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INTRODUCTION AND OBJECTIVE:Current standard imaging procedures have limited ability to predict lymph node metastases (LNMs) in clinically localized prostate cancer (PCa) and extended pelvic lymph n...

To assess multiparametric magnetic resonance imaging (mpMRI) characteristics in prostate cancer (PCa) before and after irreversible electroporation (IRE) and to investigate their correlation with the presence of post-operative recurrence of PCa.MpMRI was performed in 30 men with PCa prior to treatment, after 10 days and at 6 months. An additional scan at 1 year was available for 18 men. Two radiologists assessed retrospectively the following parameters by planimetry: tumour volume, necrotic volume (early post-treatment scan) and residual fibrosis. Residual tumour/recurrence were defined as a suspicious area within the treatment field scored ≥ 4 on a 1-to-5 scale. Oncological outcome was also assessed.The median follow-up of the entire study was 16 months. Six men were undertreated and showed mpMRI recurrence after 6 months. At 1-year, three additional men had recurrence. Overall, four of these 9 men (44%) were retreated. The other five men did not receive any further treatment. Median time to re-treatment was 15 months. Median pre-treatment lesion volume was 0.65 cc, 0.66 cc and 0.43 cc on the different mpMRI sequences (T2-weighted, diffusion-weighted and dynamic contrast enhanced imaging). Median necrotic volume was 10.77 cc. Median overall residual fibrosis volumes were 0.84 cc and 0.95 cc at 6-month and 1-year mpMRI. Pre-treatment, necrotic and residual fibrosis volumes were significantly different (p 0.001). Pre-treatment tumour volumes on diffusion-weighted imaging and necrotic volumes were correlated (r = 0.18; p = 0.02).MpMRI is able to visualise the IRE ablation effects in men with PCa. MpMRI-derived parameters - such as tumour, necrotic and fibrosis volumes - can be measured and are potentially useful for assessing efficacy in the medium term, as with other ablative techniques.

Resumen El desenlace de la infeccion por SARS-CoV-2 (COVID-19) afecta fundamentalmente al campo pulmonar, ocasionando un cuadro de sindrome de distres respiratorio agudo (SDRA). Este proceso es un cuadro inflamatorio protagonizado por una cascada de citocinas bajo el amparo del inflamasoma NLRP3, responsable principal de la destruccion alveolar. De entre todas las citocinas que se desencadenan en este cuadro destaca la IL-1s. Anakinra es un potente farmaco biologico, capaz de bloquear esta IL-1s. Proponemos su uso, de cara a controlar el SDRA secundario a la infeccion por COVID-19.

The outcome of the SARS-CoV-2 (COVID-19) infection fundamentally affects the lung field, causing ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS). This process is an inflammatory picture, involving an NLRP3 INFLAMOSOME-triggered cytokine storm, the main player in alveolar destruction. IL-1 beta stands out among the cytokines that are triggered in this picture. ANAKINRA is a potent biological drug, capable of blocking this IL 1 beta. We propose its use in controlling ARDS secondary to COVID-19 infection.

Background: This prospective multicenter study developed an integrative clinical and molecular longitudinal study in Rheumatoid Arthritis (RA) patients to explore changes in serologic parameters following anti-TNF therapy (TNF inhibitors, TNFi) and built on machine-learning algorithms aimed at the prediction of TNFi response, based on clinical and molecular profiles of RA patients.Methods: A total of 104 RA patients from two independent cohorts undergoing TNFi and 29 healthy donors (HD) were enrolled for the discovery and validation of prediction biomarkers. Serum samples were obtained at baseline and 6 months after treatment, and therapeutic efficacy was evaluated. Serum inflammatory profile, oxidative stress markers and NETosis-derived bioproducts were quantified and miRNomes were recognized by next-generation sequencing. Then, clinical and molecular changes induced by TNFi were delineated. Clinical and molecular signatures predictors of clinical response were assessed with supervised machine learning methods, using regularized logistic regressions.Results: Altered inflammatory, oxidative and NETosis-derived biomolecules were found in RA patients vs. HD, closely interconnected and associated with specific miRNA profiles. This altered molecular profile allowed the unsupervised division of three clusters of RA patients, showing distinctive clinical phenotypes, further linked to the TNFi effectiveness. Moreover, TNFi treatment reversed the molecular alterations in parallel to the clinical outcome. Machine-learning algorithms in the discovery cohort identified both, clinical and molecular signatures as potential predictors of response to TNFi treatment with high accuracy, which was further increased when both features were integrated in a mixed model (AUC: 0.91). These results were confirmed in the validation cohort.Conclusions: Our overall data suggest that: 1. RA patients undergoing anti-TNF-therapy conform distinctive clusters based on altered molecular profiles, which are directly linked to their clinical status at baseline. 2. Clinical effectiveness of anti-TNF therapy was divergent among these molecular clusters and associated with a specific modulation of the inflammatory response, the reestablishment of the altered oxidative status, the reduction of NETosis, and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.

Resumen Objetivos Desarrollar recomendaciones sobre el uso de metrotexato (MTX) parenteral en pacientes con enfermedades reumaticas, fundamentalmente en la artritis reumatoide, basadas en la mejor evidencia y experiencia. Metodos Se selecciono un grupo de 21 expertos reumatologos en el manejo de MTX. El coordinador genero 13 preguntas sobre el uso de MTX parenteral (perfiles de indicacion, eficacia, seguridad, costo-eficacia y biodisponibilidad) para ser contestadas mediante una revision sistematica de la literatura. Con base en las preguntas se definieron los criterios de inclusion y exclusion, y las estrategias de busqueda (en Medline, EMBASE y la Cochrane Library). Tres revisores seleccionaron los articulos resultantes de la busqueda. Se generaron tablas de evidencia. Paralelamente se evaluaron abstracts de congresos de la European League Against Rheumatism (EULAR) y del American College of Rheumatology (ACR). Con toda esta evidencia el coordinador genero 13 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunion del grupo nominal con los expertos. Para cada recomendacion se establecio el nivel de evidencia y grado de recomendacion, y el grado de acuerdo mediante un Delphi. Se definio acuerdo si al menos el 80% de los participantes contestaron si a la recomendacion (si o no). Resultados La mayoria de la evidencia proviene de la artritis reumatoide. De las 13 recomendaciones preliminares se aceptaron 11 recomendaciones sobre el uso de MTX parenteral en reumatologia. Dos no se llegaron a votar y se decidio no incluirlas, pero se comentan en el texto final. Conclusiones Este documento pretende resolver algunos interrogantes clinicos habituales y facilitar la toma de decisiones con el uso de MTX parenteral.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation and tissue damage mediated by the immune system. Respiratory manifestations are common in SLE, appearing in up to 50% of patients throughout their lives. Furthermore, it is associated with higher mortality. Objectives: To describe the prevalence and characteristics of pulmonary involvement in patients with SLE Methods: Observational, descriptive, cross-sectional, retrospective study performed in patients with SLE in follow-up by the Rheumatology Department of Valme Hospital. The following information is collected from medical records; age, sex, mean age at diagnosis, characteristics of pleuropulmonary involvement and ANA and antiDNA positivity. Results: We studied 165 patients with SLE, with mean age of 37.01 +/- 14.65 years, predominance of the female patients 153 (92.72%). Thirty eight of them had pulmonary involvement (23.03%), with a total of 47 episodes related to lung manifestations. Mean age at diagnosis was 39.70 +/- 15.50 years. Below is shown information about lung involvement: Eleven patients (28.94%) presented pulmonary involvement at the time of diagnosis; pleuritis (10.63%) and only one case of interstitial lung disease, varicella pneumonia, shrinking lung syndrome, pulmonary embolism (PE) and bronchiolitis obliterans with organizing pneumonia. Two patients (4.24%) died due to severe respiratory failure secondary to bilateral pneumonia. Three of the 5 patients with PE were diagnosed with antiphospholipid syndrome secondary to SLE. Regarding treatment, most of patients who required hospitalization were in basic treatment with synthetic DMARDs (78.57% in monotherapy and 21.43% with double therapy) and only 2 patients with biologic DMARDs (Rituximab and etanercept). Six patients had no treatment because the pulmonary event was at time of diagnosis, 2 patients were with antiaggregating therapy and there was no information registered in two patients (episode before 1997). 91.10% of the patients presented positive for ANA, of which 37.14% (13 patients) also presented positive antiDNA. No information was collected about autoimmunity in one patient (2.12%). Conclusion: Pulmonary involvement in SLE is prevalent, although a significant proportion may remain asymptomatic. The little prevalence of pulmonary manifestations in our series might be due to low mean age, according to the result of a recent systematic review where analysed more than 10000 patients and concluded pulmonary manifestations are more frequent in late-onset SLE. The differential diagnosis is broad and the infectious cause, the main cause of mortality in patients with SLE, must always be ruled out. References: [1] 10.1016/j.semarthrit.2018.01.010 [2] 10.1016/j.reuma.2018.03.012 [3] 10.1186/s13075-018-1776-8 [4] 10.1097/BOR.0000000000000531 Acknowledgement: None Disclosure of Interests: NAHIA PLAZA: None declared, MARIA JOSE PEREZ: None declared, Sergio Rodriguez Montero: None declared, CARMEN TRAPERO: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen

Background The infection of a native or prosthetic heart valve usually occurs in patients with structural valvular anomalies that predispose to turbulent flows. Manifestations such as arthralgia, arthritis or back pain appear in up to 40% of patients, which acts as a confounding factor when this infection occurs in patients with rheumatic diseases. On the other hand, in the latter patients, noninfectious endocarditis has been described, which adds even more complexity to the diagnosis. Objectives To describe the characteristics of endocardial lesions in patients with rheumatic diseases. Methods Patients attending clinics at the Department of Rheumatology were analyzed to determine how many of them required hospitalization for causes directly related to endocardial lesion, from January 2015 until December 2018. The following information was recorded: age, sex, type of rheumatic disease, duration of the disease, immunosuppressive treatment, characteristics of endocardial lesions, complications of endocardial lesions, and cardiovascular risk factors. Results All patients were identified from an electronic database. Results regarding to demographic and clinical data are as follows: Conclusion The spectrum of endocardial involvement in patients with rheumatic diseases is variable. In this case review, we found lesions of different origin: infectious, thrombotic and tumoral. The appearance of fever of unknown origin in patients with rheumatic diseases, requires ruling out an endocarditis, needing transesophageal echocardiography in case the transthoracic study, which is less sensitive, is negative. It is striking the case of patient 3, a systemic sclerosis with calcinosis in limbs, whose endocardial wart, was studied histologically, revealing in its composition mainly calcium and fibrin. We have not found a bibliographic reference of calcium endocarditis in systemic sclerosis. In conclusion, patients with rheumatic diseases can develop infectious endocarditis, but also thrombotic valvular vegetations, as well as myxomas whose consequences, from their clinical debut, may pose life-threatening situations for the patient. The presence of fever, stroke or embolic events in these patients should put us on the track of an underlying endocardial involvement. References [1] Am J Med (2007) 120, e1-e2 [2] World J Cardiol 2014 September 26; 6(9): 993-1005 [3] Rev Esp Enferm Metab oseas 2002;11(2): 50-58 Disclosure of Interests Sergio Rodriguez Montero: None declared, Consuelo Ramos Giraldez Speakers bureau: Sanofi, NAHIA PLAZA: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen

Objectives: To estimate the incidence of cancer in systemic lupus erythematosus (SLE) patients and to analyze factors associated with cancer differentiating between hormone-sensitive (HS) and non-HS cancers. Methods: Multicenter retrospective study of a cohort of patients included in Spanish Society of Rheumatology Lupus Registry (RELESSER). The first cancer after the diagnosis of SLE, sociodemographic, clinical, activity, cumulative damage, severity, comorbidity, treatments, and refractory disease data were collected. Cancers were classified into HS (prostate, breast, endometrial and ovarian) and non-HS (the rest). Standardized incidence ratio (SIR) was calculated and logistics regression models were constructed to identify factors associated with cancer. Results: We included 3539 patients (90.4% women) with SLE (ACR-97 criteria), of whom 154 had cancer (91% women), and 44 were HS (100% women). The SIR for cancer was 1.37 (95% CI: 1.15-1.59), reaching higher values in women under 65 years [2.38 (95% CI: 1.84-2.91)]. The SIR in women with cancer HS vs. non-HS was 1.02 (95% CI: 0.13-1.91) and 1.93 (95% CI: 0.98-2.89)], respectively. In HS vs. non-HS cancers, age at diagnosis of SLE [Odds ratio (OR) 1.04 (p = 0.002) vs. 1.04 (p = 0.019), respectively] and the evolution time [OR 1.01 (p Conclusion: The incidence of cancer in patients with SLE is increased compared to the Spanish population, specially in younger women. This increase might be due to non-HS cancers. SLE with more cumulative damage and more prescription of ACE inhibitors might associate with non-HS cancers. Disclosure of Interests: Tatiana Cobo-Ibanez: None declared, ANA URRUTICOECHEA-ARANA: None declared, Inigo Rua-Figueroa: None declared, Maria Auxiliadora Martin-Martinez: None declared, Juan Ovalles: None declared, Maria Galindo-Izquierdo: None declared, Jaime Calvo-Alen: None declared, Alejandro Olive: None declared, Antonio Fernandez-Nebro: None declared, Raul Menor-Almagro: None declared, Eva Tomero Muriel: None declared, Loreto Horcada: None declared, Esther Uriarte Isacelaya: None declared, Victor Martinez Taboada: None declared, Jose Luis Andreu: None declared, Alina Boteanu: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Cristina Bohorquez: None declared, Carlos A. Montilla-Morales: None declared, Gregorio Santos Soler: None declared, Blanca Hernandez-Cruz: None declared, Paloma Vela-Casasempere Grant/research support from: UCB, Abbvie, Pfizer, Roche, Bristol-Myer-Squibb (another research, not BIOBADASER related), Consultant for: UCB, Lilly, Pfizer, Roche, Bristol-Myer-Squibb, Speakers bureau: Roche, UCB, MSD, Pfizer, GSK, BMS, Lilly, Eva Salgado Perez: None declared, Mercedes Freire Gonzalez: None declared, Jose A Hernandez Beriain: None declared, Elvira Diez Alvarez: None declared, Lorena Exposito: None declared, Olaia Fernandez- Berrizbeitia: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen, Jose M Pego-Reigosa: None declared

Background: In the last years multiple genetic variants have been associated with autoimmune disease (AD) risk. However, much less is known on the association with important environmental factors like diet. Objectives: The objective of the present study is to characterize the dietary patterns of six prevalent ADs, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE). Methods: A cross-sectional cohort of 11,621 individuals from Spain encompassing 1,949 RA, 2,186 psoriasis (PS), 1,437 PsA, 699 SLE, 1,415 ulcerative colitis (UC), 1,952 Crohn’s disease (CD) and 1,983 healthy controls, was recruited by the IMID-Consortium. The weekly consumption frequency of main food categories was recorded, together with drinking habits and smoking status. Multivariate linear models were used to test for association while adjusting for confounders. Results: Patients with AD targeting the digestive system showed the largest differences in comparison to controls. In the rheumatic ADs several food categories were also found to be consumed differently compared to controls. SLE had a high consumption of sweets and pastries, and RA ate more fruit and bread/wholegrain foods and less meat and cold cuts compared to controls. In PsA the dietary pattern differences with controls where milder, and non-overlapping with psoriasis. Disease activity was significantly associated with specific food categories in CD, UC and PS, mildly in RA and SLE, and PsA showed no association. High smoking cessation rates were observed in UC, CD and SLE, but not in Ps, RA and PsA. Tea/coffee and alcohol consumption was low in all ADs compared to controls. Conclusion: Our results show previously unreported associations with dietary habits in rheumatic ADs. Disclosure of Interests: Antonio Julia: None declared, Sergio Hilario Martinez: None declared, Jesus Tornero: None declared, Juan D. Canete: None declared, Antonio Fernandez-Nebro: None declared, Francisco Blanco: None declared, Jesus Rodriguez: None declared, Francisco J Lopez-Longo: None declared, Benjamin Fernandez-Gutierrez: None declared, Jordi Gratacos: None declared, Jose Javier Perez Venegas: None declared, Carolina Perez: None declared, Ruben Queiro Silva: None declared, Alejandro Olive: None declared, Mercedes Alperi-Lopez: None declared, Carlos A. Montilla-Morales: None declared, Jose Luis Andreu: None declared, Juan Carlos Torre-Alonso: None declared, M Angeles Aguirre-Zamorano: None declared, Hector Corominas: None declared, Paloma Vela Casasempere: None declared, Victor Martinez Taboada : None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., Joan Miquel Nolla: None declared, Isidoro Gonzalez-Alvaro: None declared, Santiago Munoz-Fernandez: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen, Carlos M. Gonzalez: None declared, Antonio Zea: None declared, Maria Lopez Lasanta: None declared, Daniel Roig: None declared, Jose M Pego-Reigosa: None declared, Mireia Lopez Corbeto: None declared, Pedro Zarco-Montejo: None declared, Mercedes Freire Gonzalez: None declared, Alba Erra: None declared, Elvira Diez Alvarez: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Esther Rodriguez Almaraz: None declared, Alicia Garcia: None declared, Patricia Carreira: None declared, GEORGINA SALVADOR ALARCON: None declared, Cesar Diaz Torne Consultant for: Grunenthal, Speakers bureau: Grunenthal, Ricardo Blanco: None declared, Alfredo Willisch Dominguez: None declared, Jose Antonio Mosquera Martinez: None declared, Simon Sanchez Fernandez: None declared, Julio Ramirez: None declared, Sara Marsal: None declared

Objectives. This article estimates the frequency of polyautoimmunity and associated factors in a large retrospective cohort of patients with SLE. Methods. RELESSER (Spanish Society of Rheumatology Lupus Registry) is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. The main variable was polyautoimmunity, which was defined as the co-occurrence of SLE and another autoimmune disease, such as autoimmune thyroiditis, RA, scleroderma, inflammatory myopathy and MCTD. We also recorded the presence of multiple autoimmune syndrome, secondary SS, secondary APS and a family history of autoimmune disease. Multiple logistic regression analysis was performed to investigate possible risk factors for polyautoimmunity. Results. Of the 3679 patients who fulfilled the criteria for SLE, 502 (13.6%) had polyautoimmunity. The most frequent types were autoimmune thyroiditis (7.9%), other systemic autoimmune diseases (6.2%), secondary SS (14.1%) and secondary APS (13.7%). Multiple autoimmune syndrome accounted for 10.2% of all cases of polyautoimmunity. A family history was recorded in 11.8%. According to the multivariate analysis, the factors associated with polyautoimmunity were female sex [odds ratio (95% CI), 1.72 (1.07, 2.72)], RP [1.63 (1.29, 2.05)], interstitial lung disease [3.35 (1.84, 6.01)], Jaccoud arthropathy [1.92 (1.40, 2.63)], anti-Ro/SSA and/or anti-La/SSB autoantibodies [2.03 (1.55, 2.67)], anti-RNP antibodies [1.48 (1.16, 1.90)], MTX [1.67 (1.26, 2.18)] and antimalarial drugs [0.50 (0.38, 0.67)]. Conclusion. Patients with SLE frequently present polyautoimmunity. We observed clinical and analytical characteristics associated with polyautoimmunity. Our finding that antimalarial drugs protected against polyautoimmunity should be verified in future studies., The RELESSER Registry was partially funded by GlaxoSmithKline (GSK), Roche, Union Chimique Belge (UCB), Lilly and Novartis. The sponsors had no role in the study design, data collection, analysis or interpretation, in writing the report, or in the decision to submit the article for publication. J.M.P.-R. is supported by grant 316265 (BIOCAPS) from the European Union 7th Framework Program (FP7/REGPOT-2012-2013.1). The study was supported by FIS Grant PI11/02857 (Instituto Carlos III, Fondos FEDER). Grant for medical researchers of the 'Fundacion Espanola de Reumatologia'.

Background: Efficacy and safety of the new JAK inhibitors is supported by phase I, II and III studies with a large number of patients included in the follow-up, although it is of vital importance behavior of new molecules in routine clinical practice, and until now we still have few clinical data. Objectives: To describe the adverse effects observed, as well as the income Hospitals and description of them during treatment with JAK inhibitors in a series of patients with RA. Methods: This is a retrospective descriptive study in patients with RA treated with JAK inhibitors in follow-up by the Rheumatology Unit of Virgen de Valme Hospital. We included demographic, related to the disease and treatment and security variables. Results: We included 31 patients with rheumatoid arthritis with a mean age of 57.58 ± 11.31 years and mean time of evolution of the disease of 9.42 ± 6.62 years, 61.3% positive FR and 61.3% ACPA positive. The female sex represents 74.2% of the sample. The mean of the baseline DAS28 was 4.90 ± 0.95. Regarding the treatment analysis initiated 12 patients (38.7%) receive baricitinib and 19 (61.3%) tofacitinib. 93.5% were in treatment with steroids at low doses and 80.64% in treatment combined with at least 1 associated DMARD (75% baricitinib group, 84.2% tofacitib group). The subanalysis of concomitant treatment reveals that up to 31.5% of patients undergoing treatment with tofacitinib initiated treatment with ≥2 FAMEs. 61.3% of patients had previously received at least one biological drug, among which the antiTNFs stand out for their frequency; 31.5% with one biological, 9.7% with 2 previous biologicals and 16.5% had used three. A total of 14 adverse effects were recorded in 10 of the 31 patients which are described below: baricitinib group a total of 6 events (50%); 1 toxic hepatitis, 1 respiratory infection, 2 cases of urinary tract infection, 1 case of canker sores, and 1 cold sore. Tofacitinib group a total of 8 events (42.1%): 2 cases of Herpes zoster, 1 case of headache and dizziness, 2 perianal abscesses and 1 abscess submandibular There were 3 hospital admissions with independence of its relationship with the treatment analyzed; barcitinib group: 1 patient with upper respiratory tract infection and decompensated heart failure, 1 patient with toxic hepatitis. Tofacitinib group: 1 patient with post-traumatic humerus fracture. Conclusion: The main side effect observed was infection, in general mild-moderate that only motivated hospital admission in a patient in treatment with barcitinib due to decompensation of its pathology base. Stresses the development of uncomplicated perianal abscess in 2 patients on treatment with tofacitinib, one of them with perianal fistula known, and a recurrence of submental abscess in a patient with antecedent of repetition abscesses in said location. I only know observed elevated transaminases in a patient undergoing treatment with baricitinib showing in general an optimal hepatic safety profile. No primary cardiovascular events of interest have been recorded, neoplasms or other gastrointestinal events. Everything described, considering the high rate of concomitant treatment with steroids at low doses (93.5%) and up to 80.64% of patients in treatment with at least 1 concomitant DMARD. References [1] Caporali R, Zavaglia D : Real-world experience with tofacitinib for treatment of rheumatoid arthritis. Clin Exp Rheumatol. 2018 Aug 29. [2] Fleischmann R, Mysler E, Hall S Et Al.: Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet 2017; 390: 457-68. [3] Smolen JS, Genovese MC, Takeuchi T, et al. Safety profile of baricitinib in patients with active rheumatoid arthritis with over 2 years median time in treatment [published online September 15, 2018]. J Rheumatol. Disclosure of Interests: Natalia Cid Boza: None declared, ML Velloso Feijoo: None declared, NAHIA PLAZA: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen

Background Antiphospholipid syndrome (APS) is characterized by spontaneous and recurrent vascular thromboses, abortion and thrombocytopenia. Cardiac manifestations are rare, but may occur as cardiac masses, such as thrombus (Libman-Sacks endocarditis). On the other hand, it is known that the most common type of primary cardiac tumors, myxoma, can produce clinical pictures similar to APS and SLE, and that tumor exeresis resolves symptoms. Methods We examined 2 patients diagnosed with SLE and APS that presented cardiac mass. They were assessed with careful history taking, physical examination, laboratory tests, echocardiography and histological examination. Results Case 1. A 13-years-old girl, with history of autoimmune hemolytic anemia treated with corticosteroids, folic acid and splenectomy a year before, presented a right ischemic stroke with hemiparesis sequel. Laboratory tests revealed ANA, antiDNAds, aCL and lupus anticoagulant positive and echocardiography showed a cardiac mass. She was underwent surgery to exeresis the mass, which was compatible with myxoma. She was diagnosed with immune syndrome secondary to myxoma and did not take treatment. Seven months after the complete exeresis of the myxoma, she was admitted to our hospital because of two months fever, polyarthralgia, oral ulcers and malar rash. Echocardiography showed pericardial effusion and blood tests showed lymphopenia, anemia, ANA and antiDNA positive and elevation of acute phase reactants; urinalysis was normal. She was diagnosed with SLE flare and was successfully treated with corticoids and started hydroxychloroquine, azathioprine and acetylsalicylic acid. The second case is a 48-years-old woman diagnosed with SLE and associated APS (oral ulcers, thrombosis, arthritis, malar rash, ANA, Coombs and aCL positive), with a history of bilateral iliac arterial ischemia caused by myxoma emboli (confimated by histological examination) and a cardiac mass on echocardiogram. Fourteen months after the vascular surgery, the patient still needs treatment with rituximab, azathioprine and corticoids to control SLE activity and is on anticoagulant treatment to prevent thrombotic episodes. Conclusions In patients with myxoma and symptoms of APS and/or SLE, there is doubt whether these are secondary to myxoma or if these diseases coexist, so it is recommended to closely monitor clinical activity after exeresis of myxoma and consider not suspending immunosuppressants and/or anticoagulants or the progressive withdrawal of drugs according to symptoms, in order to avoid possible serious complications of autoimmune disease. Funding Source(s): None

Background The primary antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis and pregnancy morbidity in the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA). In addition to prothrombotic effects of aPL on the brain, there are immunologic effects with proof of direct binding of aPL to various types of brain cells, presented as cognitive dysfunction (CD),migraine,seizure, multiple sclerosis-like syndrome (MS-like), transverse myelitis (TM), movement disorders, or psychiatric symptoms. Methods We examined 3 patients who were diagnosed primary APS.The patients were assessed with careful history taking, physical examination, blood laboratory evaluation, andMRI or head-CT.Our main objective was to describe neurologic manifestations of APS in our patients at Valme University Hospital and the response to treatment with hydroxychloroquine Results Among the 3 patients, there was male preponderance with 3 men and no-women.The mean age of presentation was 33.66±5.2 years (range, 23 50 years) and with a current mean age of 37±14,93 years.There was no mortality in our series. One of them debuted with sudden loss of consciousness along with jaw stiffness and posterior amnesia.The other one presented prickling sensation and involuntary movement of his right upper limb extending to right lower limbs without posterior generalization, and the third patient consulted with frontal, pulsating headache and binocular diplopia.100% were LA positive with prolongated Activated Partial Thromboplastin Time and dilute Russell viper venom time and negative for ANA with no collagenosis sign or symptoms. Neither presented complement alteration or cerebrospinal fluid variation.We observed positivity for aCL in one patient (33%). In 2 of 3 patients (66.66%), cortico-subcortical space occupant lesions (SOL) were observed, some of them with contrast enhancement, mimicking demyelinating lesion, while the other patient didn’t present any abnormality in the MRI images.All patients presented an appropriate response to treatment with prednisone,in downward treatment regimen, aspirin and hydroxychloroquine 200 mg twice a day. At the four-year follow-up, all of them remain asymptomatic.We observed a lessening of SOL in MRI images due to the treatment in two patients but the third one presented new lesions due to suspension od prednisone, which was reintroduced, lessening of SOL. Conclusions The neurological affection presented in APS can mimic multiple sclerosis symptoms and it is difficult to differentiate both entities That is why aPL determination should be part of screening tests and should not be delayed if the diagnosis of APS is suspected.Hydroxychloroquine could be a valid treatment in CNS manifestations in patients with APS Funding Source(s): None

The goal of radical prostatectomy is to eradicate oncological disease while achieving the best possible functional outcomes. In this regard, nerve sparing offers a greater chance of recovering potency after surgery. Accurately locating prostate cancer foci is instrumental for identifying good candidates for this approach whilst maintaining safe oncological margins. In addition to this, the length of membranous urethra is an independent predictor of time to, and extent of, continence recovery. The introduction of Mp-MRI allows visualising malignant tissue within the prostate gland, which could lead to image-directed surgery planning as with other solid-organ cancers such as kidney, pancreas, breast or testes. A narrative review of the available literature was performed. Mp-MRI demonstrated moderate sensitivity and high specificity to detect extra-capsular extension, seminal vesicle involvement or T3 stage. Measurements of membranous urethral length have shown to be useful in predicting probability of achieving continence after surgery. Furthermore, image-guided surgery has shown to be accurate to determine surgical planes to safely preserve neurovascular bundles. The use of Mp-MRI for pre-surgical planning introduces a new scenario where the previously homogeneous radical prostatectomy can be tailored to suit patient and tumour features. This has the potential to improve functional outcomes whilst not compromising on surgical margins. Moreover, the introduction of Mp-MRI increases the ability to predict functional outcomes after surgery and allows for a more accurate local staging. This in turn provides more information to both patients and clinicians in the decision-making process regarding treatment.

Background: Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease with a complex genetic inheritance. Genome-wide association studies (GWAS) have significantly increased the number of significant loci associated with SLE risk. To date, however, established loci account for less than 30% of the disease heritability and additional risk variants have yet to be identified. Here we performed a GWAS followed by a meta-analysis to identify new genome-wide significant loci for SLE. Methods: We genotyped a cohort of 907 patients with SLE (cases) and 1524 healthy controls from Spain and performed imputation using the 1000 Genomes reference data. We tested for association using logistic regression with correction for the principal components of variation. Meta-analysis of the association results was subsequently performed on 7,110,321 variants using genetic data from a large cohort of 4036 patients with SLE and 6959 controls of Northern European ancestry. Genetic association was also tested at the pathway level after removing the effect of known risk loci using PASCAL software. Results: We identified five new loci associated with SLE at the genome-wide level of significance (p < 5 × 10? 8): GRB2, SMYD3, ST8SIA4, LAT2 and ARHGAP27. Pathway analysis revealed several biological processes significantly associated with SLE risk: B cell receptor signaling (p = 5.28 × 10? 6), CTLA4 co-stimulation during T cell activation (p = 3.06 × 10? 5), interleukin-4 signaling (p = 3.97 × 10? 5) and cell surface interactions at the vascular wall (p = 4.63 × 10? 5). Conclusions: Our results identify five novel loci for SLE susceptibility, and biologic pathways associated via multiple low-effect-size loci. This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36). This work has been also sponsored by the grant SEV-2011-00067 of Severo Ochoa Program, awarded by the Spanish Government. This work was supported by an EFSD/Lilly research fellowship. Josep M. Mercader was supported by Sara Borrell Fellowship from the Instituto Carlos III. Sílvia Bonàs was awarded an FI-DGR Fellowship from FI-DGR 2013 from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya). The study sponsors had no role in the design of the study, collection, analysis or interpretation of the data.

Objectives To assess the efficacy and safety of golimumab in the 140 patients included in Spain as the first part of the GO-MORE trial, a multinational study involving patients with active rheumatoid arthritis (RA) despite treatment with different disease-modifying antirheumatic drugs (DMARDs). Patients and methods The patients received subcutaneous golimumab 50 mg once a month during 6 months. The primary endpoint was the percentage of individuals with a good or moderate EULAR DAS28-ESR response after 6 months of treatment. Results A total of 140 patients were included. Of these, 76.4% had very active disease (DAS28-ESR >5.1). 76.4% were taking methotrexate, 40.0% other DMARDs in monotherapy or combined, and 65.0% received corticosteroids. After 6 months, 82.9% of the patients showed a good or moderate EULAR response, 41.4% had low disease activity, and 30.7% were in remission. The percentage of responders one month after the first dose was 69.3%. The efficacy was similar in patients treated with methotrexate or other DMARDs, with different methotrexate doses, with or without corticosteroids, or in subjects who had failed one or more DMARDs. The response to golimumab was observed from the first dose. Golimumab was well tolerated and its safety profile was consistent with the findings of previous studies. Serious adverse events were reported in 11 patients (7.9%). Conclusion The addition of subcutaneous golimumab 50 mg once a month to different DMARDs in patients with active RA yielded a moderate or good response after 6 months in 82.9% of the cases. The response was observed early, from the start of the second month, after a single dose of golimumab.

Objective To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience. Methods A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text. Conclusions The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX.

Background: Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. Methods: A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. Results: In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR ) < 0.05), and between the negative regulation signaling pathway of retinoic acid inducible gene-I/melanoma differentiation associated gene 5 and the production of antinuclear antibodies (P FDR < 0.05). In the replication stage, we validated the association between the VEGF pathway and oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. Conclusions: The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis of phenotype heterogeneity in SLE, This study was funded by the Spanish Ministry of Economy and Competitiveness (grant numbers: PSE-010000-2006-6 and IPT-010000-2010-36 and by the “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR, Generalitat de Catalunya, FI-DGR 2016, grant number: 00587)

Patients who have had inadequate response to tumour necrosis factor inhibitors have fewer treatment options and are generally more treatment refractory to subsequent therapeutic interventions than previously untreated patients. We report the efficacy and safety of ixekizumab, a monoclonal antibody that selectively targets interleukin-17A, in patients with active psoriatic arthritis and previous inadequate response to tumour necrosis factor inhibitors.In this double-blind, multicentre, randomised, placebo-controlled, phase 3 study (SPIRIT-P2), patients were recruited from 109 centres across ten countries in Asia, Australia, Europe, and North America. Patients were aged 18 years or older, had a confirmed diagnosis of psoriatic arthritis for at least 6 months, and had a previous inadequate response, distinguished by being refractory to therapy or had loss of efficacy, or were intolerant to tumour necrosis factor inhibitors. Patients were randomly assigned (1:1:1) by a computer-generated random sequence to receive a subcutaneous injection of 80 mg ixekizumab every 4 weeks or every 2 weeks after a 160 mg starting dose or placebo. The primary endpoint was the proportion of patients who attained at least 20% improvement in the American College of Rheumatology response criteria (ACR-20) at week 24. This study is registered with ClinicalTrials.gov, number NCT02349295.Between March 3, 2015, to March 22, 2016, 363 patients were randomly assigned to placebo (n=118), ixekizumab every 4 weeks (n=122), or ixekizumab every 2 weeks (n=123). At week 24, a higher proportion of patients attained ACR-20 with ixekizumab every 4 weeks (65 [53%] patients; effect size vs placebo 33·8% [95% CI 22·4-45·2]; p0·0001) and ixekizumab every 2 weeks (59 [48%] patients; 28.5% [17·1-39.8]; p0·0001) than did patients with placebo (23 [20%] patients). Up to week 24, serious adverse events were reported in three (3%) patients with ixekizumab every 4 weeks, eight (7%) with ixekizumab every 2 weeks, and four (3%) with placebo; no deaths were reported. Infections were reported in 47 (39%) patients with ixekizumab every 4 weeks, 47 (38%) with ixekizumab every 2 weeks, and 35 (30%) with placebo. Three (2%) serious infections, all in patients in the ixekizumab every 2 weeks group, were reported.Both the 2-week and 4-week ixekizumab dosing regimens improved the signs and symptoms of patients with active psoriatic arthritis and who had previously inadequate response to tumour necrosis factor inhibitors, with a safety profile consistent with previous studies investigating ixekizumab.Eli Lilly and Company.

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown and multifactorial aetiology, whose prevalence is around 1% of the adult population. It most commonly affects women between the 4th and 6th decade. Patients with RA have an increased cardiovascular morbidity and mortality (CV) being the main cause of death. “Systematic Coronary Risk Evaluation” (SCORE) allows us to estimate the risk of death from cardiovascular disease as 10 years. Objectives To evaluate whether the presence of anti-peptide citrullinated (ACPA) antibodies is associated with increased frequency of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) or with greater SCORE. Methods observational, analytical case-control study nested in a cohort of patients diagnosed with AR follow-up in the Valme hospital area. Cases were considered the patients who have developed a myocardial infarction or cerebrovascular or ischaemic heart disease and controls RA patients without CVD. They all determined ACPA levels, the classic cardiovascular Results A total of 260 patients were included from a database of 327 patients with AR. In 67 of these, we coudn’t get the main variables of the sutdy, and were excluded. Conclusions In our sample, unlike other published studies, we found no differences in the occurrence of cardiovascular events, or the SCORE in patients ACPA (+) v ACPA (-). While subgroups of patients with ACPA + have a greater tendency to be treated with biological therapy. This lack of differences could also be explained by the early implantation of both primary and secondary prevention of cardiovascular disease in patients with RA. References Results from systematic screening for cardiovascular risk in outpatients with rheumatoid arthritis in accordance with the EULAR recommendations; ARD Online First, published on July 12, 2013 as 10.1136/annrheumdis-2013-20368

Background The head and neck tumours are a heterogeneous group of diseases that affect the otolaryngology (ENT) sphere . It constitutes 2.9% of all new cancer cases. Predominantly affect older men aged 40 years. Smoking, excessive alcohol consumption, treatment with high doses of corticosteroids and malnutrition suffering after surgery and radiotherapy, involves a potential situation of accelerated bone loss in a young population with good long-term prognosis. Objective To describe the characteristics regarding risk factors and osteoporotic disease in patients with head and neck tumours. Material and methods An Observational study of a case series of patients with tumours of the head and neck joint monitoring in consultations of Rheumatology and Medical Oncology Hospital Valme area. We collected the following variables; age, sex, risk factors for osteoporosis and osteoporotic fracture, lateral radiography of lumbar and thoracic spine, and lumbar spine and hip bone densitometry Results 50 patients diagnosed whith head and neck tumours were included. Of these, 100% were male, with a mean age of 62 years at present. The most frequent location was the larynx in 55% of cases, followed by a 7% for those of tonsils and other locations of the oral cavity . Approximately a 16% of patients had a history of gastrointestinal pathology In relation to risk factors for both disease, tumour and osteoporosis we found : Also found two patients with vertebral fractures, one with osteoporosis and the second with osteopenia. Finally in relation to tumour pathology, 10% were stage II, candidates for treatment with radiation therapy compared with 90% remaining subsidiary of intensive treatment with chemotherapy, radiation therapy and high-dose corticosteroids. Conclusions In our sample, we found that up to 16.6% of patients and 7.1% had osteopenia or osteoporosis at baseline. Assuming that during treatment, they will suffer about 16% of loss weight, attached to treatment with high-dose corticosteroids, would justify develop measures for primary prevention of osteoporosis with a study and treatment of these patients.

Introduction Psoriasis arthritis (PSA) is a highly heterogeneous disease. Occasionally it courses with very aggressive forms that requiring biological therapies (TB). Objective To evaluate the effectiveness and long-term safety of TB in a serie of patients with PSA tracking Valme Hospital area. Methods Observational descriptive study of a series of 25 patients with diagnosis of PSA with peripheral affectation according CASPAR criteria, in treatment with TB in the UGC of Valme hospital. Measurement of disease activity using the DAS28 index before and after TB. Survival analysis of each of the biological drugs used. Evaluation of drug safety through adverse effects (EA) collection. Results a total of 25 patiens diagnosied with PSA with TB treatment were reviewed. Etanercept was the drug most used in first line (36%), followed by Infliximab (32%), Adalimumab (16%), Golimumab (12%) and Certolizumab (4%). In 2nd line of treatment, also Etanercept was the most used followed of Adalimumab. A single patient with highly refractory APS was treated with Abatacept in the fourth line and is currently being treated with Ustekinumab in the 5th line. Regarding efficacy data for the first biological: DAS 28 values before the onset of TB were: 20% High, 60% moderate, 8% low and 12% in remission (patiens in remission had the indication of TB by the cutaneous affectation). At the cut-off point after the first biology, we found: All the patients who were in remission and with low activity,becuse were wtih TB due to cutaneous involvement continued with the same values of DAS 28. The rest of the patients with TB, we found after treatment with the first drug 60% were in remission, 24% low activity and 16% remained with moderate activity. By means of the Student’s T for paired samples in relation to the DAS28 before the drug and in the last determination of the DAS28 with that drug, we found statistically significant differences only with the first biological drug, with a p In the case of the following treatment lines, the decrease in DAS 28 does not show statistically significant differences. Moreover, in the evaluation of successive TB, the sample size does not allow us to establish efficacy data with statistical significance. Survival time with the first drug was: the median 14 months (mininum 3 months and max 156 months) The most frequent adverse effects: infections of upper respiratory tract, urinary tract and recurrent cold sores). Reactions at the injection site. We dont have any cases of death. The most frequent reasons for drug suspension in the first line, was secondary failure (40% of cases) followed by a 30% of primary failure and the appearance of adverse effects Discussion TB is an effective and safe option of treatment that should be considered in patients with moderate to severe PAs, who are resistant to classical therapies or who have contraindications to conventional drugs. Although approximately 1/3 of the patients do not respond to these treatments, new trherapies as inhibitor to IL 17 and IR 12–23 pathways are promising and represent another alternative treatment for this patiens.

Background Although there are conflicting data on the subject, it seems that there is a higher incidence of cardiovascular events (CVE) in Rheumatoid Arthritis (RA) compared to population control. Apart from classical cardiovascular risk factors (CV), we must consider the severity of the inflammatory process plays an essential role in accelerated atherosclerosis in this pathology. On the long term security of biological therapies, we find heterogeneous data in different studies and registries. Has observed a decrease in CV risk in RA patients treated with anti-TNF-α agents. Objectives The main aim was to evaluate the CV risk and prevalence of CVD in RA treated with biological teraphies versus RA treated with classics disease modifying drugs (DMARDs). Methods Retrospective cohort study over the CV risk and prevalence of cardiovascular events in RA patients treated with biological therapies. We reviewed a cohort of 260 patients diagnosed with RA (ACR 1987). We recorded sociodemographic variables, classics CV risk factors (smoking history, cholesterol levels, hypertension, diabetes mellitus), immunological profile (presence of RF and/or ACPA), treatment (DMARDs or biological therapy) at the time of the study. The CV risk was measured by the estimated SCORE of atherosclerotic cardiovascular mortality risk in 10 years, for specific values of systolic blood pressure and total cholesterol, according to smoking history, gender and age, calibrated to Spain. Also checked all cardiovascular events occurred since the beginning of RA until time of the study. Results 72% were women, with a current average age of 58.5 years. 48% were receiving biological therapy with or without concomitant DMARDs. Among the classic CV risk factors highlighted: 38% overweight and obesity in 32% of patients, 14% had diabetes mellitus and 39% hypertension; 51% had dyslipidemia and 18% were smokers. Regarding the immune profile had ACPA+61% and 65% FR +. 13% of patients who did not realise biological therapy treatment showed a high Score (5–10) versus 3.7% of patients with biological therapy treatment, this difference was statistically significant. Regarding the prevalence of cardiovascular events we found no difference between groups, 13% and 15% respectively. Conclusions patients treated with biological therapy have lower cardiovascular risk than patients treated with DMARs. WE dont found differences in the prevalence of CVE between groups. Probably the reduction of inflammation with TB has direct relation with cardiovascular risk reduction in patients with RA.

Background Rheumatoid artritis (RA) is a systemic autoimmune disease of unknown and multifactorial aetiology, whoseprevalence is around 1% of the adult population. Anti citrullinated peptide antibodies (ACPA) are the most specific serological markers of RA, with a specificity of 98%–99% in some studies. The presence of autoantibodies such as rheumatoid factor (RF) and ACPA is related to more severe structural damage and joint destruction during disease progression. Objectives To assess whether the presence of ACPA is associated with higher levels of disease activity score (DAS 28) in a sample of patients with RA. Methods We performed a descriptive study of a cohort of patients from Valme Hospital diagnosed with RA. Patients were identified from an electronic database. Demographic data, inmunological profile (presence of RF and/or ACPA),treatment (DMARDs or biological therapy) and disease activity measured by DAS 28 were collected transversely. Results Two hundred and sixty RA patients were included, current average age of 58.5 years, 72% were women, 48% were receiving biological therapy. Regarding serological markers, 61% were ACPA positive, 65% were RF positive and 54.3% were ACPA and RF positive. Mean DAS28 was 2.6 for RF and ACPA negative patients, compared to 2.8 for patients that showed positivity for one or both autoantibodies, without statistically significant difference. With respect to the subgroup of patients receiving biological treatment (n=122), no significant difference of the mean value of DAS28 was seen (regarding to the presence/absence of ACPA): DAS28 2,53 for ACPA positive versus 2.52 for ACPA negative. Conclusions The presence of ACPA in RA patients has been traditionally considered a predictor of radiographic progression and higher clinical activity. But recently, new studies suggest that, although ACPA positivity does maintain relationship with structural damage, there is no association with the severity of clinical activity measured by DAS28. 1 In line with with these results, in our population of RA we found no relationship between the presence of ACPA and/or RF and disease activity, but it should be noted that the present is a cross-sectional study, so further prospective studies will be needed to elucidate this point. Reference M Kaushik R. Anti-Cyclic Citrullinated Peptide Antibodies as a Predictor of Clinical and Radiological Disease Severity in Rheumatoid Arthritis. Curr Rheumatol Rev 2015 Jan 13.

Resumen Objetivo Revisar la evidencia clinica sobre abatacept subcutaneo (sc) y emitir recomendaciones con objeto de aclarar su uso en reumatologia. Metodo Un panel de expertos reumatologos resumio de forma objetiva las pruebas existentes sobre el mecanismo de accion, el modo de uso, la eficacia y la seguridad de abatacept sc y desarrollo un documento sobre el uso de este farmaco en situaciones concretas, previa revision de la bibliografia. Resultados El abatacept sc sustenta su eficacia y seguridad en 7 ensayos clinicos, 3 doble ciego, 3 abiertos y uno mixto, en los que se compara la administracion sc frente a la iv de abatacept, se estudia el posible impacto sobre la inmunogenicidad, el efecto de sustituir la via iv por la sc en pacientes que previamente venian recibiendo abatacept iv, la monoterapia y la no inferioridad frente a adalimumab. No se han encontrado diferencias significativas frente a abatacept iv ni en cuanto a la eficacia ni en cuanto a la seguridad. El desarrollo de abatacept sc ha permitido un estudio complementario al del iv, con lo que el perfil del mismo queda mas definido. Conclusiones Se trata de un documento practico como complemento a la informacion en ficha tecnica. En resumen, el abatacept sc se presenta como un farmaco eficaz y seguro y, por lo tanto, como una alternativa mas para utilizar entre los multiples tratamientos con que cuenta hoy en dia el reumatologo. Ademas, cuenta con la ventaja de ser el unico agente biologico que se puede administrar por via iv y sc, lo cual puede facilitar su uso en determinados pacientes.

Objective To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Results We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. Conclusions We present the SER recommendations for the use of biological therapies in patients with SLE.

Objetivo Elaborar unas recomendaciones que sirvan de referencia a los reumatologos y otros profesionales implicados en el tratamiento del lupus eritematoso sistemico (LES) que vayan a utilizar o consideren la utilizacion de terapias biologicas en su manejo. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales y basadas en revisiones sistematicas. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Resultados Se realizan recomendaciones sobre el uso de belimumab, actualmente unica terapia biologica con aprobacion para el tratamiento del LES, y otras terapias biologicas sin indicacion aprobada en LES. El objetivo del tratamiento es la respuesta clinica completa, entendida como la ausencia de actividad clinica percibida o constatable. Se matiza el uso de terapias biologicas en LES y cual debe ser la evaluacion previa y la vigilancia del paciente que recibe estos farmacos. Conclusiones Se presentan las recomendaciones SER sobre el uso de terapias biologicas en el LES.

Resumen Objetivo Revisar la evidencia clinica sobre abatacept y emitir recomendaciones con objeto de aclarar su uso en Reumatologia. Metodo Un panel de expertos reumatologos resumio de forma objetiva las pruebas existentes sobre el mecanismo de accion, modo de uso, eficacia y seguridad de abatacept y emitio recomendaciones de uso en situaciones concretas, previa revision de la bibliografia. Se establecio el nivel de evidencia de las pruebas y el grado de apoyo de dichos datos a las recomendaciones emitidas. Resultados El documento presenta 21 enunciados resumen de la evidencia encontrada o recomendaciones sobre abatacept (14 enunciados y 9 recomendaciones). El nivel de evidencia es superior a 2b segun la escala de Oxford del Centro de Medicina Basada en la Evidencia en 14 ocasiones. El grado de apoyo de las recomendaciones es A en 2 recomendaciones, C en una y D en el resto. Se considero importante realizar recomendaciones precisamente en los aspectos con menor grado de evidencia. Conclusiones Se trata de un documento practico como complemento a la informacion en ficha tecnica.

Resumen Objetivo Dado el creciente uso de las terapias biologicas en distintas enfermedades reumatologicas, y la importancia de la gestion de riesgo de las mismas, desde la Sociedad Espanola de Reumatologia (SER) se ha impulsado el desarrollo de recomendaciones basadas en la mejor evidencia posible. Estas deben de servir de referencia para reumatologos e implicados en el tratamiento de pacientes en tratamiento o en los que se quiere indicar la terapia biologica independientemente de su enfermedad de base. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Se utilizo toda la informacion de consensos y guias de practica clinica previas. Resultados Se realizan recomendaciones sobre la gestion del riesgo del uso de las terapias biologicas en pacientes con enfermedades reumatica. Incluyen la gestion del riesgo de la indicacion, gestion del riesgo antes de iniciar el tratamiento, gestion del riesgo durante el seguimiento, actitud ante acontecimientos adversos, y actitud en situaciones especiales. Conclusiones Se presentan las recomendaciones SER sobre la gestion del riesgo del tratamiento con terapias biologicas.

Introduction Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use. Objective To establish recommendations that facilitate the use of rituximab in common clinical practice. Methods In a first Delphi round, 9 expert rheumatologists got together to develop questions on those subjects generating most doubts on the efficacy and safety of the drug. These were adapted to perform a systematic review of the evidence, which was presented in a second meeting. Nominal groups were formed to respond to each question and give a recommendation. These recommendations were presented in a second Delphi round to a larger group of experts in rheumatology. Once again recommendations were discussed, modified and voted upon. Once approved, a vote on the degree of agreement for each recommendation was carried out. Results Seventeen recommendations were established, 10 regarding efficacy and 7 safety. All of the efficacy recommendations except 3 presented a good or moderate degree of evidence. Among the safety recommendations, 3 had a good or moderate degree of evidence while in the rest it was indirect, scarce or non-existent and a product of expert recommendation. The degree of agreement between experts was elevated for most of the recommendations. Conclusions These recommendations attempt to clear doubts on the use of rituximab and establish guidelines for its use in daily practice. Efficacy recommendations have a high degree of evidence, allowing the clinician to be guided in therapeutic decisions. Safety recommendations have a lower degree of evidence.

Introduction: Rituximab has been employed successfully for the treatment of Rheumatoid Arthritis (RA). However, its particular mechanism of action, as well as a lack of concrete guidelines for its management have generated doubts on its use.

Systemic lupus erythematosus is an autoimmune disease that may involve the function of organs and reduce the survival of patients. Advances in the diagnosis and treatment have improved the short-term prognosis.However, most therapeutic improvements come from progress in other areas of medicine and only in recent years is this trend changing. Unfortunately, the development of new drugs for lupus is facing specific difficulties and the development of rituximab in lupus has been stopped despite good results in the observational studies. This review examines some of the aspects that influence these difficulties from the perspective of the LESIMAB database.

Objetivos El objetivo de este estudio ha sido comparar la eficiencia de utilizar el metotrexato subcutaneo (Metoject®) con respecto al metotrexato oral en el manejo de pacientes con AR en Espana. Metodos Se ha realizado un analisis coste-efectividad/utilidad del tratamiento de la AR temprana utilizando un modelo de Markov. El modelo ha permitido estimar la efectividad a largo plazo del tratamiento de la AR en funcion de los datos de la literatura y de la opinion de expertos y combinarlo con informacion de los costes en Espana. El analisis se ha realizado desde la perspectiva del Sistema Nacional de Salud, utilizando un horizonte temporal de 5 anos y de toda la vida del paciente. Todos los costes se expresaron en euros del ano 2009 y se ha utilizado una tasa de descuento del 3%. Resultados La razon de coste (solo costes farmacologicos) por ano de vida ajustado por calidad (AVAC) ganado con Metoject® fue de 25.173�35.807� a los 5 anos y de 19.056�25.351� para toda la vida. Al tener en cuenta los costes directos de la AR se observo que el coste-efectividad a los 5 anos fue de 29.682�42.175�/AVAC ganado y para toda la vida fue de 22.514�29.848�/AVAC ganado. Conclusiones Los costes adicionales de Metoject® respecto a metotrexato oral se verian compensados por su mejora en efectividad, expresada en terminos de AVAC, revelando que Metoject® podria ser un tratamiento costeefectivo para la AR en el Sistema Nacional de Salud segun el umbral asumido en Espana.

Objectives The aim of this study was to compare the clinical and economic consequences of using subcutaneous methotrexate (Metoject®) with respect to oral methotrexate in the management of rheumatoid arthritis (RA) in Spain. Methods A cost-effectiveness analysis was performed to compare early treatment of RA using a Markov model. The model allowed us to estimate long term efficacy of RA treatment based on data from the literature and expert opinion, and to combine this data with costs of managing RA in Spain. The perspective of the study was from the National Health System point of view, using a time horizon of 5 years and patient lifetime. All costs were expressed in 2009 euros and a 3% discount rate was applied. Results The cost (only pharmacologic costs) per quality-adjusted life year (QALY) gained with Metoject® went from 25,173 to 35,807 € at 5 years and from 19,056 to 25,351 € for patient lifetime. When direct costs in RA treatment were considered, it was observed that cost-effectiveness at 5 years went from 29,682 to 42,175 €/QALY gained, and for patient lifetime from 22,514 to 29,848 €/QALY gained. Conclusions Additional costs of Metoject® with respect to oral methotrexate would be offset by their improved effectiveness, expressed in QALY, showing that Metoject® could be a cost-effective treatment option for RA in the Spanish Health System assuming a spanish threshold.

Anti-TNF drugs have represented a great advancement in the treatment of rheumatoid arthritis since their introduction in the late 1990s. The development of these products has been very similar for etanercept, infliximab and adalimumab, the 3 approved TNF blockers for the treatment of RA. The first studies centered their attention on patients with active disease and refractory to several disease modifying treatments, finding very significant differences when compared to placebo or methotrexate in the ACR improvement scores. Trials in patients who had not been previously treated with methotrexate show less differences between anti-TNF and methotrexate, but becomes more significant when the two drugs are used combined. In this manuscript we analyze the results of the registry of anti-TNF studies with regard to other improvement indexes such as quality of life, reduction in cardiovascular risk, maintained efficacy through time and progression of joint erosions. We also contemplate the possibility of using lower doses than those authorized for rheumatoid arthritis and analyze factors related to a poor prognosis in patients refractory to methotrexate, which is currently the indication for the use of anti-TNF in RA accordiong to the SER consensus.

Las protesis articulares constituyen uno de los mayores avances de la medicina en el tratamiento de los pacientes con enfermedad osteoarticular. Las infecciones del material protesico, aunque poco frecuentes (un 1-3% segun series y tipo de protesis), constituyen una de las mayores complicaciones de esta cirugia y un reto diagnostico para el medico. El concepto de infeccion protesica incluye colonizacion por germenes del material periprotesico que ademas lleva a manifestaciones clinicas. Existen diversas clasificaciones de las infecciones protesicas, la mayoria de ellas basadas en la forma de presentacion clinica, que en gran parte depende del germen implicado en la etiologia de la infeccion. En este sentido, las formas tardias, originadas generalmente por germenes poco virulentos (el estafilococo plasmacoagulasa negativo es el mas frecuente), son los casos mas dificiles de diagnosticar. La sospecha diagnostica debe establecerse en funcion de las manifestaciones clinicas y de una serie de signos clinicos acompanantes. En este sentido, en ausencia de reumatismo inflamatorio de base, la persistente elevacion de la PCR (suele normalizarse 1-2 semanas tras la cirugia) o la presencia de un liquido articular inflamatorio (recuentos > 1.700 celulas/ml y en especial con predominio de polimorfonucleares > 68%) son signos para la sospecha diagnostica de infeccion bacteriana. El diagnostico definitivo se establece por el aislamiento del germen en cultivo; la biopsia del material periprotesico y su estudio anatomopatologico y cultivo permiten establecer el diagnostico de seguridad en un 80-90% de los casos.

Objectives. To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. Methods. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Results. Three damage clusters were identified. Cluster (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 10096 in clusters 2 and 3. P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 0.096 of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. Conclusion. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ?4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ?1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (?10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect. Spanish Foundation of Rheumatology. FIS/ISCIII (grant number PI11/02857). Dr. Pego-Reigosa is supported by Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012–2013.1).

Calciphylaxis is a potentially lethal syndrome reported mainly in patients with ESRD on hemodialysis. Etiopathogenesis remains unclear and there is much controversy regarding optimal diagnostic and therapeutic approach. Penile necrosis as a disease presentation is extremely rare. We report two clinical cases treated in our center and perform an evidence review.Clinical data was obtained from both patients and an evidence review was performed on PubMed under the criteria "penile necrosis" and "Calciphylaxis".Both patients underwent partial penectomy due to severe penile necrosis. After surgery both patients received treatment with sodium thiosulfate (STS) 20mg in every hemodialysis session. Both patients showed stabilization of necrotic lesions.The same way that biopsying the ischemic lesions produced by Calciphylaxis is discussed and even misadvised, the role of aggressive surgery as first line therapy might be uncertain specially with the raising of new specific drugs such as sodium thiosulfate (STS) that have shown efficacy stopping disease progression.