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Sjogren's syndrome is an autoimmune disease that involves exocrine glands. The most characteristic symptoms consist of the sicca syndrome (including xerostomia and dry eye - xerophtalmia), but can involve multiple organs. The extraglandular involvement determines the prognosis. It is typically associated with the presence of antinuclear antibodies, including Ro-60 antibodies. Pulmonary involvement appears as bronchiectasis and/or interstitial pneumonia. Considering its high prevalence, it must be ruled out in all patients with respiratory symptoms by performing pulmonary function tests and high-resolution computed tomography of the chest. Evaluation can be completed with a transbronchial biopsy if diagnostic doubts persist. Treatment includes steroid therapy, inmunosupressive or antifibrotic drugs, or biological therapy. In selected cases pulmonary transplantation must be considered.

Objective To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren’s Syndrome (pSS) and non-Sjögren Sicca syndrome. Methods Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. Results The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value Conclusion Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.

Summary Long-term observation of patients with ANCA-associated vasculitis (AAV) allows the identification of different longitudinal patterns of ANCA levels during follow-up. This study aimed to characterize these patterns and to determine their prognostic significance. All ANCA determinations performed in two university hospitals during a 2-year period were retrospectively reviewed. Patients were included in the analysis if they had high titers of anti-myeloperoxidase (anti-MPO) or anti-proteinase 3 (anti-PR3) antibodies at least once, ≥ 5 serial ANCA determinations and AAV diagnosed by biopsy or American College of Rheumatology (ACR) classification criteria. Patients’ time–course ANCA patterns were classified as monophasic, remitting, recurrent or persistent. Associations between ANCA patterns and prognostic variables (relapse rate and renal outcome) were analysed by univariate and multivariate statistics. A total of 99 patients [55 with microscopic polyangiitis (MPA), 36 with granulomatosis with polyangiitis (GPA) and eight with eosinophilic granulomatosis with polyangiitis (EGPA)] were included. Median follow-up was 9 years. Among patients diagnosed with MPA or GPA, recurrent or persistent ANCA patterns were associated with a higher risk of clinical relapse [hazard ratio (HR) = 3·7, 95% confidence interval (CI) = 1·5–9·1 and HR = 2·9, 95% CI = 1·1–8·0, respectively], independently of clinical diagnosis or ANCA specificity. In patients with anti-MPO antibodies, the recurrent ANCA pattern was associated with worsening renal function [odds ratio (OR) = 5·7, 95% CI = 1·2–26·0]. Recurrent or persistent ANCA patterns are associated with a higher risk of clinical relapse. A recurrent ANCA pattern was associated with worsening renal function in anti-MPO-associated vasculitis.

Objective To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P 65 years, P Conclusion The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Objective: To compare the accuracy of the Birmingham Vasculitis Activity Score (BVAS), version 3, and the Five Factor Score (FFS), version 1996 and version 2009, to assess survival in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Methods: A total of 550 patients with AAV (41.1% with granulomatosis with polyangiitis, 37.3% with microscopic polyangiitis, and 21.6% with eosinophilic granulomatosis with polyangiitis), diagnosed between 1990 and 2016, were analyzed. Receiver operating characteristic (ROC) curves and multivariable Cox analysis were used to assess the relationships between the outcome and the different scores. Results: Overall mortality was 33.1%. The mean ± SD BVAS at diagnosis was 17.96 ± 7.82 and was significantly higher in nonsurvivors than in survivors (mean ± SD 20.0 ± 8.14 versus 16.95 ± 7.47, respectively; P < 0.001). The mean ± SD 1996 FFS and 2009 FFS were 0.81 ± 0.94 and 1.47 ± 1.16, respectively, and were significantly higher in nonsurvivors than in survivors (mean ± SD 1996 FFS 1.17 ± 1.07 versus 0.63 ± 0.81 [P < 0.001] and 2009 FFS 2.13 ± 1.09 versus 1.15 ± 1.05 [P < 0.001], respectively). Mortality rates increased according to the different 1996 FFS and 2009 FFS categories. In multivariate analysis, BVAS, 1996 FFS, and 2009 FFS were significantly related to death (P = 0.007, P = 0.020, P < 0.001, respectively), but the stronger predictor was the 2009 FFS (hazard ratio 2.9 [95% confidence interval 2.4–3.6]). When the accuracy of BVAS, 1996 FFS, and 2009 FFS to predict survival was compared in the global cohort, ROC analysis yielded area under the curve values of 0.60, 0.65, and 0.74, respectively, indicating that 2009 FFS had the best performance. Similar results were obtained when comparing these scores in patients diagnosed before and after 2001 and when assessing the 1-year, 5-year, and long-term mortality. Correlation among BVAS and 1996 FFS was modest (r = 0.49; P < 0.001) but higher than between BVAS and the 2009 FFS (r = 0.28; P < 0.001). Conclusion: BVAS and FFS are useful to predict survival in AAV, but the 2009 FFS has the best prognostic accuracy at any point of the disease course.

To analyse the risk of ischaemic events in patients with newly diagnosed giant cell arteritis (GCA) according to PET/CT findings. PET/CT was performed during the first 10 days of steroid therapy. Clinical manifestations at diagnosis, and physical examination and PET/CT findings were recorded and compared according to the presence or absence of ischaemic symptoms at disease onset. Analysed territories included the ascending aorta, aortic arch, descending aorta, abdominal aorta, carotid arteries, brachiocephalic trunk, vertebral arteries, subclavian arteries and axillary arteries. The study group comprised 30 patients with a median age of 80.8 years. Of these patients, 21 (70%) reported ischaemic symptoms at diagnosis, and 13 (43.3%) had permanent visual loss. Of the 30 patients, 77.8% showed large vessel vasculitis (including aortic and vertebral artery involvement) on PET/CT, and 60% had isolated involvement of the vertebral territory. Vertebral arteries were more frequently involved in patients with ischaemic symptoms (OR 5.0, 95% CI 0.99–24.86, p = 0.051). The presence of vertebral artery involvement in the absence of aortic involvement was associated with the presence of ischaemic manifestations (Fisher’s exact test, p = 0.001). The presence of aortitis was found to protect against the development of permanent visual loss (OR 19.0, 95% CI 2.79–127.97, p = 0.001). Our findings suggest an association between the vascular pattern on PET/CT at the time of GCA diagnosis and the risk of ischaemic events.

Arteritis de Takayasu; Tocilizumab; Teràpia biològica Arteritis de Takayasu; Tocilizumab; Terapia biológica Takayasu’s arteritis; Tocilizumab; Biological therapy Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu’s arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5–50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0–31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5–50.0) to 5.0 (0.0–5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0–14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0–46.0) versus 45.0 (38.0–57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0–38.0) versus 6.0 (1.0–23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7–5.6) versus 1.3 (0.3–3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain). However, this research did not receive any specific grant from funding agencies in the commercial or not-for-profit sectors.

Objective To define the pattern of cardiac involvement in eosinophilic granulomatosis and polyangiitis (EGPA) and propose an algorithm for heart disease screening. Methods This was a retrospective study of EGPA patients attending a specialized vasculitis clinic (1989–2016). Clinical characteristics and cardiovascular evaluation (CE) results (serum troponin, ECG, echocardiography and cardiac magnetic resonance) were collected and compared according to symptoms and inflammatory cardiac disease (ICD). Results A total of 131 EGPA patients were included, of whom 96 (73%) had undergone CE. The median (interquartile range) age was 50 (38–58) years and 36% showed ANCA+. Asthma preceded diagnosis by a median of 97 (36–240) months. Among the 96 patients who underwent CE, 43% were symptomatic, with dyspnea (47%) and chest pain (29%) being the predominant symptoms. In asymptomatic patients, CE reported abnormalities in 45% of cases, with a subsequent earlier diagnosis (4 vs 11 months). Overall, 27 patients had EGPA-related ICD (EGPA-rICD) that was already present at diagnosis in 20 cases, preceded it in 2 cases and developed later in 5 cases. EGPA-rICD patients were younger (46 vs 50 years; P = 0.04), had more frequently abnormal ECG (30.8 vs 2.1%; P Conclusion In our study, 45% of asymptomatic patients had an abnormal baseline cardiac evaluation, which allowed an earlier diagnosis of cardiac disease. We recommend prompt cardiac screening in all EGPA patients, instead of a symptoms-guided algorithm.

Amyloidosis comprises a group of heterogeneous conditions. To ascertain the burden of disease is important because it can determine the treatment as well as the evolution of the disease. Recent reports have shown good results in diagnosing cardiac amyloidosis using 18F-florbetapir. We hypothesize that combining whole body PET/CT with 18F-Florbetapir can be useful to characterize the burden of the disease. We included 25 patients, 13 of them with different types of amyloidosis, and 12 with Alzheimer's disease as controls. Target-to-background ratio was computed for multiple organ using maximum standardized uptake values. Organ involvement was described (standardized techniques versus PET) according to different kinds of amyloidosis showing promising results in AA and AL types. Heart involvement showed poorer results when compared to tongue, lung or thyroid gland. Multiple organ involvement in patients previously labelled as having negative organ affectation could be identified. This is the first study to evaluate the utility of 18F-florbetapir in the assessment of the global extension of disease. Our results show that this technique is useful for its diagnosis.

Background Tocilizumab (TCZ) has been approved for the treatment of Giant Cell Arteritis (GCA). It showed to be effective to induce remission, prevent relapses and decrease the cumulative prednisone dose. However, the glucocorticoids are the mainstay in the acute treatment of GCA. Objectives Our aim was to compare the efficacy and safety of the initial dose of prednisone at the onset of TCZ treatment. Methods Retrospective, multicenter study on 134 patients with GCA in treatment with TCZ. We compared two subgroups of patients according to the initial dose of prednisone at TCZ onset. Clinical efficacy, analytical improvement and safety was studied. Results We studied 134 patients (101 w/33 m) and made a comparative study between 2 groups: a) TCZ and ≤ 15 mg of prednisone; 68 (50.7%) cases, and b) TCZ and > 15 mg of prednisone, 66 (49,3%) patients. It is summarized in TABLE 1. It was no statistical significance according to age, sex and evolution time of disease. In the group receiving > 15 mg of prednisone, the patients presented more visual involvement (p 15 mg of prednisone (p=0.001 and p=0.006, respectively). TABLE 2 summarizes the infections of our patients. Conclusion According with our results, we can conclude that TCZ is equally effective; in terms of prolonged remission and relapses, with doses ≤ 15 mg of prednisone at treatment onset. Being the most important data, the higher risk to develop adverse effects, as well as infections with higher doses of prednisone. References [1] Proven A. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum. 2003; 49:703-8. [2] Calderon-Goercke M. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Jan 5. pii: S0049-0172(18)30571-7. doi: 10.1016/j.semarthrit.2019.01.003. [Epub ahead of print] Disclosure of Interests Monica Calderon-Goercke: None declared, J. Loricera: None declared, D. Prieto-Pena: None declared, Vicente Aldasoro: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ignacio Villa-Blanco: None declared, Alicia Humbria: None declared, Clara Moriano: None declared, Susana Romero-Yuste: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Catalina Gomez-Arango: None declared, Eva Perez-Pampin: None declared, Rafael Melero: None declared, Elena Becerra-Fernandez: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, Maria Alvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernandez-Lopez: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Eva Galindez: None declared, Beatriz Arca: None declared, Roser Solans-Laque: None declared, Arantxa Conesa: None declared, Cristina Hidalgo: None declared, Carlos Vazquez: None declared, Jose Andres Roman-Ivorra: None declared, Pau Lluch: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., 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, Eugenio de Miguel: None declared, Carmen Torres-Martin: None declared, Juan Carlos Nieto: None declared, Carmen Ordas-Calvo: None declared, Eva Salgado-Perez: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Saenz de Miera: None declared, Nagore Fernandez-Llanio: None declared, Antonio Garcia: None declared, Carmen Larena: None declared, Natalia Palmou-Fontana: None declared, Vanesa Calvo-Rio: None declared, Carmen Gonzalez-Vela: None declared, Alfonso Corrales: None declared, Maria Varela-Garcia: None declared, Elena Aurrecoechea: None declared, Raquel Dos-Santos: None declared, Angel Garcia-Manzanares: None declared, Norberto Ortego: None declared, Sabela Fernandez: None declared, Francisco Ortiz-Sanjuan: None declared, Montserrat Corteguera: None declared, J. Luis Hernandez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background In Giant Cell Arteritis (GCA) two dominant cytokine clusters have been linked to disease activity, IL-6 – IL-17 axis (Th17) and IL-12 – IFN γ axis (Th1). The first one related to systemic symptoms and the second route responsible for ischemic symptoms. Tocilizumab (TCZ) performs its effect mainly by inhibiting Th17 axis and terminally Th1 route. Objectives Our aim was to evaluate the effect of TCZ on ischemic and systemic symptoms throughout the follow-up. Methods Retrospective, multicenter study of 134 patients diagnosed of GCA on treatment with TCZ. We evaluate the efficacy of TCZ by improving ischemic (visual involvement, headache, jaw claudication) and systemic symptoms (fever, constitutional syndrome, polymyalgia rheumatica (PMR)). Results We evaluated 134 patients (101 w/33 m) and its main symptoms at TCZ onset, TABLE. 73 (54.5%) patients presented PMR followed by headache in 70 (52.2%) cases, constitutional syndrome in 31 (23.1%) and visual involvement in 28 (20.9%) patients. After one month of treatment there was an important clinical improvement, persisting in 13,6% of patients PMR, 10.6% headache and 10.6% visual involvement. Throughout the follow-up, the improvement of ischemic symptoms was slower. At month 12, in 5.6% (4) of patients persisted with visual impairment, and 2.8% (2) patients presented headache and constitutional syndrome. However, the analytical improvement was statistically significant from the first month and sustained during follow-up. Conclusion According to the results of our study, we can conclude that in clinical practice, ischemic symptoms take longer to improve than systemic symptoms; being visual affectation the most frequent symptom after 12 months of follow-up. References [1] Soriano A, Muratore F, Pipitone N, Boiardi L, Cimino L, Salvarani C. Visual loss and other cranial ischaemic complications in giant cell arteritis. Nat Rev Rheumatol. 2017; 13:476-84. [2] Ciccia F, Rizzo A, Ferrante A, Guggino G, Croci S, Cavazza A, et al. New insights into the pathogenesis of giant cell arteritis. Autoimmun Rev. 2017; 16:675-83. [3] Calderon-Goercke M. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019Jan5. pii: S0049-0172(18)30571-7. Doi: 10.1016/j.semarthrit.2019.01.003. [Epub ahead of print] Disclosure of Interests Monica Calderon-Goercke: None declared, J. Loricera: None declared, D. Prieto-Pena: None declared, Vicente Aldasoro: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ignacio Villa-Blanco: None declared, Alicia Humbria: None declared, Clara Moriano: None declared, Susana Romero-Yuste: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Catalina Gomez-Arango: None declared, Eva Perez-Pampin: None declared, Rafael Melero: None declared, Elena Becerra-Fernandez: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, Maria Alvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernandez-Lopez: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Eva Galindez: None declared, Beatriz Arca: None declared, Roser Solans-Laque: None declared, Arantxa Conesa: None declared, Cristina Hidalgo: None declared, Carlos Vazquez: None declared, Jose Andres Roman-Ivorra: None declared, Pau Lluch: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., 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, Eugenio de Miguel: None declared, Carmen Torres-Martin: None declared, Juan Carlos Nieto: None declared, Carmen Ordas-Calvo: None declared, Eva Salgado-Perez: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Saenz de Miera: None declared, Nagore Fernandez-Llanio: None declared, Antonio Garcia: None declared, Carmen Larena: None declared, Natalia Palmou-Fontana: None declared, Vanesa Calvo-Rio: None declared, Carmen Gonzalez-Vela: None declared, Alfonso Corrales: None declared, Maria Varela-Garcia: None declared, Elena Aurrecoechea: None declared, Raquel Dos-Santos: None declared, Angel Garcia-Manzanares: None declared, Norberto Ortego: None declared, Sabela Fernandez: None declared, Francisco Ortiz-Sanjuan: None declared, Montserrat Corteguera: None declared, J. Luis Hernandez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background Giant cell arteritis (GCA) can be refractory to corticosteroid therapy. Tocilizumab (TCZ) has been approved in the treatment of GCA. There are no studies comparing the efficacy and safety when using TCZ as monotherapy or in combination with conventional immunosuppressive drugs in GCA. Objectives Our aim was to compare efficacy and safety of TCZ combined or in monotherapy in GCA. Methods Multicenter study on 134 patients with refractory GCA who received TCZ therapy as monotherapy or combined with conventional immunosuppressants. Prolonged remission, absence of clinical symptoms and signs and normalization of the acute phase reactants for at least 6 months. Relapse, recurrence of signs or symptoms of GCA and/or ESR >20 mm/h in men or >25 mm/h in women, and/or serum CRP >0.5 mg/dL related to GCA, both before and after starting TCZ therapy. Results We evaluated 134 patients (101 w/33 m) with a mean age of 73.0±8.8 years. TCZ was prescribed as monotherapy in 82 (62.2%) cases and combined with conventional immunosuppressants in 52 (38.8%) patients: MTX (n=48), AZA (n=3), and LFN (n=1). A comparative study between both groups is summarized in TABLE. Patients who received combined TCZ were younger and had a higher C-reactive protein (CRP) and a higher presence of aortitis in imaging techniques. After TCZ was started, prolonged remission was reached with combined therapy (statistical significance at 12 and 24 months). The corticosteroids sparing effect was similar in both groups. And in terms of side effects no significant difference was seen between TCZ as monotherapy or combined with conventional immunosuppressants. Conclusion Patients receiving combined conventional immunosuppressants with TCZ in the clinical practice study showed a higher prolonged remission. The incidence of serious infections and/or relevant adverse events was not affected according to the treatment. As well as the corticoid-sparing effect was achieved in the same way in both groups. References [1] Goercke .Calderon-M. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Jan 5. pii: S0049-0172(18)30571-7. doi: 10.1016/j.semarthrit.2019.01.003. [Epub ahead of print] [2] Loricera J et al. Semin Arthritis Rheum.2015;44:717-723

Background: Behcet disease (BD) is considered a systemic vasculitis according to the Chapel-Hill classification, which occurs most frequently between latitudes 30 and 45° north and in the area of the Old Silk Route. Turkey has the highest prevalence, followed by Japan. In Spain, a prevalence of 7.5 cases per 100000 persons has been estimated. The epidemiological and clinical characteristics of European patients with BD vary with respect to those of the Turkish and Japanese cohorts. Objectives: Description of clinical features and treatment received in a cohort of patients diagnosed with BD in an internal Medicine Unit of a tertiary centre from Barcelona. Methods: Retrospective, observational study. Epidemiological, clinical and laboratory data were obtained from clinical charts. SSPS package was used to perform statistical analysis. Results: 132 patients (56.6% men) diagnosed over the last 30 years and followed-up until the censoring data were included. 112 (84.8%) were Caucasians, 15 (11.4%) from North africa, 4 (3%) asiatic and 1 (0.8%) from South america. 2 (1.5%) patients had a family history of BD and 9 patients (6.8%) a family history of other rheumatic diseases. 43.9% (58 patients) were HLA-B51. Oral or genital ulcers were present in 131 (99.2%) patients and skin involvement in 106 (80%) cases, 44.6% had erythema nodosum, 59% had acne-like lesions and 9% had cutaneous vasculitis. Ocular involvement was observed in 69 cases (52.3%): 27 patients unilateral and 8 bilateral anterior uveitis; 14 unilateral and 3 bilateral posterior uveitis; 10 patients unilateral and 14 bilateral panuveitis; 19 unilateral retinal vasculitis and 12 bilateral. Neurological involvement was present in 37 (28%) patients: 10 parenchimal disease and 17 cases non-parenchymal disease (aseptic meningitis or vasculitis); 8 patients benign intracranial hypertension, and 3 had dural sinus thrombosis. Articular involvement was recorded in 79 (59.8%) patients (it was observed 25 monoarthritis, 24 oligoarthritis, 6 poliarthritis and 58 patients had arthralgia). Vascular involvement was present in 43 (32.6%) cases: deep venous thrombosis in 38 patients (11 cases in locations other than the extremities); pulmonary embolism in 7; 21 thrombophlebitis; and 6 patients aneurysms (only 2 pulmonary arterial aneurysms). Digestive involvement was present in 12 (9,1%) patients, with predominant colon involvement (8 cases). The most prescribed drugs were corticosteroids (85.6%) and colchicine (77.3%), followed by azathioprine (36.4%) and cyclosporine a (33.3%). Other prescribed drugs were thalidomide (6.1%), chlorambucil (6.9%), methotrexate (4.5%), anti-TNF-alpha therapies (infliximab 6.8% and adalimumab 2.3%), cyclophosphamide (3%), mycophenolate (3.8%), leflunomide (1.5%) and 22% received anticoagulation. Conclusion: Clinical features of our patients are similar to those of other European cohorts, although a high prevalence of organic involvement (ocular, neurological, vascular and joint) should be highlighted. References [1] Saadoun D, Wechsler B. Behcet’s disease. Orphanet J Rare Dis. 2012Apr12;7;20. doi: 10.1186/1750-1172-7-20. [2] Mendes D, et al. Behcet’s disease – a contemporary rewiew. J autoimmun. 2009May-Jun;32 (3-4): 178-88. doi: 10.1016/j.jaut.2009.02.011. [3] Leccese P, et al. Behcet’s sindrome in nonendemic regions. Curr Opin Rheumatol. 2017. doi: 10.1097/BOR.0000000000000349 Disclosure of interests: None declared

Background Recently, based on the GiACTA trial results, weekly subcutaneous Tocilizumab (TCZ) has been approved for the treatment of Giant Cell Arteritis (GCA). It has showed to be effective and safety. Objectives Our aim was to compare the efficacy of TCZ according the route of administration. Methods Multicenter study of 134 GCA patients in treatment with TCZ. It was performed a comparative study between 2 groups according the route of administration of TCZ, intravenous (IV) or subcutaneous (SC). Results We study 134 patients divided in 2 groups: a) IV TCZ, 104 cases and, b) SC TCZ, 30 cases, with a mean age 73.4±8.2 years vs 71.9±10.6 years, respectively (p=0.501). Disease duration, clinical manifestations and acute phase reactants at TCZ onset were similar in both groups with non-statistical difference. 91.7% patients who received SC TCZ achieved prolonged remission after 12 months of treatment (p=0.043). And the glucocorticoid sparing effect of TCZ was greater in the same group, reaching a statistical difference at 3 and 24 months (p=0.017 and p=0.021). Patients under IV TCZ treatment suffered more adverse event during follow up (p=0.043). TABLE 1 and 2 summarizes the comparative study. Conclusion Patients in treatment with SC TCZ, reached prolonged remission after 12 months of treatment and were able to discontinue prednisone dose after 24 months of follow up. The incidence of adverse events was more frequent in the IV TCZ group, without difference in relation to infections. References [1] Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017; 377:317-28. [2] Calderon-Goercke M. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin Arthritis Rheum. 2019 Jan 5. pii: S0049-0172(18)30571-7. doi: 10.1016/j.semarthrit.2019.01.003. [Epub ahead of print] Disclosure of Interests Monica Calderon-Goercke: None declared, J. Loricera: None declared, D. Prieto-Pena: None declared, Vicente Aldasoro: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ignacio Villa-Blanco: None declared, Alicia Humbria: None declared, Clara Moriano: None declared, Susana Romero-Yuste: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Catalina Gomez-Arango: None declared, Eva Perez-Pampin: None declared, Rafael Melero: None declared, Elena Becerra-Fernandez: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, Maria Alvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernandez-Lopez: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Eva Galindez: None declared, Beatriz Arca: None declared, Roser Solans-Laque: None declared, Arantxa Conesa: None declared, Cristina Hidalgo: None declared, Carlos Vazquez: None declared, Jose Andres Roman-Ivorra: None declared, Pau Lluch: None declared, Sara Manrique Arija Speakers bureau: ABBvie, MSD, Janssen, Lillly, Roche, Pfyzer, Novartis., 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, Eugenio de Miguel: None declared, Carmen Torres-Martin: None declared, Juan Carlos Nieto: None declared, Carmen Ordas-Calvo: None declared, Eva Salgado-Perez: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Saenz de Miera: None declared, Nagore Fernandez-Llanio: None declared, Antonio Garcia: None declared, Carmen Larena: None declared, Natalia Palmou-Fontana: None declared, Vanesa Calvo-Rio: None declared, Carmen Gonzalez-Vela: None declared, Alfonso Corrales: None declared, Maria Varela-Garcia: None declared, Elena Aurrecoechea: None declared, Raquel Dos-Santos: None declared, Angel Garcia-Manzanares: None declared, Norberto Ortego: None declared, Sabela Fernandez: None declared, Francisco Ortiz-Sanjuan: None declared, Montserrat Corteguera: None declared, J. Luis Hernandez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background Aortitis can be idiopathic or associated with other conditions. It is frequently refractory to conventional immunosuppressive therapy. Tocilizumab (TCZ), an anti-IL-6 receptor antibody seems to be effective and safe. Objectives Our aim was to assess the efficacy and safety of TCZ at short and long follow-up in a series of patients with Aortitis. Methods Retrospective, multicenter study of 79 patients diagnosed of inflammatory aortitis based on imaging techniques (PET/CT, CT angiography and/or MR angiography). Results We study 79 patients (61 w/ 18 m). 59 (74.7%) cases were Aortitis secondary to Giant Cell Arteritis (GCA), while 20 (25.3%) were idiopathic. The mean age was 71±8.5 years vs 64.2±7.1 years, respectively (p=0.001). At time of disease diagnosis more than a half of patients (59.5%) presented as main symptom polymyalgia rheumatica (PMR). Aortitis was diagnosed with PET/CT (71 patients), angioRMN (12 patients) and angioCT (8 patients). Prior to TCZ treatment, 61 (77.2%) patients had received conventional immunosuppressive drugs, 59 (74.7%) of them received MTX. After 24 months of treatment with TCZ, more than 75% of patients reached a prolonged remission in both groups (p=0.527), with only 4% of relapses after the same follow-up period (p=1.000). 40 (50.6%) patients had a control image technique (PET/CT) throughout follow up. 4 (3 secondary to GCA and 1 idiopathic) patients reached a complete improvement in uptake after one year of treatment. Conclusion Our results show that idiopathic aortitis occurs in younger patients compared with aortitis secondary to GCA. TCZ proved to be effective in both pathologies, allowing clinical and analytical improvement, as well as a reduction of corticoid dose, without increasing the risk of relapse. However, the improvement in imaging techniques seems to be slower. Reference [1] Loricera J, Blanco R, Castaneda S, Humbria A, Ortego-Centeno N, Narvaez J, et al. Tocilizumab in refractory aortitis: study on 16 patients and literature review. Clin Exp Rheumatol. 2014; 32:79-89. Disclosure of Interests Monica Calderon-Goercke: None declared, J. Loricera: None declared, D. Prieto-Pena: None declared, Vicente Aldasoro: None declared, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Ignacio Villa-Blanco: None declared, Alicia Humbria: None declared, Clara Moriano: None declared, Susana Romero-Yuste: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Catalina Gomez-Arango: None declared, Eva Perez-Pampin: None declared, Rafael Melero: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Francisca Sivera: None declared, Maria Alvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Eva Galindez: None declared, Beatriz Arca: None declared, Roser Solans-Laque: None declared, Carlos Vazquez: None declared, Pau Lluch: None declared, Eva Salgado-Perez: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Saenz de Miera: None declared, Nagore Fernandez-Llanio: None declared, Antonio Garcia: None declared, Carmen Larena: None declared, Natalia Palmou-Fontana: None declared, Vanesa Calvo-Rio: None declared, Carmen Gonzalez-Vela: None declared, Alfonso Corrales: None declared, Maria Varela-Garcia: None declared, Elena Aurrecoechea: None declared, Raquel Dos-Santos: None declared, Jose Luis Martin-Varillas: None declared, Sabela Fernandez: None declared, J. Luis Hernandez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Objectives To analyse how the age at diagnosis modifies the phenotype of primary Sjogren syndrome (SS) Methods The Big Data Sjogren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS at diagnosis by merging international SS databases. By January 2019, the database included 11,420 patients from 24 countries of the 5 continents. Results Women (52.7 vs 54.6 yrs in men, p Patients with positive immunological markers had a younger diagnostic age, except for cryoglobulins (p Patients without systemic activity (ESSDAI score = 0) were diagnosed at an older age (55.5 vs 52.1 yrs in those with systemic activity, p Conclusion Age at diagnosis plays a key role in the glandular and systemic phenotype expressed by primary SjS patients at the time of diagnosis. Disclosure of Interests: Soledad Retamozo: None declared, Nihan Acar-Denizli: None declared, Wan Fai Ng: None declared, Ildiko Fanny Horvath: None declared, Astrid Rasmussen: None declared, Raphaele Seror Grant/research support from: Pfizer, Consultant for: Bristol-Myers Squibb, Pfizer, Amgen, Eli Lilly, Roche, Celgene, GlaxoSmithKline, MedImmune, Xiaomei Li: None declared, Chiara Baldini: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Pulukool Sandhya: None declared, Luca Quartuccio: None declared, Roberta Priori: None declared, Gabriela Hernandez-Molina: None declared, Berkan Armagan: None declared, Aike A. Kruize: None declared, Seung-Ki Kwok: None declared, Marika Kvarnstrom: None declared, Sonja Praprotnik: None declared, Damien Sene: None declared, Elena Bartoloni Bocci: None declared, Roser Solans-Laque: None declared, Maureen Rischmueller Consultant for: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Thomas Mandl: None declared, Yasunori Suzuki: None declared, David Isenberg: None declared, Valeria Valim: None declared, Agata Sebastian: None declared, Gunnel Nordmark: None declared, Hendrika Bootsma: None declared, Hideki Nakamura: None declared, Roberto Giacomelli Grant/research support from: Pfizer, Actelion, Speakers bureau: Actelion, Bristol-Myers Squibb, Merck Sharp & Dohme, Abbvie, Pfizer, Sobi, Roche, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Benedikt Hofauer Consultant for: Consultant for Galvani Bioelectronics for the area of sleep disorders., Michele Bombardieri Grant/research support from: Celgene, Consultant for: Medimmune, Virginia Fernandes Moca Trevisani: None declared, Daniel Hammenfors: None declared, Sandra Pasoto: None declared, Tamer A Gheita: None declared, Fabiola Atzeni: None declared, Jacques Morel: None declared, Cristina Vollenveider: None declared, Sandra Consani-Fernandez: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Manuel Ramos-Casals: None declared, Pilar Brito-Zeron: None declared

Background Giant cell arteritis (GCA) is a large vessel vasculitis with a predisposition for the cranial branches of the external carotid artery. However, aorta and/or its main branches may also be involved. Objectives In a series of patients with GCA who presented extracranial vessel involvement, our aim was to assess a) the vascular territories most frequently affected and b) correlation of a major extension of extracranial vascular involvement with a more severe clinical and analytical features. Methods Multicenter study of 68 patients with GCA who presented a compromise of extracranial vessels confirmed by PET/CT. Visual analysis of vascular uptake was performed on supra-aortic trunks (SAT), aortic arch (AA), thoracic aorta (TA), abdominal aorta (AbA), iliac arteries (IA), lower limb arteries (LLA), and upper limb arteries (ULA). Results We evaluated 68 patients with GCA (51w/17m) with a mean age of 68.0±8.3 years. The vascular territories affected were: TA (n=58, 85.29%), SAT (n=38, 55.88%), AbA (n=28, 41.18%), AA (n=18, 26.47%), LLA (n=17, 25%), IA (n=13, 19.12%) and ULA (n=6, 8.82%). We considered 3 groups according to the number of vascular territories affected: a) 1 or 2 territories, b) 3 or 4 territories and c) 5 or more territories and made a comparative study between this groups. In patients with ≥5 vascular territories affected, we observed a higher baseline ESR, and the most frequent systemic manifestations were polymyalgia rheumatica and constitutional symptoms with statistical significance (TABLE). Distribution of categorical variables was compared by the Pearson Chi-squared test. Quantitative variables were analyzed using the ANOVA test. Conclusion In patients with GCA the involvement of TA is very frequent, followed by the SAT and the AbA. Regarding the laboratory findings, patients with higher levels of ESR presented a major extension of extracranial vascular involvement, as well as presenting PMR and/or constitutional symptoms was also related to more affection of extracranial territories. References [1] Loricera J, Blanco R, Hernaandez JL, et al. Use of positron emission tomography (PET) for the diagnosis of large-vessel vasculitis. Rev Esp Med Nucl Imagen Mol. 2015; 34: 372-377. [2] Loricera J, Blanco R, Hernaandez JL, et al. Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review. Clin Exp Rheumatol. 2015; 33: S19-31. Disclosure of Interests Monica Calderon-Goercke: None declared, J. Loricera: None declared, D. Prieto-Pena: None declared, J. Narvaez Consultant for: Bristol-Myers Squibb, Santos Castaneda Consultant for: Amgen, BMS, Pfizer, Lilly, MSD, Roche, Sanofi, UCB, Elena Aurrecoechea: None declared, Ignacio Villa-Blanco: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampin: None declared, Vicente Aldasoro: None declared, Noelia Alvarez-Rivas: None declared, Nagore Fernandez-Llanio: None declared, Maria Alvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Francisca Sivera: None declared, Eva Galindez: None declared, Roser Solans-Laque: None declared, Susana Romero-Yuste: None declared, Norberto Ortego: None declared, Marcelino Revenga: None declared, Rafael Melero: None declared, Eva Salgado-Perez: None declared, Sabela Fernandez: None declared, Vanesa Calvo-Rio: None declared, Natalia Palmou-Fontana: None declared, Jose Ignacio Banzo: None declared, Isabel Martinez-Rodriguez: None declared, Carmen Gonzalez-Vela: None declared, Raquel Dos-Santos: None declared, J. Luis Hernandez: None declared, Miguel A Gonzalez-Gay Grant/research support from: Prof. MA Gonzalez-Gay received grants/research supports from Abbvie, MSD, Jansen and Roche., Speakers bureau: Consultation fees/participation in company sponsored speaker’s bureau from Pfizer, Lilly, Sobi, Celgene, Novartis, Roche and Sanofi., Ricardo Blanco Grant/research support from: Abbvie, MSD, and Roche, Consultant for: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen

Background: Eosinophilic granulomatosis with polyangiitis (EGPA), formerly Churg-Strauss syndrome, is a rare type of anti-neutrophil cytoplasm antibody-associated vasculitis, associated with asthma, nasal poliposis and rinosinusitis, in which eosinophils paly a key role. Eosinophil targeted therapies alone or associated to conventional treatment with corticosteroids and immunosuppressant drugs may be useful in patients with refractory disease or asthma difficult to treat. Objectives: To describe the efficacy and safety of eosinophil targeted therapies in patients with relapsing or refractory EGPA Methods: Retrospective study including all patients with EGPA included at the REVAS Registry, who were treated with omalizumab, mepolizumab or resilizumab. Complete response (CR) was defined as the absence of asthma and/or sinonasal exacerbations with a prednisone dosage of ≤ 7.5 mg/day, and partial response (PR) when the prednisone dosage was ≥ 7.5 mg/day. Statistical analysis was performed using SSPS 20 package. Results: Seventeen patients (median age 49 years) received omalizumab (n=9) for a mean period of 53.4 (5-91) months, mepolizumab (n=7) for a mean period of 13.6 (5-16) months, or resilizumab (n=1) for a mean period of 7 months, for severe steroid-dependent asthma (94.1%) and/or sinonasal involvement (82.4%). ANCA were positive in 8 (47.1%) cases with MPO specificity in 7 cases. All patients were receiving corticosteroids with a mean dosage of 15 mg/day prior to eosinophil targeted therapies institution. Four (57.1%) patients treated with omalizumab achieved a CR, 1 a PR, and 2 had no improvement. The median dosage of prednisone 6 months after omalizumab initiation was 10 (2.5-10) mg/day and the median dosage after 12 months 5 (0-10) mg/day. The median number of exacerbations decreased from 4 over the 6 months previous to therapy startment to 2 in the following 12 months. Both patients refractory to omalizumab were treated with mepolizumab with CR at 6 months in 1 case. Treatment with mepolizumab was also started in 4 patients treated with omalizumab after a prolonged period of treatment (72.4 months), due to recurrence of asthma and/or sinusitis, and peripheral blood eosinophilia >10%. Three (75%) patients achieved a CR, and 1 patient experienced a major vasculitis relapse needing immunosuppressant drugs. Six (85.7%) patients initially treated with mepolizumab achieved a complete remission after 6-12 months of treatment. One patient achieved a PR. The median dosage of prednisone 6 months after mepolizumab initiation was 5 (3.1-6.8) mg/day and the median dosage after 12 months 3.5 (0-5) mg/day. The median number of exacerbations decreased from 2.5 over the 6 months previous to therapy startment to 1 in the following 12 months. The patient treated with resilizumab achieved a CR at 6 months of therapy. All 3 drugs were safe and well tolerated. Conclusion: The results of the present study suggest that eosinophil targeted therapies have a corticosteroid-sparing effect in EGPA patients with asthmatic and/or sinonasal manifestations, and that may be used sequentially in refractory cases. However, reducing the corticosteroid dosage may also increase the risk of severe EGPA flares. More data are needed to widely recommend this therapy in EGPA patients. References: [1] AntiIgE monoclonal antibody (omalizumab) in refractory and relapsing Eosinohilic granulomatosis with polyangiitis (Churg-Struss). Arthritis Rheum 2016; 68: 2274-82 Disclosure of Interests: None declared

Objectives To analyse the phenotype of patients with primary Sjogren syndrome (SjS) in whom a lymphoproliferative disease is diagnosed concomitantly. Methods By January 2019, The Big Data Sjogren Project included 11,420 consecutive patients with primary SjS recruited from 24 countries of the five continents. Results 117 (1%) patients were diagnosed with lymphoma and primary SjS synchronously. Age-gender adjusted multivariate analysis identified the following features associated with lymphoma (OR; CI95%): male gender (4.61; 2.88-7.18), White ethnicity (3.51; 1.78-7.91), abnormal oral tests (3.4; 1.38-10.88), positive biopsy (3.2; 1.3-10.17), positive RF (2.27; 1.48-3.53), hypocomplementemia (3.39; 2.06-5.54), and cryoglobulins (4.74; 2.57-8.38). Activity (score > 1) in the constitutional (2.97; 1.86-4.62), glandular (3.11; 2.1-4.57), cutaneous (2.17; 1.28-3.52), peripheral nerve (2.56; 1.4-4.41) and hematological (2.49; 1.64-3.75) ESSDAI domains was associated with lymphoma (frequencies summarized in the Figure). Conclusion Patients diagnosed concomitantly with primary SjS and lymphoma have a very specific, highly-active phenotype (men, White, severe oral involvement, cryoglobulinemic-related immunological markers, and high systemic activity). Disclosure of Interests: Soledad Retamozo: None declared, Nihan Acar-Denizli: None declared, Wan Fai Ng: None declared, Antonia Szanto: None declared, Astrid Rasmussen: None declared, Raphaele Seror Grant/research support from: Pfizer, Consultant for: Bristol-Myers Squibb, Pfizer, Amgen, Eli Lilly, Roche, Celgene, GlaxoSmithKline, MedImmune, Xiaomei Li: None declared, Chiara Baldini: None declared, Jacques-Eric Gottenberg Grant/research support from: Bristol-Myers Squibb, Grant/research support from: Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Lilly, Pfizer, Sanofi-Genzyme, UCB Pharma, Consultant for: Bristol-Myers Squibb, Eli Lilly, UCB, Sanofi-Genzyme, Pfizer, Pulukool Sandhya: None declared, Luca Quartuccio: None declared, Roberta Priori: None declared, Gabriela Hernandez-Molina: None declared, Berkan Armagan: None declared, Aike A. Kruize: None declared, Seung-Ki Kwok: None declared, Marika Kvarnstrom: None declared, Sonja Praprotnik: None declared, Damien Sene: None declared, Roser Solans-Laque: None declared, Maureen Rischmueller Consultant for: Abbvie, Bristol-Meyer-Squibb, Celgene, Glaxo Smith Kline, Hospira, Janssen Cilag, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, Thomas Mandl: None declared, Yasunori Suzuki: None declared, David Isenberg: None declared, Valeria Valim: None declared, Agata Sebastian: None declared, Gunnel Nordmark: None declared, Hendrika Bootsma: None declared, Hideki Nakamura: None declared, Roberto Giacomelli Grant/research support from: Pfizer, Actelion, Speakers bureau: Actelion, Bristol-Myers Squibb, Merck Sharp & Dohme, Abbvie, Pfizer, Sobi, Roche, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Benedikt Hofauer Consultant for: Consultant for Galvani Bioelectronics for the area of sleep disorders., Michele Bombardieri Grant/research support from: Celgene, Consultant for: Medimmune, Virginia Fernandes Moca Trevisani: None declared, Daniel Hammenfors: None declared, Sandra Pasoto: None declared, Tamer A Gheita: None declared, Fabiola Atzeni: None declared, Jacques Morel: None declared, Cristina Vollenveider: None declared, Sandra Consani-Fernandez: None declared, Xavier Mariette Grant/research support from: Servier, Consultant for: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, UCB Pharma, Manuel Ramos-Casals: None declared, Pilar Brito-Zeron: None declared, Elena Bartoloni Bocci: None declared

Objective.To analyze the role that infections play on the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) outcome.Methods.A retrospective study of adult patients with AAV diagnosed in a tertiary center. Clinical features, laboratory findings, treatment, relapses, major infections, and outcome were evaluated.Results.Included were 132 patients [51 microscopic polyangiitis (MPA), 52 granulomatosis with polyangiitis (GPA), 29 eosinophilic GPA (EGPA)] with a mean followup of 140 (96–228) months. ANCA were positive in 85% of cases. A total of 300 major infections, mainly bacterial (85%), occurred in 60% patients during the followup. Lower respiratory tract (64%) and urinary tract infections (11%) were the most frequent, followed by bacteremia (10%). A total of 7.3% opportunistic infections were observed, most due to systemic mycosis. Up to 46% of all opportunistic infections took place in the first year of diagnosis, and 55% of them under cyclophosphamide (CYC) treatment. Bacterial infections were associated with Birmingham Vasculitis Activity Score (version 3) > 15 at the disease onset, a total cumulative CYC dose > 8.65 g, dialysis, and development of leukopenia during the followup. Leukopenia was the only factor independently related to opportunistic infections. Forty-four patients died, half from infection. Patients who had major infections had an increased mortality from any cause.Conclusion.Our results confirm that major infections are the main cause of death in patients with AAV.

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.

Background:Tocilizumab (TCZ) has shown to be effective for large vessel vasculitis including Takayasu arteritis (TAK) (1-3). Most evidence in TAK comes from Asian patients. However, white patients seem to have different clinical and prognostic features.Objectives:Our aims were to: a) assess the efficacy and safety of TCZ in white patients with refractory TAK, b) determine if clinical improvement correlates with imaging outcomes, c) compare TCZ in monotherapy (TCZMONO) vs combined with conventional immunosuppressive drugs (TCZCOMBO)Methods:Multicenter study of white patients with refractory TAK who received TCZ.Outcomes variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZMONO and TCZCOMBO was performed.Results:54 patients (46 women/8 men; median age 42.0 [32.5-50.5] years). TCZ was started after 12.0 [3.0-31.5] months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%) and 27/36 (75%) at 1, 3, 6 and 12 months, respectively. Prednisone dose was reduced from 30.0 [12.5-50.0] to 5.0 [0.0-5.6] mg/day at 12 months (Table 1). 10 (26.3%) of the 38 patients in whom an imaging follow-up test was performed showed no radiographic improvement after a median of 9.0 [6.0-14.0] months. 4 of them were in clinical remission.23 (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n=28), cyclosporine A (n=2), azathioprine (n=1). Patients on TCZCOMBO were younger (38.0 [27.0-46.0] vs 45 [38.0-57.0] years; p= 0.048), with a trend to longer TAK duration (21.0 [6.0-38.0] vs 6.0 [1.0-23.0] months; p= 0.08) and higher C-reactive protein (2.4 [0.7-5.6] vs 1.3 [0.3-3.3] mg/dL; p=0.16). Despite these differences, similar outcomes were observed in both groups (log rank p=0.862) (Figure 1). Relevant adverse events were reported in 6 (11.1%) patients, but only 3 developed severe events that required TCZ withdrawal.Table 1.Baselinen=54Month 1N=54Month 3N=49Month 6N=44Month 12N=36Clinical remission, n (%)12 (22.2)19 (38.8)23 (52.3)27 (75.0)Laboratory improvementCRP (mg/dL), median [IQR]1.5 [0.5-3.5]0.2 [0.1-0.7]*0.2 [0.5-0.5]*0.2 [0.1-0.5]*0.1 [0.0-0.4]*ESR (mm/1sthour), median [IQR]30.5 [8.7-52.7]7.0 [3.0-14.0]*4.5 [2.0-8.0]*5.0[2.0-6.0]*4.0 [2.0-9.5]*Hemoglobin (g/dL), mean ± SD12.4 ±1.513.0 ±1.2*13.0 ±1.4*13.2 ±1.5*12.9 ±1.6*Prednisone dose, median [IQR]30.0 [12.5-50.0]20.0 [10.0-30.0]*10.0 [5.0-20.0]*5.0 [5.0-10.5]*5.0 [0.0-5.6]*CRP: C-Reactive Protein; ESR: Erythrocyte Sedimentation Rate; IQR: interquartile range; n: number. *pConclusion:TCZ is effective and safe in white patients with refractory TAK. A discordance between clinical and imaging activity assessment may exist.References:[1]Prieto Peña D et al. Clin Exp Rheumatol 2020 Nov 27. PMID: 33253103.[2]Loricera J, et al. Clin Exp Rheumatol 2016; 34:S44-53. PMID: 27050507.[3]Calderón-Goercke M, et al. Semin Arthritis Rheum 2019; 49:126-35. PMID: 30655091Disclosure of Interests:Diana Prieto-Peña Grant/research support from: DP-P has received research support from UCB Pharma, Roche, Sanofi, Pfizer, AbbVie and Lilly., Pilar Bernabéu: None declared, Paloma Vela-Casasempere: None declared, J. Narváez: None declared, Carlos Fernández-López: None declared, Mercedes Freire González: None declared, Beatriz González-Alvarez: None declared, Roser Solans-Laqué: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Carlos Fernández-Díaz: None declared, Esteban Rubio Romero: None declared, SALVADOR GARCÍA MORILLO: None declared, Mauricio Minguez: None declared, Cristina Fernández-Carballido: None declared, Eugenio de Miguel: None declared, Sheila Melchor: None declared, Eva Salgado-Pérez: None declared, Beatriz Bravo: None declared, Susana Romero-Yuste: None declared, Juan Salvatierra: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, C. Romero-Gómez: None declared, Patricia Moya: None declared, Noelia Alvarez-Rivas: None declared, Javier Mendizabal: None declared, Francisco Miguel Ortiz Sanjuan: None declared, I. Pérez de Pedro: None declared, JOSE LUIS ALONSO VALDIVIESO: None declared, Pérez Sánchez Laura: None declared, Roldán Molina Rosa: None declared, Nagore Fernández-Llanio: None declared, Ricardo Gómez de la Torre: None declared, Silvia Suarez: None declared, María Jesús Montesa: None declared, Monica Delgado Sanchez: None declared, J. Loricera: None declared, Belén Atienza-Mateo: None declared, Santos Castañeda: None declared, Miguel A González-Gay Grant/research support from: MAG-G received grants/research supports from Abbvie, MSD, Jansen and Roche and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene and MSD, Ricardo Blanco Grant/research support from: RB received grants/research supports from Abbvie, MSD and Roche, and had consultation fees/participation in company sponsored speaker´s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD.

Background:Tocilizumab (TCZ) was recently approved for Takayasu Arteritis (TAK) in Japan based on the results of the TAKT trial(1).However, data in clinical practice in Europe and America are scarce(2).Objectives:To assess efficacy and safety of TCZ in TAK of clinical practice in Spain.Methods:Observational, open-label multicentre study of 53 TAK patients treated with TCZ due to refractoriness or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants and glucocorticoid-sparing effect.Results:53 patients (46w/7m); mean age, 40.6±14.6 years at TCZ onset. TCZ was started after a median of 12 [3.0-48.0] months from TAK diagnosis. In addition to systemic corticosteroids and before TCZ they received conventional immunosuppressant drugs (n=42) and biologic therapy (n=14). TCZ was prescribed as standard I.V. (n=42; 79.2%) or subcutaneous (n=11; 20.8%). The initial dose was 8 mg/kg/IV/4 weeks or 162 mg/SC/week, respectively. TCZ was used in monotherapy or combined with immunosuppressants (n=32; 60.4%): methotrexate (n=27), azathioprine (n=2), cyclosporine (n=3). Main clinical features at TCZ onset were: malaise (n=30),limb claudication (n=22), headache (n=18), fever (n=14), abdominal pain (n=10), and chest pain (n=9). Most of the patients experienced a rapid and maintained clinical, analytical improvement(TABLE).After a median follow-up of 18.0 [7.0-45.0] months, TCZ was discontinued in 20 patients due to: sustained remission (n=6), relapse (n=6), adverse event (n=5), gestation (n=3). Most relevant adverse side effects were serious infections: pneumonia (n=2), herpes zoster (n=1), abdominal sepsis (n=1).Table.Basal(N=53)Month 1(N=53)Month 3(N=46)Month 6(N=44)Month 12(N=34)Clinical improvement, n/N(%)Complete17/53 (32.1)19/46 (41.3)23/44 (52.3)26/34 (76.5)Partial30/53 (54.6)26/46 (56.5)18/44 (40.9)8/34 (23.5)No improvement6/53 (11.3)1/46 (2.2)3/44 (6.8)0/34 (0.0)Analytical markers,ESR (mm/1sth),median [IQR]35.0 [16.0-52.0]7.5 [3.0-14.0] *3.5 [2.0-8.0]*5.0[2.0-6.0]*5.0 [2.0-8.5]*CRP (mg/dL),median [IQR]1.7 [0.6 -3.5]0.21 [0.05-0.6]*0.14 [0.05-0.5]*0.14 [0.04-0.4]*0.10 [0.03-0.30]*Hb (g/dL),mean±SD12.3±1.512.8±1.2*12.9±1.3*12.9±1.4*12.9±1.4*Prednisone dose (mg/day),median [IQR]30.0 [15.0-50.0]20.0 [10.0-37.5]*10.0 [5.0-20.0]*5.0 [5.0-12.5]*5.0 [0.0-7.5]**Wilcoxon test p < 0.001.Conclusion:TCZ appears to be effective and safe in patients with refractory TAK in clinical practice.References:[1]Nakaoka Y et al. Ann Rheum Dis. 2018;77:348-354[2]Loricera J et al. Clin Exp Rheumatol. 2016; 34: S44-53.Disclosure of Interests:D. Prieto-Peña: None declared, Monica Calderón-Goercke: None declared, Pilar Bernabéu: None declared, Paloma Vela-Casasempere: None declared, J. Narváez: None declared, Carlos Fernández-López: None declared, Mercedes Freire González: None declared, Beatriz González-Alvarez: None declared, Roser Solans-Laqué: None declared, Jose Luis Callejas-Rubio: None declared, Norberto Ortego: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Esteban Rubio Romero: None declared, SALVADOR GARCÍA MORILLO: None declared, Mauricio Minguez: None declared, Cristina Fernández-Carballido Consultant of: Yes, I have received fees for scientific advice (Abbvie, Celgene, Janssen, Lilly and Novartis), Speakers bureau: Yes, I have received fees as a speaker (Abbvie, Celgene, Janssen, Lilly, MSD, Novartis), Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Sheila Melchor: None declared, Eva Salgado-Pérez: None declared, Beatriz Bravo: None declared, Susana Romero-Yuste: None declared, J Salvatierra: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, C. Romero-Gómez: None declared, Patricia Moya: None declared, Noelia Alvarez-Rivas: None declared, Javier Mendizabal: None declared, Francisco Miguel Ortiz Sanjuan: None declared, I. Pérez de Pedro: None declared, Javier Loricera: None declared, Santos Castañeda: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, Roche, Consultant of: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma and MSD, Speakers bureau: Abbvie, Eli Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma. MSD

Background:Infections are the most common adverse event of Tocilizumab (TCZ) in Giant Cell Arteritis (GCA). In GiACTA study(1),serious infections were observed in 7% (9.6/100 patient-years) of patients who received TCZ weekly. Randomized clinical trials (RCTs) are conducted under highly standardized design excluding some real-world patients. Therefore, adverse events may be underestimated in RCTs. In our series of real-life, serious infections occurred in 11.9% (10.6/100 patient-years)(2).Objectives:In a wide series of GCA of clinical practice treated with TCZ, we assess the frequency, type and predisposing factors of serious infections.Methods:Multicenter study of 134 patients diagnosed with GCA, all of them refractory to conventional therapy, treated with TCZ. Serious infection was considered when a life-threatening infection, fatal, or requiring hospitalization occurred, intravenous antibiotics were required, or the infectious process led to persistent or significant disability.Results:16 of 134 (11.9%, 10.6/100 patient-years) patients developed serious infections during follow-up. The most frequent infections were pneumonia (n=4), urinary tract infection (n=4), and facial herpes zoster (n=2). At TCZ onset, serious infections were more frequent in older patients (74.3±9.6 vs 72.9±8.7 years), with a longer GCA evolution (20 [4.3-45.6] vs 13 [5-29.3] months), with visual manifestations (43.75% vs 17.8%) and a higher dose of prednisone at TCZ onset (30.4±15.5 vs 21.1±16.1 mg/day) (TABLE). Presence of comorbidities were similar in both groups. 13 of the 16 patients who had infections received a dose of prednisone greater than 15 mg/day (16.3/100 patient-years) compared to 3 patients under treatment with less than 15 mg/day of prednisone (4.2/100 patient-years).Conclusion:The age, GCA duration, ocular involvement and the dose of glucocorticoids, at TCZ onset, seem to be predisposing factors related to an increased risk of developing serious infections in GCA patients.References:[1]Stone JH, et al. N Engl J Med. 2017; 377:317-28.[2]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLESERIOUS INFECTIONS(n=16)WITHOUT SERIOUS INFECTIONS(n=118)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURES Age, years, mean± SD74.3±9.672.9±8.70.552 Sex, female/male n(%)13/388/300.760 Time from GCA diagnosis to TCZ onset (months), median [IQR]20[4.3-45.6]13[5-29.3]0.604COMORBIDITIES Hypertension, n(%)9(56)86(73)0.551 Diabetes, n(%)3(19)39(33)0.677 Chronic kidney disease, n(%)3(19)27(23)0.512CLINICAL FEATURES OF GCA PMR, n(%)9(56.25)64(54.2)0.879 Aortitis, n(%)5(31.25)53(45)0.301 Visual manifestations, n(%)7(43.75)21(17.8)0.017CORTICOSTEROIDS AT TCZ ONSET Prednisone dose mg/d, mean (SD)30.4±15.521.1±16.10.031Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Carlos Fernández-Díaz Speakers bureau: Brystol Meyers Squibb, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, Carmen González-Vela: None declared, Javier García-Fernández: None declared, Patricia Vicente-Gómez: None declared, Ángel García-Manzanares: None declared, Norberto Ortego: None declared, Francisco Ortiz-Sanjuán: None declared, Montserrat Corteguera: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background:Tocilizumab (TCZ) is the only biological agent approved in Giant Cell Arteritis (GCA). There is general agreement on the initial and the standard maintenance dose of TCZ. However, information on duration and optimization of TCZ in GCA is scarce.Objectives:Our aim was to assess efficacy and safety of TCZ therapy optimization in an unselected wide series of GCA in clinical practice.Methods:Multicenter study, 134 patients with GCA who received TCZ due to inefficacy/adverse events of previous therapy. Once complete remission was reached and based on a shared decision between patient and physician TCZ was optimized in some cases. Optimization was done by decreasing the dose and/or prolonging the TCZ dosing interval progressively.Results:134 GCA patients treated with TCZ (101w/33m); mean age 73.0±8.8 years. TCZ was administered IV to 106 (79.1%) patients and SC to 28 (20.9%). TCZ was optimized in 43 (32.1%) patients. No demographic, clinical manifestations or laboratory data differences had been found at TCZ onset (TABLE). After a follow up of 12 [6-15.5] months, and a complete remission for 6 [3-12] months; the first TCZ optimization was performed. Median prednisone dose at first TCZ optimization was 2.5 [0-5] mg/day. TCZ IV was optimized from 8 to 4 mg/kg/4weeks in 12 of 106 (11.3%) and from 162 mg/SC/week to 162 mg/SC/2weeks in 9 of 28 (32.1%) cases. Five (11.6%) of the 43 optimized cases relapsed. In 4 cases, the relapses were treated increasing TCZ up to the pre-optimization dose, in 1 case the route of administration was change (4 mg/kg/4week to 162 mg/SC/week). In 8 of 43 optimized patients (18.6%), it was possible to withdraw TCZ after complete remission for 30 [16.25-45.75] months. Regarding adverse events and severe infections were similar in both groups. The mean TCZ treatment costs were lower in the optimized group.Conclusion:Once remission is reached in GCA patients under TCZ treatment, optimization of TCZ may be performed. Based on our experience it could be performed by reducing the dose with IV TCZ or by prolonging dosing interval with SC TCZ.References:[1]Calderón-Goercke M et al. Semin Arthritis Rheum 2019 Aug;49(1): 126-135.TABLE.OPTIMIZED-TCZ GROUP (n=43)NON-OPTIMIZED TCZ GROUP (n=91)pBASAL FEATURES AT TCZ ONSETGENERAL FEATURESAge, years, mean± SD68.9±8.771.4±8.50.125Sex, female/male n(%)32/1068/240.779Time from GCA diagnosis to TCZ onset (months), median [IQR]19.5[7.75-45]10.5[4 – 25]0.047SYSTEMIC MANIFESTATIONSFever, n(%)1(2.4)8(8.7)0.176Constitutional syndrome, n(%)11(26.2)19(20.7)0.476PMR, n(%)18(42.9)56(60.9)0.052ISCHEMIC MANIFESTATIONSVisual involvement, n(%)5(11.9)23(25)0.084Headache, n(%)26(61.9)42(45.7)0.081Jaw claudication, n(%)1(2.4)11(12)0.072CORTICOSTEROIDS AT TCZ ONSETPrednisone dose, mg/d mean (SD)15.1±11.125±17.40.001FOLLOW-UP ON TCZ THERAPY (MONTHS), MEDIAN [IQR]24[18-27]6 [3-18]0.000Relapses, n(%)5(11.6)5(5.5)0.207End follow-up remission, n(%)40(93)84(92)0.99Severe side efects, n(%)14(32.6)22(24.2)0.307Seriuos infections, n(%)6(14)10(11)0.878Cost, (mean) euros per yearIVSC7 538.47 329.011 726.411 726.4--Disclosure of Interests:Monica Calderón-Goercke: None declared, D. Prieto-Peña: None declared, Santos Castañeda: None declared, Clara Moriano: None declared, Elena Becerra-Fernández: None declared, Marcelino Revenga: None declared, Noelia Alvarez-Rivas: None declared, Carles Galisteo: None declared, Águeda Prior-Español: None declared, E. Galindez: None declared, Cristina Hidalgo: None declared, Sara Manrique Arija: None declared, Eugenio de Miguel Grant/research support from: Yes (Abbvie, Novartis, Pfizer), Consultant of: Yes (Abbvie, Novartis, Pfizer), Paid instructor for: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Speakers bureau: yes (AbbVie, Novartis, Pfizer, MSD, BMS, UCB, Roche, Grunental, Janssen, Sanofi), Eva Salgado-Pérez: None declared, Vicente Aldasoro Speakers bureau: Roche, Abbvie, MSD, UCB, Pfizer, Menarini, Grunenthal, Gebro, Novartis, Janssen, Ignacio Villa-Blanco Consultant of: UCB, Speakers bureau: Novartis, MSD, Lilly, Susana Romero-Yuste: None declared, J. Narváez: None declared, Catalina Gomez-Arango: None declared, Eva Perez-Pampín: None declared, Rafael Melero: None declared, Francisca Sivera: None declared, Alejandro Olive: None declared, María Álvarez del Buergo: None declared, Luisa Marena Rojas: None declared, Carlos Fernández-López: None declared, Francisco Navarro: None declared, Enrique Raya: None declared, Beatriz Arca: None declared, Roser Solans-Laqué: None declared, Arantxa Conesa: None declared, Carlos Vázquez: None declared, Jose Andrés Román-Ivorra: None declared, Pau Lluch: None declared, Paloma Vela-Casasempere: None declared, Carmen Torres-Martín: None declared, Juan Carlos Nieto Speakers bureau: Pfizer, Abbvie, MSD, Novartis, Janssen, Lilly, Nordic Pharma, BMS, Gebro, FAES Farma, Roche, Sanofi, Carmen Ordas-Calvo: None declared, Cristina Luna-Gomez: None declared, Francisco J. Toyos Sáenz de Miera: None declared, Nagore Fernández-Llanio: None declared, Antonio García: None declared, J. Luis Hernández: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

Background Anti-Ro52 antibodies have been described in patients with Sjogren syndrome (SS) but there are limited data on their significance, and they are not included in the diagnostic criteria of SS. Objectives To analyse the clinical and immunological characteristics of patients with suspected SS and positive anti-Ro52 antibodies, and to assess the diagnostic value of this antibodies. Methods retrospective study of all patients evaluated at our Department between January 2000 and January 2016 for possible SS in which anti-Ro52 abs. were determined. Patients were classified as having SS, according to the 2002 European-American Consensus Group (EACG) criteria. Statistical analysis was performed using the SPSS vs.20 package Results 348 patients (331 women), mean age at diagnosis 56.12±14.19 years (range 22–92), with possible SS were analysed. All patients met the European criteria for SS diagnosis, and 242 the EACG criteria. AAN were positive in 345 (99.4%) patients, RF in 169 (48.4%), anti-Ro60/SSA in188 (54%), and anti-La/SSB in 11 (32%). Anti-Ro52 abs. were positive in 173 (49.7%) patients: 162 women, 11 men. Of these patients, 154 (89%) also had anti-Ro60/SSA positive abs., 103 (59.5%) anti-La/SSB abs., and 117 (67.6%) positive RF. Anaemia, leukopenia, lymphocytopenia and hypergammaglobulinemia, were significantly more frequent in patients with anti-Ro52 positive abs. The presence of anti-Ro52 abs. was significantly related to the development of lung fibrosis (OR 2.42, 95% CI 1.23–4.75, p=0.007), peripheral neuropathy (OR 2.53, 95% CI 1.1–5.95, p=0.022), arthritis (OR 1.95, 95% CI 1.2–3.35, p=0.016) and parotitis (OR 3.04, 95% CI 1.75–5.3, p Conclusions in our series most patients with anti-Ro52 positive antibodies had also anti-Ro60/SSA positive antibodies and met the AECG criteria. However, there were 13 patients with positive anti-Ro52 abs., which did not meet the AECG criteria. These patients showed similar characteristics to those with positive anti-Ro52 abs. and AECG criteria, and had more risk to develop peripheral neuropathy, lung fibrosis and lymphoma. Our results support that anti-Ro52 antibodies should be included in the diagnostic criteria for SS. Disclosure of Interest None declared

Background Giant cell arteritis (GCA) is a large-vessel vasculitis which can involve the aorta and/or its major branches. Tocilizumab (TCZ) seems to be effective in giant cell arteritis (GCA).1–4 Objectives Our aim was to assess if the clinical and analytical improvement yielded in patients with GCA treated with TCZ is accompanied by a reduction of the vascular inflammation evaluated by PET/CT. Methods Study of 36 patients who had a baseline and follow-up PET/CT from a multicenter series of 134 patients with GCA in treatment with TCZ. The evolution of the vascular involvement objectified by PET/CT was assessed. In addition clinical efficacy, analytical improvement (acute phase reactants) and the reduction of corticosteroid dose was studied. Results The 36 patients (28 women and 8 men) had an mean age of 69.83±8.66 years. After TCZ onset, a rapid and maintained clinical improvement was observed (table 1). In addition, during the first twenty-four months of follow-up, C-reactive protein decreased from 2.4 [0.9–6.8] to 0.1 [0.0–0.5] mg/dL and the erythrocyte sedimentation rate from 41.5 [16.7–58.5] to 4 [2–12.5] mm/1 st hour. On the other hand, the levels of haemoglobin experienced an increase from 12.3 [11.3–13.0] to 13.3 [13.0–13.9] g/dL. The median dose of prednisone decreased from 12.5 [9.4–26.2] to 0.0 [0.0–0.0] mg/day. However, the decrease in F18-fluordeoxyglucose uptake in the PET/CT study was not as evident. Conclusions Although TCZ seems to be an important therapeutic agent in the treatment of GCA, achieving a rapid and sustained clinical and analytical improvement, the decrease in vessel inflammation assessed by F18-fluordeoxyglucose uptake seems to take a slower course. References [1] Loricera J, et al. Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients. Semin Arthritis Rheum2015;44:717–723. [2] Loricera J, et al. Tocilizumab in refractory aortitis: Study on 16 patients and literature review. Clin Exp Rheumatol2014;32(3 Suppl 82):S79–89. [3] Loricera J, et al. Use of positron emission tomography (PET) for the diagnosis of large-vessel vasculitis. Rev Esp Med Nucl Imagen Mol2015;34:372–377. [4] Loricera J, Blanco R, Hernandez JL, et al. Tocilizumab in patients with Takayasu arteritis: A retrospective study and literature review. Clin Exp Rheumatol2016;34(3 Suppl 97):S44–53. Disclosure of Interest None declared

Background GCA is an inflamatory vasculitis affecting medium and large-sized arteries, that can result in arteritic anterior ischaemic optic neuropathy. C-reactive protein (CRP) level and erythocyte sedimentation rate (ESR) are usually elevated at GCA diagnosis, but inflammatory-marker negative disease does occur. Objectives To analyse the clinical and histological findings of patients with biopsy-proven GCA and negative inflammatory-markers at diagnosis. Methods multicenter-longitudinal retrospective study that included patients with biopsy-proven GCA recruited at 10 Hospitals from Spain (REVAS Study). Statistical analysis was performed using SPSS vs. 21. Results 418 patients: 290 (69.4%) females (ratio F/M: 2.3/1) were included. The mean age at diagnosis was 75.5±7 (53–92). The most frequent symptoms at diagnosis were recent onset headache (81%), toxic syndrome (47%) and rheumatic polymyalgia (44.5%). Jaw claudication, cranial hyperesthesia and amaurosis fugax were reported by 44.5%, 31.8% and 16.5% of patients, respectively. A total of 84 patients suffered permanent vision loss. Fourteen patients (3.3%) had normal ESR ( Conclusions typically patients with GCA present with elevated inflammatory-markers (ESR and CRP) at disease onset. However, a few percentages of patients (4%–5%) have normal ESR and CPR at diagnosis.1 In our series, 3.3% of patients had negative inflammatory-markers at diagnosis. These patients had fewer constitutional symptoms and more visual symptoms (amaurosis fugax and permanent visual loss) than patients with elevated ESR and/or CRP. Our result are similar to those published in the laiterature. Abnormal temporal arteries on physical examination may help to diagnosis Reference [1] Utility of Erithrocyte sedimentation rate and C-reactive protein for the diagnosis of Giant Cell arteritis. Semin Arthrithis Rheum2012;41:866–71 Disclosure of Interest None declared

Background GPA is a necrotizing granulomatous vasculitis associated with ANCA that usually involves ENT, lung and kidneys. ANCA are mostly directed against proteinase 3 (PR3), although in few cases are directed against myeloperoxidase (MPO) or negative. Objectives To analyse the phenotype, clinical course and outcome of patients with GPA according to ANCA positivity and specificity Methods multicenter retrospective-longitudinal study that included patients diagnosed with AAV between Jan 1995 and Jan 2016 in 21 Hospitals from Spain (REVAS-Study). We analysed the clinical characteristics, treatment and outcome, depending on the ANCA positivity and specificity. Statistical analysis was performed using SPSSvs.20 Results 221 patients with GPA were included:162 with PR3-ANCA, 36 with MPO-ANCA, and 23 with negative-ANCA. The mean-age at disease onset was higher in patients with MPO-ANCA (59.9□16.5 years) than in patients with PR3-ANCA (50.5□16.5) and negative ANCA (48□14.5), p=0.006. Compared to patients with PR3-ANCA, patients with MPO-ANCA presented a lower prevalence of toxic syndrome (42.9% vs. 55.6%, p=0.021), arthralgias (34.3% vs. 59.9%, p=0.008), arthritis (8.6% vs. 26.5%, p=0.026), pulmonary involvement (cavitated/infiltrated nodules, p=0.007 and p=0.05), and anaemia (57.1% vs. 77.8%, p=0.05). Renal disease was less severe in patients with MPO-ANCA (creatinine ≥1.58 mg/dL 14.3% vs. 30.4%,p=0.04). Subglottic stenosis and sensoryneural deafness were more frequent in patients with MPO-ANCA (20% vs. 6.8%, p=0.05% and 34.3% vs. 18%, p=0.03). The mean BVAS at baseline was lower in patients with MPO-ANCA (16.3□8.8) and negative ANCA (12.5□6.7) than in patients with PR3-ANCA (19.6□8.9), p=0.029. Patients with negative ANCA had less frequently toxic syndrome, fever, arthritis, subglottic stenosis, kidney disease, and peripheral neuropathy, and more frequently orbital masses. Disease relapses were less frequent in patients with MPO-ANCA than in patients with PR3-ANCA (37.1% vs. 48.8%, p=0.04), but more frequent than in patients with negative ANCA (20.8%), p=0.002. Patients with MPO-ANCA and negative ANCA received less frequently oral cyclophosphamide. No significant differences were found related to death in patients with MPO-ANCA and PR3-ANCA. Patients with negative ANCA had the lower mortality Conclusions A small percentage of patients with GPA present MPO-ANCA or negative ANCA. In our series, patients with MPO-ANCA were older at the disease onset, presented limited or less severe organic disease than patients with PR3-ANCA, lower percentage of relapses and lower requirement of aggressive therapies. Patients with negative ANCA had the best prognosis. Our findings are similar to those recently published,1 although our patients with MPO-ANCA were older. Classification of GPA patients considering ANCA specificity can improve the treatment stratification and reduce adverse events. Reference [1] Schirmer JH, et al. Myeloperoxidase-antineutrophil-cytoplasmic-antibody (ANCA) positive Granulomatosis with polyangiitis.A clinically distinct subset of ANCA-assocaited vasculitis. Arthritis Rheum2016;68:2953–63 Disclosure of Interest None declared

Background Epidemiological data suggest that some viruses may be linked to the development of autoimmunity. Objectives The objective of this work was to determine the presence of HHV-8 viral DNA in whole blood from patients suffering from different systemic autoimmune diseases (SAD). We also aimed at testing the prevalence of patients showing antibodies against an HHV-8 orfK8.1 peptide. Study design Two hundred and eighty SAD patients and 50 healthy blood donor controls were included. Molecular analyses were performed by nested PCR from DNA obtained from whole blood and an enzyme immunoassay was developed in order to test for the presence of antibodies directed against a synthetic peptide derived from the HHV-8 orfK8.1 protein. Results Only 2 out of the 280 samples analyzed yielded the specific HHV-8 PCR product. Antibodies against orfK8.1 were detected in 2 SLE patients, 1 patient suffering from Sjogren's syndrome and 2 patients with vasculitis. Conclusions We conclude that HHV-8 is usually not present in blood neither from autoimmune patients nor from healthy controls. Furthermore, HHV-8 antibodies against the HHV-8 orfK8.1 peptide were rarely detected. It leads us to infer that HHV-8 is not involved on the development of these disorders. It does not rule out the possibility that other environmental and microbiological triggers may account for their etiopathogenesis.

Background GPA is a necrotizing systemic vasculitis that usually involves ENT, lung and kidneys. Neurological manifestations appear in 25–50% of patients, usually involving peripheral nervous system. CNS involvement, has been reported in only 7–11% of cases Objectives to describe the clinical features and outcome of patients with GPA and CNS involvement in a large series of patients with AAV Methods multicenter retrospective-longitudinal study that encompassed patients diagnosed with AAV between Jan 1995 and Nov 2014 in 21 Centres from Spain (REVAS Study). Statistical anlysis was performed using SSPS vs20 package Results 455 patients (188 GPA, 167 MPA and 100 EGPA) were included. Mean age at diagnosis was 55.7±17.2y. ANCA were positive in 86.8% of cases (35.8% C-ANCA, 51% P-ANCA). Median time to diagnosis was 4 weeks (IQR 10). Median follow-up time was 80 months (IQR 105). Neurological involvement was documented in 156 (34.5%) patients, but only 33 (7.3%) presented CNS involvement at disease onset. From those patients, 20 (60.6%) had GPA. Mean age at diagnosis of patients with GPA and CNS involvement was 51.1±16.7y. ANCA were positive in all cases (15 C-ANCA-PR3, 5 P-ANCA-MPO). Headache was the main neurological symptom (60%) followed by sensory (45%) and motor impairment (35%). MRI and/or angio-CT scan were performed in all cases. Cerebral ischaemic lesions were observed in 10 patients, and granulomatous lesions in 9, including pachymeningitis (n=6), spinal cord pachymeningitis (n=2) and isolated granulomatous lesions (n=1). Lumbar puncture was performed in 8 (40%) patients and revealed CSF abnormalities in 70. Diagnosis was confirmed by meningeal biopsy (n=2), ENT biopsies (n=5) and renal biopsy (n=2) in patients with CNS granulomatous lesions, and by renal, pulmonary or peripheral nerve biopsy in patients with CNS ischemic lesions. Headache was predominant in patients with granulomatous lesions, while sensory and motor impairment were predominant in patients with ischemic lesions. Mean BVAS at disease onset was 29.2±9.7, significantly higher than in GPA total cohort (18.2±9.2). Renal involvement was more common in patients with ischaemic lesions than in those with granulomatous (80% vs. 40%, p Conclusions Patients with GPA and CNS involvement have more severe disease at presentation and more treatment-related side effects than patients without CNS involvement. Long-term neurological sequelae are more frequent in patients with ischaemic lesions and spinal cord pachymeningitis Disclosure of Interest None declared

Background GCA is the most common systemic vasculitis in elderly people. It is characterized by granulomatous involvement of the major branches of the aorta with predilection for the temporal arteries. Headache is the most frequent initial complaint, and permanent visual loss the most feared complication. Objectives to describe the initial manifestations and outcome of CGA in octogenarian patients, and to investigate if there are some differences compared to younger patients Methods demographic, clinical and histological features, treatment and outcome of all patients with biopsy-proven GCA recruited at 11 different Hospitals from Spain (REVAS Study) were analysed. Statistical analysis was performed using SPSS vs. 20 Results among the 418 patients included in the study, 180 (27.5%) were older than 80 y at disease onset (mean age 83.77±3.1, range 80–92y). Cardiovascular risk factors (hypertension, hypercholesterolemia, diabetes) were more prevalent in octogenarian patients than in younger (73% vs. 50%, p=0.018). Headache was the most frequent initial complaint (78.5%), followed by polymyalgia rheumatica (49.6%), jaw claudication (48.7%) and toxic syndrome (43.5%). A total of 28 (24.35%) patients suffered permanent visual loss, due to anterior ischemic optic ischemic neuropathy (n=26) or central retina vein thrombosis (n=4). When compared with younger patients, neither headache, nor jaw claudication, nor scalp tenderness and polymyalgia, were more common in octogenarian patients. Only fever was less common in patients >80 y at diagnosis than in younger (27.7% vs. 72.3%, p=0.006), and permanent visual loss was most prevalent among octogenarian patients (24.3% vs. 15.7%, OR 1.73, 95CI 1.1–2.9, p=0.04). We found an inverse correlation between fever and permanent visual loss (p=0.001). Blindness was significantly correlated with jaw claudication (p=0.006) and amaurosis fugax (p=0.001). We did not found any significant correlation between blindness and vascular risk factors. Regarding to LAB, ESR was higher in octogenarian patients (p=0.006) as well as thrombocytosis >400.000 platelets/mm (p=0.026). No differences were found related to anaemia prevalence. Inflammatory infiltrate with lumen occlusion and giant cells were significantly more prevalent in temporal artery biopsies from patients with permanent bilateral visual loss (p=0.007 and p=0.01, respectively). No differences were found related to treatment. All patients received oral prednisone at tapering dosage, 85.9% calcium and vitamin D supplementation, and 60% bifosfonates. We did not found differences related to treatment-side effects (osteoporotic fracture, diabetes, infections) between octogenarian patients and the younger. Conclusions octogenarian patients with GCA have an increased risk of developing permanent visual compared to younger patients. The presence of jaw claudication and amaurosis fugax must prompt to initiate corticosteroid treatment quickly. No differences were found related to treatment side effects in octogenarian patients. Disclosure of Interest None declared

Background There is a lack of strong evidence on IgG4-related disease (IgG4-RD) treatment. There is only one clinical trial published, supporting the use of rituximab in American patients. Objectives To describe the treatments used in a series of patients diagnosed with IgG4-RD in Spain and to review the outcomes. Methods Clinical data were obtained from the Spanish Registry of IgG4-RD from October 2013 to January 2016, including 14 centers. Outcomes were assessed by a self-made response scale and the IgG4 responder index (RI). We categorized the outcomes as a total response (disappearance of the pseudotumoral lesions and absence of symptoms), partial response ( Results Sixty-eight patients were included. Twenty-six (38%) were females, mean age 53.4 years. Thirty-six patients (52.9%) had systemic IgG4-RD involving >1 tissue. The most commonly involved tissues were: retroperitoneum (33%), orbital pseudotumor (28%), and maxillary and paranasal sinuses (24%). The main treatments used were: steroids (90%), surgery (45%) and azathioprine (19%). All treatments were successful in achieving complete or partial response. The mean pre and post-treatment RI values were 6.7 (SD 4.6) and 1.9 (SD 2.6) respectively. There were no differences between systemic and non-systemic disease regarding the chosen treatments and the outcomes. The combination azathioprine-steroids was used in 12 patients. Fourteen percent of them relapsed (considering relapse as an increase of the inflammation, mass size or reappearance of symptoms, since the first month after the treatment withdrawal). The treatment failed in 28.6% of them. The combination steroids-rituximab was indicated in 6 patients, showing no relapses and 1 treatment failure. The majority of patients treated with azathioprine or rituximab combined with steroids had a systemic disease (6.6 and 80%, respectively). Nearby all of them had already failed other previous treatments. Conclusions In our series, IgG4-RD has been treated with a myriad of drugs and procedures. The outcomes have been acceptable but the disease tended to relapse (21%) and the treatment failures were common (27%), probably due to the lack of well-defined treatment schemes supported by solid studies. Steroids were still the cornerstone of the treatment. Rituximab results were promising in our study but the number of patients was limited. Azathioprine, in combination with steroids, may be an accessible alternative treatment for IgG4-RD that should be explored. The RI correlated with the treatment outcomes and will have an important role monitoring future studies on IgG4-RD therapies. Disclosure of Interest None declared

ObjectivesTo analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.MethodsThe Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed.ResultsWe included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69).ConclusionsThis study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis.

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 18 mars 2017

Cutaneous complications associated with decorative tattooing are well known. However, the inhibition of a purpuric reaction by a tattoo is a fact that, as far as the authors know, has not been described before, fitting the definition of a ‘sparing phenomenon', the absence of manifesting a particular skin disease in an area previously affected by another condition. From the clinical observation of purpuric lesions apparently inhibited by a tattoo in a 26-year-old patient, we performed an exact binomial test on the observed and expected proportion of purpuric lesions inside (0%, 95% confidence interval, CI, 0-2.6%) and outside (100%, 95% CI 97.4-100%) the tattooed skin, demonstrating a nonrandom distribution respecting the tattooed area (p < 0.001) and identifying the composition of the ink used in the tattoo (color pigment, glycerine, Hamamelis virginiana extract, water and alcohol). Moreover, we reviewed the cases of sparing phenomenon described in the literature. In conclusion this is the first report of a sparing phenomenon of purpuric lesions over tattooed skin.

ObjectiveTo develop and validate ClinESSDAI (Clinical European League Against Rheumatism Sjögren's Syndrome Disease Activity Index), ie, ESSDAI without the biological domain.Patients and methodsThe 702 fictive vignettes derived from 96 real cases of primary Sjögren's syndrome of the ESSDAI development study were used. As for ESSDAI development, the physician assessment of disease activity (0–10 scale) was used as the ‘gold standard’ in a multivariate model for weighting domains, after removing the biological domain. The reliability, assessed by intraclass correlation coefficient (ICC) between ClinESSDAI and ESSDAI, explored if ClinESSDAI was equivalent to ESSDAI. Its psychometric (ie, measurement) properties were compared with that of ESSDAI in an independent cohort. Also, its use was evaluated on data of two clinical trials.ResultsIn multivariate modelling, all 11 domains remained significantly associated with disease activity, with slight modifications of some domain weights. Reliability between clinESSDAI and ESSDAI was excellent (ICC=0.98 and 0.99). Psychometric properties of clinESSDAI, disease activity levels and minimal clinically important improvement thresholds and its ability to detect change over time in clinical trials were very close to that of ESSDAI.ConclusionsClinESSDAI appears valid and very close to the original ESSDAI. This score provides an accurate evaluation of disease activity independent of B-cell biomarkers. It could be used in various circumstances: (i) in biological/clinical studies to avoid data collinearity, (ii) in clinical trials, as secondary endpoint, to detect change independent of biological effect of the drug, (iii) in clinical practice to assess disease activity for visits where immunological tests have not been done.

Cerebrovascular accidents (CVAs) and multi-infarct dementia have rarely been reported as presenting symptoms of giant cell arteritis (GCA), although 3%-4% of patients with GCA may present with CVAs during the course of the disease. We describe 7 patients with biopsy-proven GCA who presented with stroke or multi-infarct dementia. Most of them had other symptoms of GCA when the disease began that were misdiagnosed or not noticed. The internal carotid arteries were involved in 4 patients and the vertebrobasilar arteries in 3, with bilateral vertebral artery occlusion in 1. Small cerebral infarction foci on cranial computed tomography (CT) scan and magnetic resonance imaging (MRI) were found in 5 cases, and cerebellar infarction, in 2. MR angiography showed intracranial arteritis in 4 cases. Treatment with glucocorticoids and adjunctive antiplatelet or anticoagulant therapy was given in all cases, with neurologic improvement in 5. Two patients died. Necropsy demonstrated generalized GCA involving the medium and small cerebral vessels in 1 case. Central nervous system involvement is a rare complication in GCA but is important to recognize, as it can be reversible if diagnosed and treated promptly. Suspicion should arise in elderly patients suffering from strokes with a quickly progressing stepwise course and associated headache, fever, or inflammatory syndrome. In these cases, temporal artery biopsy should be performed without delay. Early diagnosis of GCA and immediate initiation of corticosteroid treatment may prevent progressive deterioration and death. Additional antiplatelet or anticoagulant therapy should be evaluated according to the individual risk and benefit to the patient under care.

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.

The objective of this study was to assess the prevalence, clinical, histological and immunological characteristics, and the long-term outcome of polymyositis-(PM) and dermatomyositis-(DM) associated lung disease, and to define subgroups of lung-associated inflammatory myopathies. This retrospective study included 81 consecutive patients diagnosed with PM/DM. Pulmonary involvement was systematically investigated in relation to clinical symptoms by chest radiography, high resolution computed tomography and pulmonary function testing. Anti-synthetase autoantibodies (ASA) were analysed by ELISAandconfirmedbyproteinandRNA immunoprecipitation methods. Statistical analyses were done with the Student t-test and Fisher exact test. Cumulative survival probabilities were estimated by the Kaplan-Meier method and Cox regression analysis. Fifty patients (61%) presented pulmonary involvement. Thirty-two (39%) had interstitial lung disease and five of them had devastating acute interstitial pneumonia with pneumomediastinum and an unfavorable prognosis. Histology showed diffuse alveolar damage in this subgroup and ASA were negative. Eighteen patients (22%) presented restrictive myopathic lung disease; in three of them respiratory muscles could not maintain ventilation. ASA were positive in 17 of the 50 patients (34%) and were significantly associated with interstitial lung disease (OR: 4.5 [95% CI: 1.3-15.3]), arthritis (OR: 6.0 [95% CI: 1.3-29.2]) and ‘mechanic hands’ (OR: 8.5 [95% CI: 1.7-41.4]); the presence of these autoantibodies did not imply worse survival prognosis. We concluded that clinical and immunological characteristics allowed the grouping of patients into different types of PM/DM lung-associated disease. Presence of ASA did not affect survival. ASA-negative patients with acute interstitial pneumonitis and pneumomediastinum had an unfavorable prognosis.

Background: Compelling arguments exist for a role of infectious agent in giant cell arteritis (GCA). Parvovirus B19 and several herpesviruses have focussed the attention in recent years, but the few studies to date have yielded inconsistent results. Objectives: To study the relationship between the presence of parvovirus B19 DNA or major known herpesviruses and the histopathological features of GCA. Study design: Between January 1997 and March 2002, 147 consecutive temporal artery biopsies were performed in our center because of a clinical suspicion of GCA. Using polymerase chain reaction (PCR) procedures validated by the World Health Organization and employed routinely by our laboratory, we examined the paraffin-embedded specimens for DNA from parvovirus B19, herpes simplex viruses (HSV) 1 and 2, Epstein–Barr virus (EBV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV-6). We investigated positive results further with immunohistochemistry studies. Results: Fifty of the 147 temporal artery biopsies (34%) showed histological features of GCA. Three biopsies (2.5%) were initially PCR positive for parvovirus B19. None of the herpesvirus PCR assays were positive. Upon repeat testing by both PCR and immunohistochemistry, none of the three initially positive parvovirus B19 assays were confirmed. The results of both positive and negative control assays in these studies validated these findings. We confirmed the presence of amplifiable DNA in the temporal artery biopsy specimens using PCR primers for beta-globin and indoleamine 2,3-dioxygenase (IDO). Conclusions: The results of our study do not support a role in the etiopathogenesis of GCA for either parvovirus B19 or any of these six herpesviruses.

International audience; Objective. The aim of this study was to describe the presentation and outcomes of patients with granulomatosis with polyangiitis (GPA) presenting with CNS involvement.Methods. Patients were included in this nationwide retrospective study if they had GPA according to ACR criteria and/or the European Medicines Agency algorithm and CNS involvement.Results. Thirty-five patients were included in the study. CNS involvement was observed in 51% of patients at GPA diagnosis. Headache (66%) was the main symptom, followed by sensory (43%) and motor impairment (31%). CNS involvement was characterized by pachymeningitis in 20, cerebral ischaemic lesions in 15 and haemorrhagic lesions in 2, with hypophyseal involvement in 2 patients. According to the clinical–radiological presentation, we distinguished granulomatous (G-CNS) and vasculitic (V-CNS) phenotypes. G-CNS patients more frequently had headaches, while V-CNS patients more frequently had motor impairment and renal involvement. Induction therapy produced clinical responses in 86% of patients. Baseline modified Rankin scale was higher for V-CNS than G-CNS patients (3 vs 2, P = 0.002). Initial spinal cord pachymeningitis was significantly associated with the need for a new induction regimen for relapsing/refractory disease ( P = 0.01). Long-term neurological sequelae were noted in 51% of patients, including 35% with G-CNS and 69% with V-CNS ( P = 0.08). Neurological sequelae were mainly noted in cases of spinal cord pachymeningitis (100%) and ischaemic or haemorrhagic lesions (73%).Conclusion. The clinical–radiological phenotype distinguished different long-term outcomes in patients with GPA and CNS involvement. Long-term neurological sequelae persisted in half of patients, mainly those with spinal cord pachymeningitis and vasculitic lesions.