbilidad, asociación con otras enfermedades reumáticas, ingresos hospitalarios, mortalidad y tratamientos. Además, se determinarán índices, escalas y cuestionarios de actividad, afectación muscular, daño, discapacidad y calidad de vida. El periodo de reclutamiento será de 23 meses. El propósito es conseguir una cohorte de 400 pacientes con MII. Conclusiones El estudio Myo-Spain constituye la oportunidad para desarrollar una cohorte de pacientes incidentes y prevalentes con MII en España. Myo-Spain permitirá evaluar en detalle, las características clínicas de la enfermedad en diferentes momentos. Se espera que la información exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros análisis. Objectives: To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Methods: Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Conclusions: Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis. Sin financiación No data JCR 2021 0.311 SJR (2021) Q3, 44/61 Rheumatology No data IDR 2021 UEM

Rheumatic diseases are extensively managed with biological disease-modifying antirheumatic drugs (bDMARDs), but a notable proportion of patients withdraw in the long term because of lack of effectiveness, adverse events, or the patient's decision. The present real-world analysis showed the effectiveness, retention, and safety data collected in the Spanish BIOBADASER registry for patients with psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA, including ankylosing spondylitis (AS) and non-radiographic axSpA) treated with secukinumab, a human antibody against interleukin-17A (IL-17A), for more than 12 months. Six hundred and thirty-nine patients were analysed (350, 262, and 27 PsA, AS, and nr-axSpA patients, respectively). The results showed an improvement in the disease activity after 1 year of treatment, in terms of decreases of the mean Disease Activity Score 28 using C-reactive protein (DAS28-CRP), the mean Disease Activity Psoriatic Arthritis (DAPSA) score, swollen joint counts (SJC), and tender joint counts (TJC) in PsA patients and decreases in the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the mean Ankylosing Spondylitis Disease Activity Score (ASDAS) in axSpA patients. This improvement was maintained or increased after 2 and 3 years of treatment, indicating that secukinumab is effective in both naïve and non-responder patients. Retention rates were higher when secukinumab was used as the first-line biological treatment, although they were also adequate in the second and third lines of treatment. Collected safety data were consistent with previous reports.

Objectives To describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM. Methods Observational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM. Conclusions Myo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.

Background Oral and/or genital aphthous ulcers are the most common symptoms of Behçet´s disease (BD), and are often refractory to conventional treatment. The inhibitor of phosphodiesterase-4 apremilast (APR) has demonstrated efficacy in the treatment of this manifestations. The objective of the present study was to assess the efficacy of APR in the management of refractory oral and/or genital ulcers in patients with BD. Methods National multicenter open-label observational study on BD patients with recurrent oral and/or genital ulcers. In all cases orogenital ulcers were refractory to conventional therapy. APR was given and maintained at standard dose of 30 mg twice daily. The main outcome was the achievement of oral and/or genital ulcers remission. Efficacy of APR for other clinical manifestations was also evaluated. Results We included 51 patients (35 women/16 men; mean age 44.7 ± 13.2 years). Before APR, all patients had received several systemic conventional and/or biologic drugs. APR was initiated because of refractory oral (n = 19) or genital (n = 2) aphthous ulcers or both (n = 30). Other manifestations found at APR onset were arthralgia/arthritis (n = 16), folliculitis/pseudofolliculitis (n = 14), erythema nodosum (n = 3), furunculosis (n = 2), paradoxical psoriasis induced by TNFα-inhibitors (n = 2), ileitis (n = 2), deep venous thrombosis (n = 2), leg ulcers (n = 1), erythematosus and scaly skin lesions (n = 1), fever (n = 1), unilateral anterior uveitis (n = 1) and neurobehçet (n = 1). After a mean follow-up of 8.5 ± 6.9 months, most patients had experienced improvement of orogenital ulcers and prednisone dose had been successfully reduced or discontinued. APR also yielded improvement of some non-aphthous manifestations such as the cutaneous follicular and intestinal manifestations. However, the effect on musculoskeletal manifestations was variable. Conclusion APR yielded a rapid and maintained improvement of refractory mucocutaneous ulcers of BD, even in patients refractory to several systemic drugs including biologic therapy.

Background: In inflammatory diseases, such as rheumatoid arthritis, early treatment has demonstrated to improve disease control and decrease mortality. It is not known if an early treatment could have similar effects on inflammatory myositis (IM) patients. Objectives: To analyze if the delay between initial symptoms and diagnosis or therapy initiation influences disease control or mortality in IM patients. Methods: All patients from REMICAM were included (1). The influence of time elapsed between initial symptoms and diagnosis or start of therapy, and the year of diagnosis (before or after 2000), on mortality and disease control (defined as the possibility of glucocorticoid (GC) withdrawal due to IM improvement), was studied by means of survival analysis and regression proportional hazard bi and multivariate Cox models. All factors with p Results: From 479 patients (74% females, 52% polimiositis, 44±22 years at diagnosis, 10±8 years follow up), 208 (43%) were diagnosed before 2000, and 473 (99%) received any treatment: 473 (99%) oral GC, 50/344 (15%) GC pulses, 78 (16%) HCL, 355 (74%) immunosuppressants (IS) (MTX 228, LF 10, AZA 190, CYP 44, MP 38, CyS 32), 55 (12%) biologics (RTX 45, abatacept 2, aTNF 16) and 79 (17%) IVIG. Disease control was more frequent in younger patients, diagnosed after year 2000, and was independently associated with less ILD presence, lower n° of therapies and a shorter time between the initial symptoms and the start of IS therapy (Table 1). Risk factors for mortality were age, male sex and cancer, but not the delay in diagnosis or in the start of therapy (Table 2) Conclusion: In the REMICAM cohort, disease control is more frequent in younger patients, diagnosed after 2000, with early initiation of IS therapy. Mortality was not associated with the delay in diagnosis or therapy in our study. Our data support the hypothesis that, in IM, as in other inflammatory diseases, an early treatment is essential to decrease inflammation and achieve disease control. Reference: [1] Nuno L, Rheumatol Clin 2017; 13:331-337 Disclosure of Interests: Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Laura Nuno: None declared, Francisco J Lopez-Longo: None declared, Julia Martinez-Barrio: None declared, Carmen Larena: None declared, Valentina Maldonado : None declared, Carmen Barbadillo: None declared, Paloma Garcia de la Pena: None declared, Irene Llorente : None declared, Eva Tomero Muriel: None declared, Ana Perez Gomez: None declared, Henry Moruno : None declared, Tatiana Cobo-Ibanez: None declared, RAQUEL ALMODOVAR: None declared, LETICIA LOJO : None declared, Maria Jesus Garcia de Yebenes: None declared, Patricia Carreira: None declared

Background Secukinumab, an inhibitor of IL-17, is a new option for the treatment of Psoriatic Arthritis (PsA) which has showed efficacy in clinical trials. However, real-world data of its use is still scarce. Objectives This study aims to analyze the experience of using secukinumab for PsA in four tertiary hospitals. Methods Multicentric observational, longitudinal, retrospective study conducted in 4 tertiary hospitals of the Madrid region. Patients with clinical diagnosis of PsA and having received at least one dose of secukinumab were included. Medical records were reviewed to collect demographic and clinical data (body mass index, BMI, risk factors cardiovascular disease, cancer, HBV/HCV infection), features of PsA (extra-articular involvement, radiological damage), previous therapies, assessment of the disease and response data at 6 months of secukinumab (joint counts, CRP, DAPSA, reasons for discontinuation, adverse events). Descriptive statistic analysis using mean and standard deviation was performed. Results 177 patients, of which 115 female (65%) were included. Mean age was 53 y.o.(SD 15) and average duration of the disease was 9 years (SD 7). 169 patients (95%) had peripheral disease (34% joint erosions), 84 (47%) had axial disease (68 with radiological damage), 148 (84%) had psoriasis, 61 (34%) showed dactilitis and 111 (63%) had enthesitis. Average BMI was 28.4 (SD 6), with an obesity rate of 37% (52 pt). Observed comorbidities were hypertension (22 pt, 12%), diabetes mellitus (22 pt, 12%), dyslipidemia (58 pt, 33%), active smoking (55 pt, 31%) and others: 20 patients had HBV infection, 5 had HCV infection and 12% had malignancy. Regarding previous treatments, 90% had received cDMARDs, particularly methotrexate (77%) and 119 (67%) had been exposed to at least one bDMARD (32% to one, 25% to two, 20% to three and 21% to four or more). 69% were on 150 mg dose and 31% on 300 mg dose. At baseline, average tender joint count was 7 (SD 8), swollen joint count was 4 (SD 4), CRP 7 mg/l and DAPSA 26. At 6 months of secukinumab therapy, tender joint count had decreased to 5 (SD 8), swollen joint count 2 (SD 3), CRP 5 mg/l and DAPSA 17. Thirty-eight (47%) of the patients with the data available (80) had DAPSA ≤14 (low activity) and 9 DAPSA ≤4 (remission). In naive to biologic patients, DAPSA varied from 27 in the baseline visit to 16 at 6 months, and in the other group of patients with biologic experience, DAPSA varied from 24 to 17 at 6 months (if they had been exposed to 3 or more biologics, DAPSA from 18 to 10 at 6 months). Average drug survival time was 20 months (1-34). 79 patients (44.6%) withdrawn therapy, due to primary ineffectiveness (40), secondary ineffectiveness (26), adverse events (9) and other reasons (3). Adverse events do not differ from those reported in clinical trials. Conclusion Secukinumab in real-world setting had been indicated in a population of PsA with a high percentage of axial involvement (47%), with an important previous exposure to biologics, and with higher comorbidity than that reported in clinical trials. Response data were favorable, 47% of patients achieved remission or low activity by DAPSA, and similar profile of adverse events to the one reported in the clinical trials was observed. References [1] Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. for the FUTURE 1 Study Group* Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med2015;373:1329-39 Disclosure of Interests MARIA MARTIN LOPEZ: None declared, Marta Valero: None declared, Valentina Emperiale: None declared, Carolina Merino Argumanez: None declared, Javier Bachiller-Corral: None declared, Jose Campos Esteban: None declared, Ana Perez Gomez: None declared, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen

Background: Systemic Sclerosis is a multisystem autoimmune disease characterized by fibrosis of the skin and internal organs and vascular damage. The diagnosis is usually made in the late stages, when irreversible damage has already occured. Recently, we have established new criteria to detect early cases of the disease. Performing capillaroscopy and its findings are crucial in the diagnosis of early systemic Sclerosis or “prescleroderma” and there may be changes seen in capillaries of patients without skin manifestations. Objectives: To analyze the nailfold capillaroscopy findings in patients with anti-centromere or anti-topoisomerase antibodies and evaluate their usefulness for the diagnosis of systemic sclerosis. Methods: Of a total of 255 capillaroscopy performed in our Rheumatology department, those patients with positive anti-centromere or anti-topoisomerase were selected. In all cases, capillaroscopy was performed in eight fingers, always by the same observer. The following findings were considered pathological or scleroderma pattern: Local or global capillary loss (> 20%), hemorrhages: two or more in at least two fingers and enlarged capillaries: two or more capillary with double or more caliber in at least two different fingers. Statistical analysis was performed with SPSS 19.0 program. Results: The study included 69 patients: 5 (7.2%) males and 64 (92.8%) women, 14 (20.3%) smokers, 47 (68.1%) non-smokers and 8 (11.6%) quitters. The characteristics of the patients included in the study were as follows: 20 patients (30%) were previously diagnosed of systemic sclerosis (19 limited and one diffuse), of which 4 patients had concomitant primary biliary cirrhosis Syndrome (Reynolds), 1 patient with primary biliary cirrhosis and positive anti-centomere without the presence of Raynaud, one patient diagnosed with Sjogren’s syndrome with positive anti-centromere without presence of Raynaud, 26 patients with suspected early systemic sclerosis and 21 patients with disease-specific autoantibodies in the absence of Raynaud. Nailfold capillaroscopy was normal in 32 patients (46.4%) and pathological (scleroderma pattern) in 37 patients (53.6%); we detected limited enlarged capillaries in 26.2%, generalized enlarged capillaries also in 26.2%, giant capillaries in 37.7%, local loss of capillaries in 27.9%, global loss of capillaries in 8.2%, hemorragies in small claims in 29.5% and abundant hemorrhagies in 9.8%. All patients previously diagnosed of systemic sclerosis had a pathological capillaroscopy except one. However, no changes were observed in capillaroscopy in patients who had only disease-specific autoantibodies in the absence of Raynaud’s phenomenon. While, the 26 patients who were referred for suspected systemic sclerosis (at least with the presence of Raynaud and autoantibodies) in 18 (69.9%) of these scleroderma pattern was observed with subsequent diagnosis of early systemic sclerosis or “prescleroderma”. Conclusion: Nailfod capillaroscopy is a useful and inexpensive tool for the diagnosis of systemic sclerosis. The scleroderma pattern is very specific of this disease and we can make an early diagnosis even in patients who only have autoantibodies and Raynaud’s phenomenon, without the presence of other severe manifestations. We have also observed that the absence of Raynaud’s phenomenon is associated with a normal result on capillaroscopy. Reference [1] Nailfold digital capillaroscopic findings in patients with diffuse and limited cutaneous systemic sclerosis. Saeedeh Shenavandeh, Mahyar Yousefipour Haghighi, Mohammad Ali Nazarinia. Reumatologia 2017; 55, 1: 15–23 Disclosure of Interests: None declared

Background Inflammatory myositis (IM) are heterogeneous autoimmune diseases, characterized by muscular inflammation, which can associate systemic manifestations. In other inflammatory diseases, as rheumatoid arthritis, inflammation is a cardiovascular risk factor (CVRF), with clear influence on cardiovascular events and mortality (CVE, CVM). Objectives To analyze the influence of IM severity in the development of CVE and CVM in the REMICAM registry. Methods All patients from REMICAM were included(1). REMICAM is a retrospective multicentric registry of IM patients (n=479), performed in Madrid between 2012 and 2014, containing demographic, clinical and outcome data (1). The presence of extra muscular features (cardiac, pulmonary, cutaneous and systemic involvement), number of therapies, immunosuppressants (IS) need, and glucocorticoids (GC) withdrawal due to IM remission defined IM severity. Bi and multivariate logistic regression analysis were used to determine the association between these factors and CVE. Survival analysis and regression proportional hazard bi and multivariate Cox models were used to determine the effect of these factors on CVM. All factors with p Results From 479 patients (74% females, 52% polymyositis, 44±22 years at diagnosis, 10±8 years follow up), 104/467 (22%) presented CVE and 24/409 (6%) died due to CVE. CVE were associated to age, male sex, CVRF number, diagnosis before year 2000, presence of arrhythmia or Raynaud (Table 1). Arrhythmia was the only independent risk factor for CVM. GC withdrawal due to IM remission, and a smaller number of therapies, were protective factors for CVM (Table 2). Conclusion In the REMICAM registry, extra muscular manifestations such as arrhythmia, were associated to CVE and CVM, as independent risk factors. A smaller number of treatment or GC withdrawal due to remission were protective factors for CVM. Our results support the hypothesis that more severe IM, with extra muscular involvement and persistent inflammation, could favor atherosclerosis and CVE development. Reference [1] Nuno L, Rheumatol Clin2017; 13:331-337 Disclosure of Interests Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Laura Nuno: None declared, Francisco J Lopez-Longo: None declared, Julia Martinez-Barrio: None declared, Carmen Larena: None declared, Valentina Maldonado : None declared, Carmen Barbadillo: None declared, Paloma Garcia de la Pena: None declared, Irene Llorente : None declared, Eva Tomero Muriel: None declared, Ana Perez Gomez: None declared, Henry Moruno : None declared, Tatiana Cobo-Ibanez: None declared, RAQUEL ALMODOVAR: None declared, LETICIA LOJO : None declared, Maria Jesus Garcia de Yebenes: None declared, Patricia Carreira: None declared

Background Secukinumab is a newly introduced biologic therapy against IL-17 which has been approved for Psoriatic arthritis and has showed efficacy in clinical trials, but real world data is still lacking. Objectives This study aims to analize secukinumab drug survival for psoriatic arthritis in a real world environment. Methods Multicentric observational, longitudinal retrospective study conducted at 4 tertiary hospitals in Madrid region. Patients with clinical diagnosis of psoriatic arthritis which had received at least one dose of secukinumab between january 2016 and october 2018 were included. With follow up period till December 31, 2018. Medical records were reviewed to collect data about psoriatic arthritis involvement, comorbidities, previos DMARD and bDMARD therapies and its reasons for discontinuation, duration of secukinumab therapy, reasons for discontinuating secukinumab therapy and adverse events. Statistical analysis was performed including bivariate analisys (considering withdrawal of drug during study period or not) and survival analysis with Kaplan-Meier and Cox regression. Results 177 patients that initiated secukinumab therapy in the recruitment period were included. 123 pacients were on 150 mg dose and 54 on 300 mg dose. Average follow up period was 13 months (SD 8,28; range 1-34) in the bivariate analysis, a higher proportion of biologic-naive patients was found among the group without secukinumab withdrawal during the study (40% vs 23%, p 0.07). No other differences were observed between both groups regarding demographic characteristics nor comorbidities (tobacco exposure, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease or malignancy). Median survival time for secukinumab in the Kaplan-Meier analysis was 21.2 months (IC 95%: 14.3 - 22.2), with an average of 19,9 months. One event was censored due to lost to follow-up. Secukinumab treatment was withdrawn in 79 patients (44.6%). Reasons for discontinuation were lack of effectiveness (37%), either primary (40 patients) or secondary (26 patients), adverse events (9 patients, 0,5%), elective surgery in one patient and latex allergy in other. The only variable associated to higher drug survival in Cox regression analysis was biologic-naive status. No differences in drug survival were found in all other variables studied (gender, age, secukinumab dosage, illness duration, clinical features, tobacco exposure and rest of comorbidities). Conclusion As secukinumab was marketed in 2016, real-word setting studies lack long term data. The mean follow up period in our study was 13 months. Most of withdrawals were to lack of effectiveness. Median survival was 21.2 months, significatively higher in biologic-naive patients. No other differences were found in all other variables studied. Probably real-world data differ from those of clinical trials. Disclosure of interests Marta Valero: None declared, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, abbVie, and Janssen, Maria Martin: None declared, Jose Campos Esteban: None declared, Carolina Merino argumanez: None declared, Valentina Emperiale: None declared, ana Perez Gomez: None declared, Javier Bachiller-Corral: None declared

Background Although glucocorticoids (GC) remain the cornerstone in the treatment of inflammatory myositis (IM), the management of these processes is not yet standardized. Experts recommend early use of immunosuppressants (IS), in order to prevent GC side effects. It is not known what is the actual management in clinical practice. Objectives To describe the management of IM in REMICAM registry, and to identify differences according to disease subtype (polymyositis (PM), or dermatomyositis (DM)), and to the year of diagnosis (before or after 2000). Methods All patients from REMICAM were included (1). A descriptive analysis of the different therapies (GC, IS, biologics, IV immunoglobulins (IVIG), and hydroxychloroquine HCL) was performed, attending to possible differences between IM subtype and the year of diagnosis. T student and Chi square tests were used for quantitative and qualitative variables, respectively. Results From 479 patients (74% females, 52% PM, 44±22 y at diagnosis, 10±8 y follow up), 473 (99%) received oral GC, 50/344 (15%) pulses GC, 78 (16%) HCL, 355 (74%) IS (methotrexate MTX 228, leflunomide 10, azathioprine AZA190, cyclophosphamide 44, mycophenolate MP 38, cyclosporine 32), 55 (12%) biologics (rituximab 45, abatacept 2, aTNF 16) and 79 (17%) IVIG. Differences according to IM subtype (1), and to the year of diagnosis (2), are shown in Tables. Conclusion The therapeutic management of IM has changed over the last few years, with a clear increase and earlier use of IS in patients diagnosed after 2000. In spite of a more aggressive approach in recent years, severe infections are less frequent, perhaps as a consequence of lower GC doses. The management of PM and DM is similar. Reference [1] Nuno L, Rheumatol Clin2017; 13:331-337 Disclosure of Interests Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, AbbVie, and Janssen, Laura Nuno: None declared, Francisco J Lopez-Longo: None declared, Julia Martinez-Barrio: None declared, Carmen Larena: None declared, Valentina Maldonado : None declared, Carmen Barbadillo: None declared, Paloma Garcia de la Pena: None declared, Irene Llorente : None declared, Eva Tomero Muriel: None declared, Ana Perez Gomez: None declared, Henry Moruno : None declared, Tatiana Cobo-Ibanez: None declared, RAQUEL ALMODOVAR: None declared, LETICIA LOJO : None declared, Maria Jesus Garcia de Yebenes: None declared, Patricia Carreira: None declared

Background: Oral and/or genital aphthous ulcers are the most common symptoms of Behcet’s disease (BD), and are often refractory to conventional treatment. The inhibitor of phosphodiesterase-4 Apremilast (APR) has demonstrated efficacy in the treatment of this manifestations. Objectives: To assess the efficacy and safety of APR in BD patients with oral and/or genital ulcers refractory to conventional treatment. Methods: National multicenter open-label study on 49 BD patients treated with APR at maintained standard dose of 30 mg twice daily, with the initial 5-day titration schedule in 38 cases. The main outcome was achievement of oral and/or genital ulcers remission. Results: We included 49 patients (35 women/14 men), mean age of 44.5±13.4 years. Before APR, all patients had received several systemic conventional and/or biological drugs: oral corticosteroids (n=45), colchicine (n=48), NSAIDs (n=21), methotrexate (n=27), azathioprine (n=23), cyclosporine (n=9), dapsone (n=6), adalimumab (n=12), infliximab (n=8), tocilizumab (n=3), etanercept (n=3), sulfasalazine (n=2), cyclophosphamide (n=2) and/or others (pentoxifylline, thalidomide, mycophenolate mofetil, hydroxychloroquine, golimumab, 1 each). The main clinical symptoms for starting APR were oral (n=18) and genital (n=2) aphthous ulcers or both (n=29). After a mean follow-up of 8.3±6.8 months, most of the patients experienced main clinical improvement and prednisone dose was reduced or discontinued (TABLE). In this period of time, 31 patients developed any side-effect, most of them transitory: nausea (n=12), diarrhea (n=11), dyspepsia (n=9), abdominal pain (n=7), headache (n=5), loss of appetite (n=4), weight loss (n=3), halitosis (n=1), dry mouth (n=1), palpitations (n=1) and/or depression (n=1). Six patients had to reduce the dose to 30 mg/day. APR was discontinued in 11 patients due to: not obtaining the expected improvement (n=5), intense gastrointestinal adverse effects (n=3), desire of pregnancy (n=1), persistent erythema nodosum (n=1) and development of neurological involvement (n=1). Conclusion: Our data show a rapid and maintained improvement with APR in patients with mucocutaneous ulcers of BD refractory to several systemic drugs, including biologic therapy. References: [1] Davatchi F, et al. The International Criteria for Behcet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatology Venereol. 2014;28(3):338–47. [2] Gulen Hatemi, et al. Apremilast for Behcet’s Syndrome — A Phase 2, Placebo-Controlled Study. N Engl J Med 2015; 372:1510-1518. Disclosure of Interests: Belen Atienza-Mateo: None declared, Jose Luis Martin-Varillas: None declared, J. Loricera: None declared, Vanesa Calvo-Rio: None declared, Jenaro Grana: None declared, Gerard Espinosa: None declared, Clara Moriano: None declared, Trinidad Perez-Sandoval: None declared, Manuel Martin-Martinez: None declared, Elvira Diez Alvarez: None declared, Maria Dolores Garcia-Armario: None declared, Esperanza Martinez: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Patricia Moya: None declared, Francisca Sivera: None declared, Jaime Calvo Consultant for: Bristol-Myers Squibb, Janssen, Celgene, Sanofi Genzyme, Speakers bureau: Bristol-Myers Squibb, Isabel de la Morena Speakers bureau: Abbvie, Celgene, Pfzier, UCB, Ghebro, Roche, Sanofi, Janssen., Francisco Ortiz-Sanjuan: None declared, Jose Andres Roman-Ivorra: None declared, Ana Perez Gomez: None declared, Sergi Heredia: None declared, Alejandro Olive: None declared, Agueda Prior-Espanol: None declared, Carolina Diez: None declared, Juanjo J Alegre-Sancho: None declared, D Ybanez-Garcia: None declared, Angels Martinez-Ferrer: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Ignasi Figueras: None declared, Ana Isabel Turrion : None declared, Susana Romero-Yuste: None declared, Pilar Trenor: None declared, Soledad Ojeda Grant/research support from: AMGEN, Speakers bureau: AMGEN, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Monica Calderon-Goercke: None declared, D. Prieto-Pena: None declared, Inigo Gonzalez-Mazon: None declared, Lara Sanchez Bilbao: None declared, Miguel A. Gonzalez-Gay: None declared, Ricardo Blanco: None declared

Background Pathophysiology of primary Sjogren syndrome (SSp) is characterized by oligoclonal B-cell proliferation and ectopic lymphoid tissue formation. The association between ultrasound glandular parenchyma heterogeneity and hyperproduction of autoantibodies, which in turn represents characteristic B-cell hyperactivity of SSp, is described. Objectives To study the association between major salivary gland ultrasound (MSGUS) and their respective pathological grades with the analytical and serological data, and activity indexes obtained in patients with suspected SSp. Methods 72 patients were recruited consecutively with clinical and/or analytical suspicion of SSp from the Rheumatology outpatient consultations at the Principe de Asturias Hospital (2015-2018). Demographic, serological and validated activity indexes, ESSPRI and ESDAI, were collected. All of them underwent a MSGUS and their results were classified in three grades according to the Cornec et al system: normal (grade 0 and 1), mild (grade 2) and moderate-severe (grades 3 and 4). The final SSp diagnosis was made using both 2002 AECG and 2016 ACR/EULAR classification criteria. Data were analyzed using the software STATA. Association between MSGUS and qualitative variables was described according to the number of cases and the percentage by grades of MSGUS; the significance of the associations was tested with the Chi square test. As for the quantitative variables, the association was described with median and interval interquartile (IIQ) by grades of MSGUS and the significance of the association was verified with the non-parametric test of Kruskall-Wallis. Results From patients with pathological MSGUS: 51% had antiRo52, 51% antiRo60 and 36% anti-La positive; 62% hypergammaglobulinemia, 40% positive rheumatoid factor (RF), 6% and 13% C3 and C4 hypocomplementemia, respectively. Mean values were obtained: ESR 36, CRP 1.6, RF 12, ESSPRI 5.6 and ESSDAI 2. Statistically significant differences (p 0.150 in all associations explored). No differences have been found for RF, C3 and C4 hypocomplementemia, ESR, CRP and ESSDAI variables (table1). Conclusion In this series of patients, a statistically significant association was found between the positivity of anti-Ro antibodies, hypergammaglobulinemia and MSGUS, as well as its subdivision by pathological grades. No statistical significant association was found between MSGUS and positivity of antiRo60 and antiLa antibodies and ESSPRI, probably due to the small sample size. There were no differences for the rest of the variables analyzed (RF, complement, acute phase reactants and ESSDAI). References [1] Ultrasonography of salivary glands-a highly specific imaging procedure for diagnosis of Sjogren’s syndrome Dirk Wernicke J Rheumatol. 2008Feb;35(2):285-93. Epub 2008 Jan 15 [2] .The usefulness of ultrasound in the diagnostics of Sjogren’s syndrome. Fadhil Saied J Ultrason. 2013 Jun;13(53):202-11. Disclosure of Interests None declared

Background IL-17 inhibition has been proved effective in patients with ankylosing spondylitis (AS) in clinical trials and it has been added to the most recent national and international treatment guidelines. However, real-world data of its use is still scarce. Objectives This study aims to describe the axial spondyloartrhtitis (AxSpA) population receiving secukinumab therapy under non-experimental conditions. Methods Multicentric observational, retrospective, longitudinal study conducted in 4 tertiary hospitals of the Madrid region. Patients over 18 y.o. With clinical diagnosis of axSpa and having received at least one dose of secukinumab were included. Medical records were reviewed to collect demographic and clinical data related to axSpA, its features and treatment. Descriptive statstic analysis with measures of central tendency and measures of variability was performed. Results 143 patients, of which 68 women (47.6%) were included. Mean age was 50.6 y.o.(26-74) and average duration of the disease was 12.4 years (1-54). 105 aS patients (73.4%) and 38 non radiographic axSpA patients (26.6%). 85 of them were HLAB27 positive (62%) Observed comorbidities were hypertension (37pt, 25.8%), diabetes mellitus (12pt, 8.4%), dyslipidemia (43 pt,30.1%) and active smoking (41pt,28.7%) average BMI was 27.1 (15.8-43.4), with an obesity rate of 27.6% (29pt). Other comorbidities highlighted were ischemic heart disease (10pt, 7%), HBV infection (10pt, 7.5%), malignancy (14pt, 9.8%) and renal transplantation (2 pt, 1.4%). No HVC nor HIV infections were detected. In terms of axial disease, 97 (65.7%) patients showed grade 2 or higher sacroilitis. In sacroiliac joint MRI studies 35 patients (42.7%) had acute and chronic lesions, 13 (15.9%) had acute lesions, 17 (20.7%) had chronic lesions and 17 (20.7%) were normal. Syndesmophytes were present in 49 patients (34.5%) and hip arthropathy in 15 patients (11.4%). In addition, peripheral disease was present: 77 patients (53.8%) had arthritis, 80 patients (55.9%) had enthesitis and 9 patients (6.3%) showed dactilitis. Joint erosions in hand and feet X-rays were reported in 6 patients (6.8%). Extraarticular SpA features found were inflammatory bowel disease in 3 patients (2.1%), uveitis in 17 pts (11.9%) and psoriasis in12 pts (8.4%). 2 patients (1.4%) presented secondary amiloidosis. Regarding previous treatments, 97.2% had used NSAIDs and 38.5% glucocorticoids. 100 patients (84.1%) had received DMARDs, particularly sulfasalazine (84 pts, 58.7%). 38 patients were naive to biologic therapy (26.6%); 36 (34.3%) had been exposed to one bDMARD, 39 (37.1%) to two and 30 (28.6%) to three or more. Besides all TNF inhibitors, 13 treatments with abatacept, tocilizumab, rituximab or ustekinumab were recorded. Average baseline BASDAI was 6.54 (0.4-12.8), and 5.01 (0-10) after 6 mo SCK therapy. Baseline BASFI was 5.8 (0.4-10) and 4.8 (0-9.6) at 6 months. Adverse events did not differ from those reported in clinical trials. Conclusion Population receiving SCK in real-world setting is different to clinical trials: more complex patientes, with higher disease activity, higher use of previous bDMARDs and higher comorbidity, particularly cardiovascular risk, infections or malignancy that could preclude the use of other biologic therapies. A relevant percentage of off-label prescription in nrAxSpA is reported. Further studys are needed to characterize this population and its clinical response and tolerability to SCK therapy. Disclosure of interests Valentina Emperiale: None declared, Jose Campos Esteban: None declared, Carolina Merino argumanez: None declared, Javier Bachiller-Corral: None declared, Marta Valero: None declared, Beatriz Joven-Ibanez Speakers bureau: Celgene, Novartis, MSD, Pfizer, abbVie, and Janssen, Maria Martin: None declared, ana Perez Gomez: None declared

Background: Nailfold capillaroscopy (CP) is a simple, safe, low cost and non-invasive screenig test and together with the study of autoantibodies, is useful in the diagnosis of systemic sclerosis (SSc). It demonstrates certain specific patterns which are characterized by the presence of dilated capillaries, haemorrhages and avascular areas. Other systemic autoimmune diseases (SAD) do not have a specific pattern, but certain alterations in the morphology of the capillaries such as increased tortuosity have been described in SLE. In other diseases such as mixed connective tissue disease (MCTD), inflammatory myopathies and overlap syndromes, findings may be different to the pathological findings consistent with scleroderma pattern. Objectives: Description of nailfold capillaroscopic findings in different SAD. Methods: The study included 255 patients referred for CP that was performed in 8 fingers, and always by the same observer. The following findings were considered as “scleroderma pattern”: Local or global capillary loss (> 20%), haemorrhages: two or more in at least two fingers and enlarged capillaries: two or more capillary with double caliber or more in at least two different fingers. Abundant evidence of tortuosity (> 20%) as ringlets tangles and no evidence of disorders described above, was considered nonspecific, tortuous pattern or suspects SAD. Statistical analysis was performed with SPSS 19.0 program. Results: CP was performed in 255 patients, 31 males (12%) and 224 (88%) women. 23 patients (9%) had a diagnosis of SSc, 6 patients (2%) of SLE, other 6 (2%) of Sjogren’s syndrome, 7 (3%) of MCTD, 4 (1.5%) of inflammatory myopathy and 2 (0.8%) of overlap syndrome. 18 patients (7%) had positive aNA and Raynaud without another data suggestive of SAD, 76 patinents with primary Raynaud (30%) and 66 patients (26%) with a miscellany of other diseases such as antiphospholipid syndrome, vasculitis, fibromyalgia and psoriatic arthritis. Also, 29 patients (12.4%) were sent for performing CP for suspected systemic sclerosis and 16 patients (6.3%) presented with only positive anti-centromere. CP was normal in 191 patients, while in 45 patients scleroderma pattern was observed and in 19 patients nonspecific pattern suggestive of SAD was seen. Capillaroscopic findings: in each of the 23 patients diagnosed with SSc, 21 patients had scleroderma pattern. Of the 6 patients with SLE, CP was normal in 4 patients, while one patient had abundant tortuosity. Likewise, the 6 patients with Sjogren’s syndrome, only one patient had a nonspecific pattern suggestive of SAD. Of the 7 patients with MCTD, four had normal CP, two had a scleroderma pattern and one had tortuous pattern. The 2 patients with overlap (myopathy-scleroderma and Lupus-scleroderma) both had a pathological CP with scleroderma pattern. Conclusion: Our study demonstrates that the evidence of scleroderma pattern is very specific of SSc. However, in certain diseases such as MCTD, overlap syndromes and inflammatory myopathies, we can also see this pattern. In other SAD, CP is usually normal or may show some nonspecific changes. References: The contribution of capillaroscopy to the differential diagnosis of connective autoimmune diseases. Best Practice & Research Clinical Rheumatology Vol. 21, No. 6, pp. 1093–1108, 2007 Disclosure of interests: None declared

Background Minor salivary gland biopsy (MSGB) is the gold-standard technique for primary Sjogren Syndrome (SSp) but nowadays the use of mayor salivary gland ultrasonography (MSGUS) is increasing because it is a fast and non-invasive technique and with no adverse events for the patient. Objectives To assess the utility of MSGUS as a diagnostic tool for SSp and to study the concordance with MSGB. Methods 72 patients were recruited consecutively with clinical and/or analytical suspicion of SSp, from the Rheumatology outpatient consultations at the Principe de Asturias Hospital (2015-2018). Demographics, clinical and serological data and validated activity indexes, ESSPRI and ESSDAI, were recorded. All patients underwent a MSGB and blindly, both for clinical and histological results, a MSGUS. The histological results were classified according to Chisholm and Mason scores (pathological grades 3/4), and the US results according to the system by Cornec et al. (pathological grade ≥2). The final SSp diagnosis was made using both the 2002 and the 2016 ACR/EULAR classification criteria. The data was analyzed using the software STATA. The validity of the US and the MSGB to diagnose SSp according to the 2002 and 2016 ACR/EULAR classification criteria was evaluated by calculating the percentage of agreement between the tests, along with the specificity (Sp), sensitivity (S), positive and negative predictive values (PPV and NPV) and area under the curve (AUC). Results Descriptive analysis of the main variables is shown in Table 1. Using the MSGB as a gold-standard, the total% of agreement was 78% with a good AUC (0.75) (IC95%0.65-0.84). Using the 2002 classification criteria as a gold-standard, the total% of agreement was 82% for US and 79% for MSGB with an AUC of 0.78 (IC95%0.67-0.88) and 0.80 (IC95%0.70-0.89) respectively. In this case, US had a S of 93% (IC95%0.82-0.99) and a Sp of 62% (IC95%0.41-0.80) whereas MSGB had a S of 78% (IC95%0.64-0.89) and a Sp of 81% (IC95%0.61-0.93). Similar results were obtained using ACR/EULAR criteria: US% of agreement 83%, AUC 0.78 (IC95%0.67-0.90), S 90% (IC95%0.79-0.97) and Sp 67% (IC95%0.43-0.85); while MSGB% agreement 81%, AUC 0.83 (IC95%0.75-0.92), S 76% (IC95%0.63-0.87) and Sp 90% (IC95%0.70-0.99). In addition, 9 patients who fullfilled the 2002 classification criteria with a negative histological result had a pathological US. Conclusion MSGUS has a similar diagnostic value compared to MSGB in patients with SSp, which could be part of the classification criteria used to date. In this series of patients and compared to MSGB, it has a higher sensitivity and a lower specificity, so it could be used as an initial diagnostic method in patients with high suspicion of disease, leaving the MSGB for those cases in which US and other clinical and serological data are inconclusive. With this approach, the disadvantages derived from an invasive technique such as MSGB would be avoided. References [1] Zhou M. Diagnostic accuracy of salivary gland ultrasonography with different scoring systems in Sjogren’s syndrome: a systematic review and meta-analysis. Sci Rep. 2018 Nov 20;8(1):17128. [2] Ultrasonography of major salivary glands compared with parotid and labial gland biopsy and classification criteria in patients with clinically suspected primary Sjogren’s syndrome Esther MosselMossel E, et al. Ann Rheum Dis 2017. Disclosure of Interests None declared

espanolEl aula invertida es un modelo de ensenanza-aprendizaje en el que los alumnos tienen el primer contacto con la informacion a ser aprendida fuera de clase, mediante documentos (textos y videos) que el docente les hace llegar por medios electronicos. El tiempo de clase asi ahorrado se dedica a actividades de aula que consolidan la asimilacion de ese conocimiento y lo aplican a la resolucion de cuestiones, casos y problemas. Este modelo de aprendizaje reduce el tiempo de instruccion directa en clase y aumenta el dedicado al aprendizaje activo. Se transfi ere al alumno la responsabilidad de esforzarse inicialmente para alcanzar un nivel de comprension basico y comunicar sus difi cultades y dudas al docente. Asi, el docente recibe informacion sobre cuales son las difi cultades y necesidades de sus alumnos y podra adaptar las activida-des que realizara en el aula para resolver las dudas manifestadas por ellos. Denominamos a esta metodologia ‘aula inver-tida adaptativa’. El aula invertida logra un mayor grado de implicacion de los alumnos con su aprendizaje, mejoras en la valoracion de su percepcion sobre la docencia recibida y, sobre todo, mejoras en sus resultados academicos. En este ar-ticulo tambien se sopesan los benefi cios y los costes del cambio desde la metodologia expositiva tradicional al aula inver-tida adaptativa y, fi nalmente, se aportan recomendaciones para la puesta en practica del aula invertida en el contexto de una ensenanza tradicional de las ciencias sanitarias. EnglishFlipped classroom means that students have the fi rst exposure to new information to be learned outside the classroom by mean of electronic documents (texts and videos). Next, class time is devoted to class activities which reinforce the assimilation of that knowledge by applying it to answer questions and solving cases and problems. This learning model reduces the class time devoted to direct instruction and increases the time used in active learning. It transfers to the student the responsibility of initially striving to reach a basic understanding and communicate their diffi culties and doubts to the teacher. Thus, the teacher receives information about the diffi culties and needs of their students and can adapt the activities they will carry out in the classroom to solve the doubts expressed by their students. We named this teaching methodology as adaptive fl ipped classroom. The fl ipped classroom achieves a greater degree of involvement of students with their learning, improvements in academic results and in their assessment of the teaching received. In this report, the benefi ts and costs of the change are weighed from the traditional expositive methodology to the adaptive fl ipped classroom and, fi nally, recommendations are given for the implementation of the fl ipped classroom in the context of a traditional teaching of health sciences.

espanolEn este articulo examinamos las distintas utilidades de la evaluacion del aprendizaje y planteamos los conflictos que puede producir el querer enfatizar demasiado ciertas utilidades secundarias al coste del detrimento de otras mas relevantes y caracteristicas de cada tipo de evaluacion. Siguiendo a Cees van der Vleuten (autor premiado en 2012 con el Karolinska Prize for Research in Medical Education) [1] proponemos como solucion el llegar a un compromiso fundamentado que nos permita comprometer unas caracteristicas u otras de la evaluacion en funcion de la utilidad principal que pretendemos lograr por medio de esta [2,3]. Se revisan las caracteristicas de los instrumentos de evaluacion y se describe la funcion de utilidad de un metodo de evaluacion. Se discute la dicotomia entre dos tipos de evaluacion: la evaluacion formativa y de baja repercusion versus la evaluacion acreditativa y de alta repercusion. Se establecen las caracteristicas que son irrenunciables y no se pueden comprometer en cada uno de estos dos tipos de evaluacion. Estas caracteristicas esenciales irrenunciables son la validez, la fiabilidad y la seguridad en la evaluacion acreditativa o de alta repercusion (HighStakes Assessment), mientras que en la evaluacion formativa de baja repercusion (Low Stakes Assessment) no podemos comprometer el impacto educativo que incluye el estimulo del trabajo del alumno, el ejercicio de competencias y el feedback correctivo. EnglishIn this manuscript the different utilities of learning assessment and conflicts that can be caused by putting excessive emphasis to certain secondary utilities of learning assessment in detriment of another more relevant utilities for a certain type of assessment. Following to assessment expert Cees van der Vleuten [1] (awarded in 2012 with the Karolinska Prize for Research in Medical Education) we propose to reach a compromise which allows us to compromise certain assessment characteristics depending on the main utility of each type of assessment [2, 3]. Characteristics of assessment instruments are reviewed and a function of utility for a given assessment method is described. The dichotomy between the two main types of learning assessment: formative or low stakes assessment versus accreditive assessment or high stakes assessment. Essential characteristics which cannot be compromised in each one of those types of assessment are stablished. These essential characteristics are the validity, the reliability and the security in the summative or High Stakes Assessment, whereas in the formative or Low Stakes Assessment we cannot compromise the educative impact which includes both the stimulation of student work, the exercising of competences and the administration of corrective feedback.