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To study retention of biologic disease-modifying anti-rheumatic drugs (bDMARDs) or apremilast and potential predictors of lack of response in patients with psoriatic arthritis (PsA). A single-center retrospective analysis of PsA patients who received ≥ 1 bDMARD or apremilast during 2000–2018. The main endpoint was lack of response (primary or secondary failure). Analyses included retention of DMARDs (Kaplan–Meier curves) and potential predictors of lack of response (bivariate and multivariate logistic regression models). A total of 159 patients with PsA received up to 8 DMARDs: etanercept (34%), adalimumab (30%), infliximab (9%), golimumab (9%), apremilast (7%), ustekinumab (5%), certolizumab (4%), and secukinumab (2%). Therapy was discontinued in 96 cases (60%), mainly owing to secondary failure (37%), followed by primary failure (25%) and adverse effects (24%). Retention was analyzed based on 313 units of analysis. Duration of follow-up was 846.1 treatment-years (maximum 14.8 years, median 2.75 years). A total of 172 DMARDs were discontinued. The probability of continuing the initial treatment was 37% at 5 years, 22% at 10 years, and 12% at 14 years. The longest medium retention time was observed for infliximab (6.2 years) and etanercept (4.5 years). Predictors of lack of response included male sex, number of swollen joints, and, especially, depression (OR = 35.2). The sensitivity and specificity of the model were 86.4% and 85.7%, respectively, with a coefficient of determination (R2) of 45.6 (ROC, 0.912). Rates of discontinuation due to primary and secondary failure are high in PsA. Retention is better for anti-TNF agents than for other agents.

Objective SLE can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in >50% of SLE patients. To describe the GI manifestations of SLE in the RELESSER (Registry of SLE Patients of the Spanish Society of Rheumatology) cohort and to determine whether these are associated with a more severe disease, damage accrual and a worse prognosis. Methods We conducted a nationwide, retrospective, multicentre, cross-sectional cohort study of 3658 SLE patients who fulfil ≥4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease. Results From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI (SLICC Damage Index). The presence of oral ulcers reduced the risk of developing damage in 33% of patients. Conclusion Having GI damage is associated with a worse prognosis. Patients on a high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

Introduction Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus(SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Materials and methods Patients from the RELESSER-T registry were included. RELESSER-T is a Spanish multicenter, hospital-based, retrospective, SLE registry. Results We included 2398 SLE patients, 1372 of whom were positive for aPL. Overall 1026 patients were classified as SLE, 555 as SLE-APS and817 as SLE-aPL. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than those with SLE-aPL and SLE ( p Conclusions SLE-APS patients exhibited more severe clinical profiles with higher frequencies of major organ involvement, greater damage accrual and higher mortality than SLE-aPL and SLE patients.

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 OBJECTIVE: Estimate the frequency of the association of SLE with other autoimmune diseases in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigate the main risk factors for polyatoimmunity. Methods Design: RELESSER is a nationwide multicentre, hospital-based registry of SLE patients. This is a cross-sectional study. Patients: Unselected consecutive adult patients with SLE, classified according to the American College of Rheumatology (ACR) 1997 criteria. All patients had been attended upon and followed at Spanish rheumatology departments. The first patient was enrolled in October 2011 and the last in August 2012. Main outcome: Polyautoimmunity was defined as patients who fulfilled criteria for SLE and other autoimmune disease: (1) autoimmune thyroiditis (alteration of thyroid function with the presence of anti-thyroid autoantibodies), (2) other connective tissue disease (rheumatoid arthritis, systemic sclerosis or inflammatory myopathy) and (3) mixed connective tissue disease. Multiple autoimmune syndrome (MAS) was defined as patients who meet SLE criteria and at least two other autoimmune diseases. Other variables: Demographic and clinical variables, Sjogren’s syndrome, antiphospholipid syndrome and family history of autoimmune systemic disease were collected. Statistical analysis: Descriptive, Chi-square test and ANOVA or Kruskal-Wallis for comparison between groups of patients. Multiple logistic regression analysis was performed to investigate the possible risk factors for polyautoimmunity in patients with SLE. Results From all patients included in the registry, 3679 (91.4%) patients met 4 or more SLE criteria. Of these, 501 (13.6%) patients had Polyautoimmunity. The characteristics of this group are showed in table 1. The most frequent polyautoimmunity types associated with SLE were (in descending order over the total cohort of patients with SLE): autoimmune thyroiditis (7.5%), other connective tissue disorders (4.4%) and mixed connective tissue disease (2.7%). The percentage of patients a family history of SLE was 12.4%. Multiple autoimmune syndrome was observed in 10.2% of patients with Polyautoimmunity. The multivariate analysis identified age (odds ratio [95% confidence interval], 1.01 [1.00–1.02]), sex (3.00 [1.48–6.04]), Raynaud’s phenomenon (1.79 [1.34–2.39]), pulmonary fibrosis (2.88 [1.32–6.30]), Ro-La autoantibodies (1.68 [1.20–2.36]), antiRNP (1.79 [1.32–2.42]) and treatment with methotrexate (1.54 [1.08–2.18]) or with antimalarials (0.57 [0.41–0.78]) as factors associated with polyautoimmunity. Conclusions SLE patients frequently associate other autoimmune diseases, detecting poliautoimmunity in 14%, MAS in 2%, family history of SLE in 12.4% and others such as Sjogren’s syndrome and secondary SAF in 12.8% and 12.7% respectively. More studies are needed to better understand the increase of polyautoimmunity that seems to be observed in SLE. Funding Source(s): None

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus (SLE) patients. Our aim was to investigate the differences between SLE patients according to the presence of aPL and/or clinical antiphospholipid syndrome (APS). Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results We included 3651 SLE patients and 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin antibodies, 27.3% showed positivity for anti b2glycoprotein I and 24% for lupus anticoagulant). Overall 2283 patients were classified as SLE no aPL, 528 as SLE-APS and 840 as SLE-aPL. Demographic data, clinical and laboratory features in the different groups are showed in table 1. Regarding cardiovascular risk factors, SLE-APS patients had higher rates of hypertension, dyslipidemia and diabetes than SLE-aPL and SLE no aPL patients (p 0.5 grs), urinary cell casts, seizures and psychosis (p0.001). Overall, SLE-APS patients showed a lower rate of cutaneous manifestations and higher rates of neuropsychiatric, cardiac, pulmonary, renal, joint and ophthalmological manifestations (table 1). In accordance with a more severe clinical profile, higher frequency of anti-DNA antibodies and hypocomplementemia were observed in the SLE-APS group (p Conclusions SLE-APS patients show a more severe clinical profile with higher frequency of major organ involvement and more damage accrual than SLE-aPL and SLE no APL. Funding Source(s): None

Background Antiphospholipid antibodies (aPL) have been associated with organ damage and certain features in systemic lupus erythematosus (SLE) patients. Our aim is to investigate the association between the different aPL and SLE manifestations as well as to elucidate the influence of the load of antibodies. Methods Patients from the RELESSER-T registry were included. RELESSER-T is a multicenter, hospital-based registry, with retrospective cross-sectional collection of data from a large representative sample of adult non-selected patients with SLE attending Spanish rheumatology services from the public national health system. Results Out of a total of 3651 SLE patients, 1368 were positive for aPL (44.9% of patients were positive for anticardiolipin (aCL) antibodies, 27.3% for anti b2glycoprotein I (aB2GPI) and 24% for lupus anticoagulant (LA)). Regarding the load of antibodies, 20.6%, 12.1% and 4.8% were positive for one, two and three antibodies, respectively. The association between the different aPL, the number of positive antibodies and antiphospholipid syndrome related manifestations is showed in table 1. Overall, all types of aPL were associated with classic APS manifestations, although LA, IgG isotypes, and patients with more than one aPL display a higher risk to develop clinical APS. Regarding specific lupus manifestations, all aPL types showed a negative association with cutaneous manifestations, and was also significantly associated with the load of autoantibodies (p Conclusions The present study in a large SLE cohort confirm than there is a hierarchy for aPL and the risk of APS and lupus manifestations. aCL, and especially LA, confer a higher risk for major organ involvement in SLE patients. IgG isotypes and the load of aPL antibodies confer a higher risk for clinical APS and major lupus manifestations. Funding Source(s): None

Objective: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (6 months); (c) serious infections (with or without); (d) < 15 vs. >15 mg/day at TCZ onset. Results: 134 patients; mean age, 73.0 +/- 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. Conclusion: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials. (C) 2019 Elsevier Inc. All rights reserved.

ObjectivePsoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA.MethodsWe performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case–control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA.ResultsWe identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDRConclusionThese findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

a b s t r a c t Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that occurs in immunosuppressed patients or those with discontinuity of defense barriers. There are only 15 cases described in the literature. The diagnosis is based on clinical features and the isolation of a microorganism in synovial fluid or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or scintigraphy) may be useful. Antibiotic treatment is the same as in septic arthritis in other locations. Staphylococcus aureus is the microorganism most frequently isolated. Our objective was to describe the clinical features, treatment and outcome of patients diagnosed with septic arthritis of the acromioclavicular joint at a Rheumatology Department. We developed a study with a retrospective design (1989–2012). The medical records of patients with septic arthritis were reviewed (101 patients). Those involving the acromioclavicular joint were selected (6 patients; 6%).

Objective Polyarticular septic arthritis accounts for 15% of all septic arthritis, but there are few references in the literature. We describe characteristics of patients with polyarticular septic arthritis in a rheumatology service. Patients and method Retrospective analysis of patients with septic arthritis involving more than one joint. Only patients with positive culture of synovial fluid were included. Clinical, analytical, and radiological variables are reviewed. Results Nineteen patients (14 male) had a polyarticular infection. Mean age was 55 years. Mean time from onset to diagnosis was 6 days. The knee was the most commonly involved joint, followed by ankle. The mean number of joints involved per patient was 3. Risk factors included diabetes, chronic renal, or hepatic disease, gout, and rheumatoid arthritis. Most commonly isolated agents were S aureus (47%) and S agalactiae (21%). Blood cultures were positive in 52.6% and 15.8% had septic shock. Scintygraphic bone scan showed a polyarticular uptake. Mean duration of antibiotic therapy was 46 (27) days. Clinical outcome was good in 52.6%, complicated in 26%, and mortality rate was 15.8% (3 cases). Joint debridement was performed in 21%. Conclusions Multiple joint involvement does not exclude the diagnosis of septic arthritis. Inflammatory arthritis is an important risk factor. S aureus in the main infectious agent. The morbidity and mortality of this condition are important, so we need to maintain a high index of suspicion for the condition.

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and redissolve on rewarming. These immunoglobulins can form immune complexes that precipitate in blood vessels, activate complement and cause cryoglobulinemic vasculitis. Cryoglobulinemia is classified intro three serological subsets; of these, type II, or mixed cryoglobulinemia, is associated with hepatitis C virus (HCV) infection in more than 80% of cases. The discovery of this association has changed therapeutic strategies in cryoglobulinemic vasculitis, which is now considered an extrahepatic manifestation of HCV infection. Therefore, the main therapeutic approach currently consists of antiviral therapies such as interferon or ribavirin. In patients refractory to these treatments, new agents such as rituximab, infliximab and mycophenolate mofetil are being used. The development of an effective vaccine against HCV would drastically reduce the number of cases of this form of vasculitis.

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).

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis. RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis. From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2-66.1], and SLE duration of 212.0 months [120.8-289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02-1.04]), hypertension (1.71 [1.20-2.44]), smoking (1.48 [1.06-2.07]), diabetes (2.2 [1.32-3.74]), dyslipidemia (2.18 [1.54-3.09]), neurolupus (2.42 [1.56-3.75]), valvulopathy (2.44 [1.34-4.26]), serositis (1.54 [1.09-2.18]), antiphospholipid antibodies (1.57 [1.13-2.17]), low complement (1.81 [1.12-2.93]), and azathioprine (1.47 [1.04-2.07]) as risk factors for CV events. We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows-for the first time-an association between diabetes and CV events in SLE patients.

a b s t r a c t Introduction: Churg-Strauss Syndrome (CSS) is a necrotizing vasculitis affecting small to medium-sized vessels, characterized by lung involvement, asthma and peripheral blood eosinophilia, and pathologically by the presence of granulomas and eosinophilic infiltrates. Objectives: This report analizes the characteristics of 9 patients with SCS diagnosed in an university referral center. Patients and methods: Retrospective study. Between 1984 and 2007 nine patients with SCS were diagnosed in our center. Epidemiological, clinical, laboratory test as well as pathologic studies and treatment required were retrospectively analyzed. Results: Nine patients (7 males). The mean age at the time of diagnosis was 51 years (range 23-76 years). Eight of these patients had history of asthma. The more frequent organs involved were the skin (66%), musculoesqueletical system (66%), peripheral nervous system (55%) and the lung (55%). All patients presented peripheral eosinophilia. ANCA positivity was demonstrated in 6 patients (66%), most of the patients with the p-ANCA pattern. All patients were treated with corticosteroids, and in 8 immunosupressant treatment was required, mainly cyclophosphamide. Conclusions: In this report, 9 patients with SCS are presented. Clinical characteristics are similar with the observed in other reports. We observed a major positivity of ANCA. Most of the patients were treated with corticosteroids and inmunosupresants, but the treatment should be tailored depending on the involvement of the patient.

Cardiac involvement in vasculitis syndromes is uncommon. We describe a 50-year-old male who presented with progressive dyspnea and myalgies. Echocardiogram revealed significant thickening of aortic root, aortic cusps, and anterior mitral valve leaflet, with severe aortic regurgitation that required aortic valve replacement. Furthermore, this patient suffered progressive atrioventricular block that needed implantation of a pacemaker. The study performed disclosed the presence of necrotizing vasculitis positive for perinuclear antineutrophil cytoplasmic antibody. (ECHOCARDIOGRAPHY, Volume 20, October 2003)