240 results on '"Guido Valesini"'
Search Results
2. Subclinical atherosclerosis in systemic sclerosis: Different risk profiles among patients according to clinical manifestations
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Nicoletta Iannace, Massimiliano Vasile, Alessia Carboni, Carlotta Angelelli, A Scarno, I. Sciarra, Katia Stefanantoni, Valeria Riccieri, and Guido Valesini
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Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Brachial Artery ,Carotid Artery, Common ,Diastole ,Carotid Intima-Media Thickness ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Risk Factors ,Internal medicine ,medicine.artery ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Common carotid artery ,Brachial artery ,Pathological ,Aged ,Subclinical infection ,030203 arthritis & rheumatology ,Scleroderma, Systemic ,Framingham Risk Score ,business.industry ,Odds ratio ,Middle Aged ,Atherosclerosis ,Plaque, Atherosclerotic ,Vasodilation ,medicine.anatomical_structure ,Ventricle ,Case-Control Studies ,Asymptomatic Diseases ,Cardiology ,Female ,business - Abstract
INTRODUCTION Like other autoimmune diseases, systemic sclerosis (SSc) has been described to be associated with accelerated atherosclerosis (ATS). Before clinical manifestations of cardiovascular disease (CVD) occur, subclinical ATS can be investigated in different ways. AIM To evaluate the presence of subclinical ATS in a group of patients with SSc, and to identify different risk profiles among patients. METHODS Subclinical ATS was reviewed in 43 SSc patients and 27 healthy controls, using 2 methods: carotid ultrasound and flow mediated dilation (FMD) of the brachial artery. RESULTS Plaques were statistically more frequent in SSc patients than in controls (65% vs 30%, P = .006); intima-media thickness of common carotid artery (CCA-IMT) resulted in statistically higher (median value 0.8 mm vs 0.55 mm; P
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- 2020
3. Usefulness of composite indices in the assessment of joint involvement in systemic lupus erythematosus patients: correlation with ultrasonographic score
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Laura Massaro, Francesca Romana Spinelli, Enrica Cipriano, Carlo Perricone, Fabrizio Conti, Fulvia Ceccarelli, Guido Valesini, F. Natalucci, and Cristiano Alessandri
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Adult ,Male ,musculoskeletal diseases ,0301 basic medicine ,medicine.medical_specialty ,Severity of Illness Index ,Correlation ,Disease activity ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,Rheumatology ,Reference Values ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,030203 arthritis & rheumatology ,Synovitis ,business.industry ,Arthritis ,Ultrasonography, Doppler ,ultrasonography ,Middle Aged ,medicine.disease ,Arthralgia ,disease activity ,joint involvement ,030104 developmental biology ,Joint involvement ,Rheumatoid arthritis ,Female ,Joints ,Ultrasonography ,business - Abstract
Specific indices are not available to evaluate systemic lupus erythematosus (SLE) joint involvement; indeed, the application of indices validated for rheumatoid arthritis has been suggested. We evaluated the usefulness of organ specific composite indices, i.e. the Disease Activity Score on 28 joints (DAS28), Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and the ratio of swollen to tender joints (STR), to assess SLE joint activity by analyzing the correlation between these indices and ultrasonography (US) inflammatory status. We evaluated SLE patients with arthralgia and/or arthritis: the above-mentioned indices were calculated and the SLE Disease Activity Index 2000 (SLEDAI-2k) was applied to assess global disease activity. US of I–V metacarpophalangeal, I–V proximal interphalangeal, wrist, and knee bilateral was performed. Synovial effusion/hypertrophy and power Doppler findings were scored according to a semi-quantitative scale (0–3) to obtain an inflammatory total score (0–216). One hundred and six patients (M/F 7/99, median age 49.5 years (IQR 17.0), median disease duration 8.5 years (IQR 17.0)) were enrolled. We identified a positive correlation between US score and DAS28-CRP ( r = 0.3, p = 0.007), STR ( r = 0.42, p = 0.0005), SDAI ( r = 0.33, p = 0.02), CDAI ( r = 0.29, p = 0.03); US score reflected different levels of clinimetric joint activity. In conclusion, we suggest the ability of composite indices in detecting SLE joint inflammation and their possible real-life use.
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- 2019
4. Potential role of platelets for atherosclerotic events in rheumatoid arthritis
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Anna C hiara Di Lollo, Elisabetta Straface, Walter Malorni, Manuela Di Franco, Rosa Vona, Cristina Iannuccelli, Lucrezia Gambardella, and Guido Valesini
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0301 basic medicine ,rheumatoid arthritis ,medicine.medical_specialty ,Inflammation ,Disease ,030204 cardiovascular system & hematology ,medicine.disease_cause ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,platelet activation ,oxidative stress ,Platelet ,Platelet activation ,Research Articles ,Whole blood ,business.industry ,medicine.disease ,Adenosine diphosphate ,030104 developmental biology ,chemistry ,inflammation ,platelet aggregation ,Rheumatoid arthritis ,medicine.symptom ,atherosclerosis ,business ,Oxidative stress ,Research Article - Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease with increased risk of cardiovascular events and mortality that can be attributed to accelerated atherosclerosis. This pilot study aimed to investigate if changes in blood parameters were compatible with atherosclerotic events in RA patients. To this aim, 45 RA women (aged more than 18 years), and 25 age and gender-matched healthy donors (HD) were included. Biomarkers of oxidative stress, platelet activation and platelet aggregation were analysed in RA patients at baseline and after six months of treatment with disease modifying anti-rheumatic drugs (DMARDs). Flow cytometry analysis revealed that ca. 4% of platelets was in activated state (evaluated in term of Annexin V and PAC-1 positivity) in RA patients at baseline, and that the 76% of platelets displayed mitochondrial hyperpolarization. Moreover, platelets from RA patients at baseline aggregated more than those from HD after whole blood treatment with adenosine diphosphate. Interestingly, platelet aggregation in patients at baseline positively correlated with disease activity measured by DAS28 score. After six months of treatment with DMARDs, platelet activation and platelet aggregation reached values comparable to those of HD. Our preliminary data suggest that platelets might play an active role in the atherosclerosis occurring in RA patients.
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- 2018
5. Immediate treatment with tumour necrosis factor inhibitors in synthetic disease-modifying anti-rheumatic drugs-naïve patients with rheumatoid arthritis: results of a modified Italian Expert Consensus
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Pier Luigi Meroni, Alessandra Bortoluzzi, Guido Valesini, Laura Bazzichi, Bruno Frediani, Andrea Doria, Marcello Govoni, Giuseppe Paolazzi, Antonella Afeltra, and Salvatore D'Angelo
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medicine.medical_specialty ,Consensus ,Antirheumatic Agents ,Arthritis, Rheumatoid ,Humans ,Italy ,Treatment Outcome ,Tumor Necrosis Factor-alpha ,Rheumatology ,Pharmacology (medical) ,medicine.medical_treatment ,Population ,MEDLINE ,Disease ,NO ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Rheumatoid ,Internal medicine ,medicine ,030212 general & internal medicine ,Intensive care medicine ,education ,030203 arthritis & rheumatology ,education.field_of_study ,business.industry ,Arthritis ,medicine.disease ,TNF inhibitor ,Systematic review ,Rheumatoid arthritis ,business - Abstract
Objective To establish clinical consensus for the optimal placement of TNF inhibitor (TNFi) in DMARDs-naive RA patients. Methods The steering group was composed of 15 Italian rheumatologists expert in the field of RA, who proposed and selected by consensus the clinically relevant questions on the role of TNFi treatment in DMARDs-naive RA patients. The question was rephrased according to the population, intervention, comparison and outcome statement. The available scientific evidence on this topic were collected by updating the systematic literature reviews used for the EULAR 2013 recommendations up to January 2016. The aspects evaluated in the studies concerned clinical efficacy, radiographic structural damage and safety. After the systematic literature review the expert panel formulated a consensus statement, and a modified Delphi panel evaluated the level of agreement between panellists (strength of recommendation). Results From a total of 1080 records we have included 6 studies, 2 randomized clinical trials and 4 open-label extension trials. Evidence from publications generated three statements for the final consensus document. The systematic literature review and the consensus statements developed showed that, for patients with early RA and in the presence of a treat-to-target strategy, the immediate use of anti-TNFi compared with an early (within 12 weeks) step-up to anti-TNF therapy did not confer a significant advantage regarding clinical, functional and radiographic outcomes. Conclusion The most appropriate placement of the TNFi therapy in the treatment algorithm of early RA still remains a challenging clinical question that needs to be further addressed.
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- 2018
6. Genetic diversity of staphylococcus aureus influences disease phenotype of systemic lupus erythematosus
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Francesca Antonelli, Giancarlo Iaiani, Alessandra Lo Presti, Massimo Ciccozzi, C. Garufi, Francesca Romana Spinelli, Alessandra Giordano, Lucia Florio, Marina De Cesaris, Cristiano Alessandri, Giulio Olivieri, Luigino Amori, Silvia Angeletti, Carlo Perricone, Fabrizio Conti, Fulvia Ceccarelli, and Guido Valesini
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0301 basic medicine ,Male ,staphylococcus aureus ,medicine.medical_specialty ,disease phenotype ,medicine.disease_cause ,Gastroenterology ,Pathogenesis ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,systemic lupus erythematosus ,Interquartile range ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Clade ,Correlation of Data ,Phylogeny ,030203 arthritis & rheumatology ,Genetic diversity ,Molecular epidemiology ,Phylogenetic tree ,business.industry ,pathogenesis ,phylogenetic analysis ,Immunity ,Patient Acuity ,Genetic Variation ,Middle Aged ,Staphylococcal Infections ,Methicillin-resistant Staphylococcus aureus ,030104 developmental biology ,Italy ,Staphylococcus aureus ,Genes, Bacterial ,Female ,Joint Diseases ,Nasal Cavity ,Symptom Assessment ,business - Abstract
Objective We investigated the genetic diversity, molecular epidemiology and evolutionary dynamics of Staphylococcus aureus (SA) isolated from SLE patients by means of phylogenetic analysis. Methods Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of the translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate relationships and to assess significant clades. Selective pressure analysis was used to investigate the evolution of the SA tuf gene. The gene sequences from non-SLE individuals, downloaded from the GenBank database, were compared through phylogenetic analysis with the tuf gene from SLE patients. Results We enrolled 118 patients [M/F 10/108; median (interquartile range (IQR)) age 45.5 (13.2) years; median (IQR) disease duration 120 (144) months]. Twenty-four patients (20.3%) were SA carriers (SA+), three of them MRSA. SA+ SLE showed significantly higher SLEDAI-2k values [SA+: median (IQR) 2 (3.75); SA−: 0 (2); P = 0.04]. The phylogenetic analysis, restricted to 21 non-MRSA SA+, revealed a statistically supported larger clade (A, n = 17) and a smaller one (B, n = 4). Patients located in clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P Conclusion We suggest a possible role of SA nasal carriage status in SLE disease activity. Moreover, our findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.
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- 2021
7. Pregnancy outcome in systemic lupus erythematosus patients. a monocentric cohort analysis
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Carlo Perricone, V. A. Pacucci, Valeria Orefice, Aikaterina Selntigia, Fabrizio Conti, Francesca Romana Spinelli, Fulvia Ceccarelli, Guido Valesini, Carmelo Pirone, Roberto Brunelli, Simona Truglia, Giuseppina Perrone, Paola Galoppi, and Cristiano Alessandri
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Adult ,medicine.medical_specialty ,SLE ,counselling ,multidisciplinary approach ,outcome ,pregnancy ,Context (language use) ,Disease ,snRNP Core Proteins ,Cohort Studies ,Rheumatology ,Internal medicine ,medicine ,Humans ,Lupus Erythematosus, Systemic ,Pharmacology (medical) ,Autoimmune disease ,Pregnancy ,Systemic lupus erythematosus ,Obstetrics ,business.industry ,Infant, Newborn ,Pregnancy Outcome ,DNA ,Ribonucleoproteins, Small Nuclear ,medicine.disease ,Pregnancy Complications ,Antibodies, Antinuclear ,Case-Control Studies ,Infant, Small for Gestational Age ,Small for gestational age ,Female ,business ,Cohort study - Abstract
Objective SLE is an autoimmune disease, mainly affecting women of childbearing age, with possible impact on pregnancy. In this study, we evaluated pregnancy outcomes in all pregnant patients affected by SLE, followed in the context of a rheumatology/gynaecology multi-disciplinary team. Methods Since 2008, we evaluated 70 consecutive pregnancies occurring in 50 SLE patients referring to the Lupus Clinic of Sapienza University of Rome; as controls we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases. Results By comparing SLE patients and controls, we did not find differences in terms of pregnancy outcomes, except for the occurrence of small for gestational age, which was significantly higher in the SLE group (22.8% vs 11%, P =0.003). Small for gestational age was associated with the positivity for anti-dsDNA, anti-Sm and anti-RNP (P =0.009, P =0.02, P =0.002, respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium periods (44.3%). Flare during pregnancy was associated with anti-SSA (P =0.02), while puerperium relapse with previous MMF treatment (P =0.01) and haematological flare during pregnancy (P =0.03). Conclusion The present study confirms how pre-gestational counselling and a multi-disciplinary approach could result in positive pregnancy outcomes for SLE patients. The high percentage of disease relapse justifies even more the need for multi-disciplinary management.
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- 2021
8. IgM-Rheumatoid factor confers primary resistance to anti-PD-1 immunotherapies in NSCLC patients by reducing CD137+T-cells
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Marianna Nuti, Paolo Marchetti, Ilaria Grazia Zizzari, Hassan Rahimi, Fulvia Ceccarelli, Alessio Ugolini, Guido Valesini, Tania Colasanti, Fabrizio Conti, Andrea Botticelli, Aurelia Rughetti, and Lidia Strigari
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0301 basic medicine ,Oncology ,Male ,Chemokine ,Lung Neoplasms ,Survival ,T-Lymphocytes ,Programmed Cell Death 1 Receptor ,lcsh:Medicine ,NSCLC ,Lymphocyte Activation ,cd137(+) t-cells ,igm-rheumatoid factor ,nsclc ,prognostic biomarker ,survival ,anti-pd-1 icis ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Molecular Targeted Therapy ,Immune Checkpoint Inhibitors ,lcsh:R5-920 ,education.field_of_study ,biology ,CD137 ,General Medicine ,Middle Aged ,Prognosis ,030220 oncology & carcinogenesis ,IgM-rheumatoid factor ,Disease Progression ,Female ,lcsh:Medicine (General) ,Research Paper ,medicine.medical_specialty ,anti-PD-1 ICIs ,Prognostic biomarker ,Population ,CD137+ T-cells ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Tumor Necrosis Factor Receptor Superfamily, Member 9 ,Immune system ,In vivo ,Rheumatoid Factor ,Internal medicine ,medicine ,Humans ,education ,Survival rate ,Aged ,Retrospective Studies ,business.industry ,lcsh:R ,CCL19 ,Autoantibody ,030104 developmental biology ,Immunoglobulin M ,Drug Resistance, Neoplasm ,biology.protein ,business - Abstract
Background ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137+T-cells are largely known to be the anti-tumor activated effector cells, but they have never been associated with the response to immunotherapies. Methods Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant'Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated. Findings IgM-RF in NSCLC patient sera strongly predicted the development of early progression to ICIs. Also, a significant reduction of progression-free survival rate in anti-PD-1 treated patients could be identified when patients were stratified based on IgM-RF positivity and titers. IgM-RF bound preferentially circulating naive and central memory T-cells and a significant reduction of CD137+ anti-tumor T effector cells was found in IgM-RF positive patients. In addition, a higher percentage of CD137+T-cells in peripheral blood of NSCLC patients at baseline resulted as a strong independent prognostic factor for a better outcome in terms of PFS and OS after the anti-PD-1 treatment. Furthermore, T-cells exposed to IgM-RF showed a robust defect in their migratory ability in response to CCL19 chemokine. Interpretation In this study we showed that serum IgM-RF can be regarded as predictive factor for the development of early progression and prognostic factor of a reduced progression-free survival and overall-survival in anti-PD-1 treated NSCLC patients. The ability of IgM-RF to bind naive and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137+ T-cells population that may cause a non-effectiveness of these T-cells targeting drugs. Fundings AIRC, MIUR and Sapienza University of Rome.
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- 2020
9. An exploratory cross-sectional study of subclinical vascular damage in patients with polymyalgia rheumatica
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Francesco Fedele, C Sestili, Iolanda Maria Rutigliano, Fabrizio Conti, Fulvia Ceccarelli, Valeria Silvestri, Guido Valesini, Bruno Gossetti, Francesco Ciciarello, Antonio Sili Scavalli, Giuseppe La Torre, Valeria Riccieri, Francesca Romana Spinelli, Roberta Priori, Paola Sessa, Luciano Agati, Cristiano Alessandri, Alessio Altobelli, Manuela Di Franco, Rossana Scrivo, and Cristiana Barbati
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Leptin ,Male ,cardiovascular risk factors ,Vasculitis syndromes ,Comorbidity ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,polymyalgia rheumatica ,0302 clinical medicine ,color doppler ultrasoun ,cavi ,imt ,adipocytokines ,Risk Factors ,Resistin ,Aorta, Abdominal ,Ultrasonography, Doppler, Color ,Subclinical infection ,Aged, 80 and over ,education.field_of_study ,Multidisciplinary ,Smoking ,Middle Aged ,Cardiovascular Diseases ,Cardiology ,Medicine ,Female ,Adiponectin ,musculoskeletal diseases ,medicine.medical_specialty ,Carotid Artery, Common ,Science ,education ,Hypercholesterolemia ,Population ,Adipokine ,Article ,Polymyalgia rheumatica ,Peripheral Arterial Disease ,03 medical and health sciences ,Vascular Stiffness ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Ankle Brachial Index ,Aged ,030203 arthritis & rheumatology ,business.industry ,Overweight ,medicine.disease ,Stenosis ,Cross-Sectional Studies ,Case-Control Studies ,Arterial stiffness ,business - Abstract
The aim of the study was to investigate the presence of subclinical vascular damage in polymyalgia rheumatica (PMR). We enrolled PMR patients having major cardiovascular risk factors (MCVRF) and, as controls, patients with MCVRF. All underwent: color Doppler ultrasound to evaluate the common carotid intima-media thickness (IMT), the anterior–posterior abdominal aortic diameter (APAD), and the prevalence of carotid artery stenosis; the cardio-ankle vascular index (CAVI) to measure arterial stiffness together with the ankle-brachial index (ABI) to investigate the presence of lower-extremity peripheral arterial disease. Finally, we measured the serum levels of adipocytokines implicated in vascular dysfunction. As a result, 48 PMR and 56 MCVRF patients were included. An increase of IMT (1.07/0.8–1.2 vs 0.8/0.8–1.05; p = 0.0001), CAVI (8.7/7.8–9.3 vs 7.6/6.9–7.8; p 2 = 0.845 and r2 = 0.556, respectively; p
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- 2020
10. Comparison of early vs. delayed anakinra treatment in patients with adult onset still's disease and effect on clinical and laboratory outcomes
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Antonio Vitale, Giulio Cavalli, Piero Ruscitti, Jurgen Sota, Serena Colafrancesco, Roberta Priori, Guido Valesini, Lorenza Maria Argolini, Elena Baldissera, Elena Bartoloni, Daniele Cammelli, Giovanni Canestrari, Elena Cavallaro, Maria Grazia Massaro, Paola Cipriani, Ginevra De Marchi, Salvatore De Vita, Giacomo Emmi, Micol Frassi, Roberto Gerli, Elisa Gremese, Florenzo Iannone, Marco Fornaro, Anna Paladini, Giuseppe Lopalco, Raffaele Manna, Alessandro Mathieu, Carlomaurizio Montecucco, Marta Mosca, Ilaria Piazza, Matteo Piga, Irene Pontikaki, Micol Romano, Silvia Rossi, Maurizio Rossini, Elena Silvestri, Chiara Stagnaro, Rosaria Talarico, Bruno Frediani, Angela Tincani, Ombretta Viapiana, Gianfranco Vitiello, Paola Galozzi, Paolo Sfriso, Carla Gaggiano, Salvatore Grosso, Donato Rigante, Lorenzo Dagna, Roberto Giacomelli, Luca Cantarini, Vitale, A., Cavalli, G., Ruscitti, P., Sota, J., Colafrancesco, S., Priori, R., Valesini, G., Argolini, L. M., Baldissera, E., Bartoloni, E., Cammelli, D., Canestrari, G., Cavallaro, E., Massaro, M. G., Cipriani, P., De Marchi, G., De Vita, S., Emmi, G., Frassi, M., Gerli, R., Gremese, E., Iannone, F., Fornaro, M., Paladini, A., Lopalco, G., Manna, R., Mathieu, A., Montecucco, C., Mosca, M., Piazza, I., Piga, M., Pontikaki, I., Romano, M., Rossi, S., Rossini, M., Silvestri, E., Stagnaro, C., Talarico, R., Frediani, B., Tincani, A., Viapiana, O., Vitiello, G., Galozzi, P., Sfriso, P., Gaggiano, C., Grosso, S., Rigante, D., Dagna, L., Giacomelli, R., and Cantarini, L.
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0301 basic medicine ,myalgia ,medicine.medical_specialty ,Settore MED/16 - REUMATOLOGIA ,adult onset Still's disease ,anakinra ,autoinflammatory diseases ,innovative biotechnologies ,interleukin-1 ,personalized medicine ,systemic onset juvenile idiopathic arthritis ,treat to target ,Etanercept ,03 medical and health sciences ,0302 clinical medicine ,systemic onset juvenile idiopathic arthriti ,autoinflammatory disease ,Internal medicine ,Still's disease ,medicine ,Original Research ,030203 arthritis & rheumatology ,Anakinra ,lcsh:R5-920 ,innovative biotechnologie ,medicine.diagnostic_test ,biology ,business.industry ,C-reactive protein ,Hydroxychloroquine ,General Medicine ,medicine.disease ,Systemic-onset juvenile idiopathic arthritis ,Infliximab ,030104 developmental biology ,Erythrocyte sedimentation rate ,biology.protein ,Medicine ,medicine.symptom ,business ,lcsh:Medicine (General) ,medicine.drug - Abstract
Background: Aim of this study was to search for any difference in the outcome of patients with adult onset Still's disease (AOSD) treated with anakinra (ANK) in relation with the interval between disease onset and the start of anti-interleukin(IL)-1 treatment and according with the different lines of ANK treatment. Patients and Methods: One hundred and forty-one AOSD patients treated with ANK have been retrospectively assessed. Statistically significant differences (p < 0.05) were analyzed in the frequency of ANK effectiveness, primary or secondary inefficacy to ANK and rate of resolution of clinical and laboratory AOSD manifestations after 3, 6, and 12 months since ANK treatment according with different lines of treatment and different times between AOSD onset and start of ANK. Results: No significant differences were identified in the ANK effectiveness and frequency of primary or secondary inefficacy for patients starting ANK within 6 months (p = 0.19, p = 0.14, and p = 0.81, respectively) or 12 months (p = 0.37, p = 0.23, and p = 0.81, respectively) since AOSD onset compared with patients starting ANK thereafter; no significant differences were identified in ANK effectiveness and primary or secondary inefficacy according with different lines of ANK treatment (p = 0.06, p = 0.19, and p = 0.13, respectively). Patients starting ANK within 6 and 12 months since AOSD onset showed a significantly quicker decrease of erythrocyte sedimentation rate and C-reactive protein than observed among patients undergoing ANK treatment after 6 and 12 months. The number of swollen joints at the 3 month follow-up visit was significantly lower among patients undergoing ANK within 6 months since AOSD onset (p = 0.01), while no significance was identified at the 6 and 12 month assessments (p = 0.23 and p = 0.45, respectively). At the 3 and 6 month visits, the number of swollen joints was significantly higher among patients previously treated with conventional and biological disease modifying anti-rheumatic drugs (DMARDs) compared with those formerly treated only with conventional DMARDs (p < 0.017). Conclusions: Clinical and therapeutic outcomes are substantially independent of how early ANK treatment is started in AOSD patients. However, a faster ANK effectiveness in controlling systemic inflammation and resolving articular manifestations may be observed in patients benefiting from IL-1 inhibition as soon as after disease onset.
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- 2020
11. FRI0159 EROSIVE ARTHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS: APPLICATION OF CLUSTER ANALYSIS
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Carlo Perricone, Giulio Olivieri, Fulvia Ceccarelli, Cristiano Alessandri, Guido Valesini, Enrica Cipriano, Tania Colasanti, Fabrizio Conti, F. Natalucci, Francesca Romana Spinelli, and Carmelo Pirone
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Past medical history ,Univariate analysis ,medicine.medical_specialty ,business.industry ,Immunology ,Autoantibody ,Arthritis ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Serology ,Rheumatology ,Internal medicine ,Cohort ,Arthropathy ,medicine ,Immunology and Allergy ,Rheumatoid factor ,business - Abstract
Background:Systemic Lupus Erythematosus (SLE) related arthritis has been traditionally defined non-erosive and then considered a minor manifestation. Thanks to the application of more sensitive imaging techniques, such as ultrasonography (US), erosive damage has been identified in up to 40% of SLE patients with joint involvement, suggesting the need for more appropriate treatment (1). Antibodies directed against citrullinated and carbamilated proteins (ACPA and anti-CarP, respectively) have been associated with erosive damage and then proposed as biomarkers for this more aggressive phenotype (2).Objectives:Here, we evaluated a large SLE cohort with joint involvement by using cluster analysis, in order to identify the disease phenotype associated with erosive arthritis.Methods:For this analysis, we enrolled consecutive SLE patients (ACR 1997 criteria) with a clinical history of joint involvement (arthritis/arthralgia). Clinical and laboratory data were collected in a standardized computerized electronically filled form, including demographics, past medical history with the date of diagnosis, co-morbidities, previous and concomitant treatments, serological status. The presence of rheumatoid factor (RF), ACPA and anti-CarP was investigated by ELISA test. Erosive damage was assessed by ultrasonography at level of metacarpophalangeal, proximal interphalangeal and metatarsophalangeal joints (MyLab Eight Exp, Esaote, Florence, Italy). Data have been analysed by hierarchic cluster analysis (SPSS program, IBM).Results:We enrolled 203 patients [M/F 12/191, median age 46.0 years (IQR 18); median disease duration 120.0 months (IQR 108)]. Erosive damage was identified in 53 patients (26.1%), all of them referring at least one episode of arthritis during disease course. Moving on autoantibodies status, RF was positive in 29.5%, anti-CarP in 28.5% and ACPA in 11.2%. The univariate analysis demonstrated a significant association between US-detected erosive damage and anti-CarP (p=0.01), ACPA (p=0.03), and renal manifestations (p=0.03). In Figure 1 we reported the dendrogram obtained from cluster analysis, allowing the identification of four cluster. Positivity for ACPA, anti-CarP, erosive damage, Jaccoud’s arthropathy and renal manifestations were allocated in the same cluster. Interestingly, RF resulted allocated in a different cluster, including ENA, anti-SSA and anti-SSB antibodies.Conclusion:The application of cluster analysis allowed the identification of a specific SLE phenotype, characterized by erosive damage, renal manifestations and positivity for anti-CarP and ACPA. We could speculate about the presence of a shared pathogenic mechanism, involving NETosis, contributing to nephritis and erosive arthritis.References:[1]Ceccarelli F et al. Semin Arthritis Rheum 2017[2]Ceccarelli F et al. Arthritis Res Ther 2018Disclosure of Interests:Fulvia Ceccarelli: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, enrica cipriano: None declared, Carmelo Pirone: None declared, Giulio Olivieri: None declared, Tania Colasanti: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
12. Polymyalgia rheumatica and diverticular disease: just two distinct age-related disorders or more? Results from a case-control study
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Fulvia Ceccarelli, Guido Valesini, Francesca Romana Spinelli, Elena Pacella, Gaetana Maria Grazia Stricchiola, Chiara Castellani, Paola Sessa, Maria Chiara Gerardi, Iolanda Maria Rutigliano, Giuseppe La Torre, Antonio Sili Scavalli, Manuela Di Franco, Rossana Scrivo, Cristiano Alessandri, Daniele Mipatrini, Valeria Riccieri, Roberta Priori, Alessio Altobelli, and Fabrizio Conti
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Male ,musculoskeletal diseases ,medicine.medical_specialty ,Exacerbation ,diverticular disease ,education ,diverticulosis ,Comorbidity ,polymyalgia rheumatica ,Coronary artery disease ,Polymyalgia rheumatica ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Risk Factors ,environmental factors ,Internal medicine ,infectious agents ,Humans ,Medicine ,Outpatient clinic ,Risk factor ,Aged ,Diverticular Diseases ,gut microbiota ,030203 arthritis & rheumatology ,business.industry ,Case-control study ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,Logistic Models ,Case-Control Studies ,Diverticular disease ,Female ,030211 gastroenterology & hepatology ,business - Abstract
In a previous report of two married cohabiting couples affected by polymyalgia rheumatica (PMR), we noticed that the wife of one couple and both members of the other couple suffered from symptomatic diverticular disease (DD), whose diagnosis was made before the onset of PMR. We investigated whether DD might be a risk factor for the development of PMR. We conducted a case-control study informed on a database containing the prospectively collected medical records of consecutive PMR patients. Among comorbidities, attention was focused on symptomatic DD, provided that the diagnosis had been made by colonoscopy and/or computed tomography scan. As controls, we identified one control per case at random among those matched by age and sex attending the ophthalmic and orthopedic outpatient clinics, as long as a PMR diagnosis had been excluded. A logistic regression model was used, following a multiplicative model, and results were presented as odds ratio (OR) and 95% confidence intervals (95% CI). The most frequent comorbidities in the two groups of patients (121 cases and 121 controls) were chronic coronary artery disease, atrial fibrillation, diabetes mellitus, hypertension, DD, hypercholesterolemia, osteoporosis, chronic obstructive pulmonary disease, gastroesophageal reflux disease, and cholelithiasis. The association between PMR and DD (OR = 4.06; 95% CI: 1.76-9.35) was by far stronger than that found comparing PMR with the other comorbidities. The chronic bowel inflammation induced by dysbiosis in patients with symptomatic DD could be a critical immunopathological mechanism supporting the development or exacerbation of PMR in susceptible individuals.
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- 2018
13. Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials
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Euthalia Roussou, Caroline Gordon, Elena Rezus, Guido Valesini, ERIC HACHULLA, Tatiana Reitblat, Dana Tegzova, Vikas Agarwal, David McLain, Carle Paul, Rodriguez Heredia Jose Manuel, Anastas Batalov, Stephen Adelstein, Juan Gomez-Reino, Maria Majdan, Gerard Espinosa, Kenneth Kalunian, Russell Griffin, Andrea Doria, Lajos Kemény, Majed Khraishi, José María Pego-Reigosa, Antonio Fernandez-Nebro, Mykola Stanislavchuk, Pavel Horák, Vineeta Shobha, Falk Hiepe, and Janet Pope
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0301 basic medicine ,medicine.medical_specialty ,Anti-nuclear antibody ,Immunology ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Randomized controlled trial ,law ,Internal medicine ,Clinical endpoint ,Immunology and Allergy ,Medicine ,030203 arthritis & rheumatology ,Lupus erythematosus ,Systemic lupus erythematosus ,business.industry ,medicine.disease ,Clinical trial ,030104 developmental biology ,Physical therapy ,business ,Epratuzumab ,medicine.drug - Abstract
Author(s): Clowse, Megan EB; Wallace, Daniel J; Furie, Richard A; Petri, Michelle A; Pike, Marilyn C; Leszczynski, Piotr; Neuwelt, C Michael; Hobbs, Kathryn; Keiserman, Mauro; Duca, Liliana; Kalunian, Kenneth C; Galateanu, Catrinel; Bongardt, Sabine; Stach, Christian; Beaudot, Carolyn; Kilgallen, Brian; Gordon, Caroline; EMBODY Investigator Group | Abstract: ObjectiveEpratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE).MethodsPatients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders.ResultsIn the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified.ConclusionIn patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group.
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- 2017
14. FRI0350 FACTORS ASSOCIATED WITH PERIPHERAL EROSIVE RADIOGRAPHIC DISEASE IN A CONSECUTIVE SERIES OF 794 PSA PATIENTS
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Fabio Massimo Perrotta, L. Rotunno, M. Lofrano, Pierluigi Macchioni, Mariagrazia Lorenzin, Antonio Marchesoni, Carlo Salvarani, Guido Valesini, Giuseppe Paolazzi, Mariagrazia Catanoso, Alberto Cauli, Roberto Bortolotti, Salvatore D'Angelo, G. Mathieu, and Roberta Ramonda
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medicine.medical_specialty ,Univariate analysis ,business.industry ,Immunology ,Feet examination ,Mean age ,Odds ratio ,Disease ,medicine.disease ,Imaging data ,Tertiary care ,General Biochemistry, Genetics and Molecular Biology ,Psoriatic arthritis ,Rheumatology ,Internal medicine ,medicine ,Immunology and Allergy ,business - Abstract
Background:Few studies have examined the correlation between clinical demographic and laboratory parameters with peripherical radiological erosive disease in PsA pts.Objectives:To examine the association between clinical, demographical and laboratory data and the presence of radiographic erosions (RE) in the peripheral joints of psoriatic arthritis (PsA) pts.Methods:A cross-sectional study was conducted in consecutive patients with PsA afferring 7 rheumatological italian tertiary care centers. Demographical, clinical, laboratory and imaging data were collected according to a standardized protocol. A patient was considered as affected by erosive disease (ED) if at least one joint presented radiographic erosions at hand and/or feet rx examination. Patients with ED at early rx examination (before 5 y from disease diagnosis) were considered as early ED (EED) pts and pts without ED at 6 y or more rx examination from disease diagnosis were considered as not EED (NEED).The association between the presence of joint erosions and demographical, clinical and laboratory data was assessed using logistic regression analysis. The results were expressed in terms odds ratios (OR), and 95% confidence intervals (CI).Results:Rx hand and feet examination were available for analysis in 492/794 (39.9 % females, mean age 53.3 ± 13.2 y, mean PsA duration 16.9 ± 16.8 y, ED 171 pts). 48 pts had EED and 133 pts had NEED. At univariate analyses factors significantly associated with EED (p < 0.20) were PsA duration (OR=0.979,95%CI 0.953-1.006, p = 0.119), diagnostic delay (OR=1.077, 95%CI 1.018-1.138, p = 0.009), history of peripheral enthesitis (OR=2.308,95%CI 0.904-5.888, p= 0.080), hypertrigliceridemia (OR=2.756,95%CI 0.997-7.618, p = 0.0.051), hypercholesterolemia (OR=1.687, 95%CI 0.777-3.661, p = 0.186), hyperuricemia (OR=0.450, 95%CI 0.174-1.166, p = 0.10), use of biological agents (OR=1.712, 95%CI 0.873-3.355, p=0.118). Factors significantly associated with EED at multivariate regression analyses were diagnostic delay (OR = 1.11, 95% CI: 1.01, 1.22), history of enthesitis (OR = 3.15, 95% CI: 1.23, 8.22), use of therapy with biological agents (OR = 3.60, 95% CI: 1.31, 9.85) with protective effect of hyperuricemia (OR = 0.25, 95% CI: 0.07, 0.90).Conclusion:The presence of EED in a group of consecutive PsA patients is correlated to diagnostic delay and history of enthesitis. Longitudinal study may confirm these associations.Disclosure of Interests:Maria Grazia Catanoso: None declared, Pierluigi Macchioni: None declared, Antonio Marchesoni Speakers bureau: Abbvie, Pfizer, UCB, Novartis, Celgene, Eli Lilly, Salvatore D’Angelo Speakers bureau: AbbVie, Biogen, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sanofi, and UCB, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Alberto Cauli: None declared, fabio perrotta: None declared, Roberto Bortolotti: None declared, mariana lofrano: None declared, laura rotunno: None declared, maria grazia lorenzin: None declared, Guido Valesini: None declared, giovanni mathieu: None declared, Giuseppe Paolazzi: None declared, Carlo Salvarani Grant/research support from: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis, Consultant of: consulting and investigator fees from Abbvie, Pfizer, MSD, Roche, Celgene, Novartis
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- 2020
15. SAT0555 MUSCULOSKELETAL ULTRASOUND IN MONITORING RESPONSE TO JAKi IN RHEUMATOID ARTHRITIS PATIENTS: RESULTS FROM A LONGITUDINAL STUDY
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Enrica Cipriano, C. Garufi, I. Duca, M. Di Franco, Cesare Alessandri, Rossana Scrivo, S. Mancuso, Fabrizio Conti, Valeria Riccieri, F.R. Spinelli, Carlo Perricone, Fulvia Ceccarelli, Guido Valesini, and Roberta Priori
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Past medical history ,Longitudinal study ,medicine.medical_specialty ,Tofacitinib ,business.industry ,Immunology ,Context (language use) ,Musculoskeletal ultrasound ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,law.invention ,Rheumatology ,Randomized controlled trial ,law ,Rheumatoid arthritis ,Concomitant ,Internal medicine ,medicine ,Immunology and Allergy ,business - Abstract
Background:Therapeutic approach of rheumatoid arthritis (RA) patients has been enriched by the introduction of small molecules. In particular Jak inhibitors (JAKi), baricitinib and tofacitinib, demonstrated their efficacy in patients naïve or resistant to biological treatments in randomized controlled trials. Moreover, these drugs seem to be able to prevent radiographic progression. To date few data are available from the real life context. Ultrasonographic (US) assessment has became a valid imaging tool in the management of RA patients in clinical practice, allowing the evaluation of joint inflammatory status. Together with clinimetric assessment, US could provide a comprehensive assessment of drug response.Objectives:In the present study we aimed at assessing the early response to JAKi treatment by using musculoskeletal US.Methods:In this prospective longitudinal study, we collected data about all consecutive active RA patients starting treatment with JAKi. RA was diagnosed according to the 2010 ACR/EULAR criteria. At each visit, clinical and laboratory data were collected in a standardized and computerized form, including demographics, past medical history, co-morbidities, previous and concomitant treatments. According with study protocol, all patients underwent clinical and US assessment at the following time-points: baseline (T0), 4 weeks (T1) and 12 weeks (T2). Clinical evaluation included tender and swollen joint counts (0-28), patients global health assessment. C-reactive protein (CRP) levels were registered and disease activity was calculated by disease activity score (DAS) in 28 joints by using CRP (DAS28-CRP). A systematic multiplanar grey-scale and power Doppler (pD) US examination was performed by using MyLab Eight Exp Machine (Esaote, Florence, Italy) at level of 22 joints (bilateral I-V metacarpophalangeal, I-V proximal interphalangeal, wrist). According with OMERACT definitions (1) we assessed the presence of synovial effusion, hypertrophy and pD, that were scored according to a semi-quantitative scale (0-3). A total US inflammatory score (0-198) was obtained by their sum.Results:We enrolled 91 patients [F/M 77/14; median age 60.0 years (IQR 15.5); median disease duration 144 months (IQR 126)]. Of these patients, 54 (59.3%) were treated by baricitinib and the remaining 37 by tofacitinib. At baseline we found a median US inflammatory score of 20 (IQR 18.7) and a median DAS28-CRP of 5.0 (IQR 1.56). US assessment demonstrated significant reduction in the median values of inflammatory score already at T1 [median 13 (IQR 14.7), pConclusion:In the present study, specifically designed to evaluate the US-detected efficacy of JAKi in RA patients, we demonstrated in a real life setting a significant, early and sustained improvement of inflammatory joint status.References:[1]Wakefield et al, J Rheumatol 2005Disclosure of Interests:enrica cipriano: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Cristina Garufi: None declared, Ilaria Duca: None declared, Silvia Mancuso: None declared, cristiano alessandri Grant/research support from: Pfizer, Manuela Di Franco: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Carlo Perricone: None declared, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
16. THU0627-HPR JOINT INVOLVEMENT SIGNIFICANTLY INFLUENCES QUALITY OF LIFE OF PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS
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F.R. Spinelli, Francesca Miranda, Fabrizio Conti, Fulvia Ceccarelli, Guido Valesini, Cesare Alessandri, F. Natalucci, Enrica Cipriano, Carlo Perricone, Simona Truglia, and Giulio Olivieri
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Disease specific ,medicine.medical_specialty ,Systemic lupus erythematosus ,business.industry ,Immunology ,Arthritis ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Group B ,Rheumatology ,Quality of life ,Clinical history ,Joint involvement ,Internal medicine ,Cohort ,medicine ,Immunology and Allergy ,business - Abstract
Background:Joint involvement is one of the most common features observed in Systemic Lupus Erythematosus (SLE), potentially involving up to 90% of patients [1]. Several patients’ reported outcomes (PROs) have been employed to measure Quality of life (QoL) in SLE patients, but frequently not specifically developed for SLE patients. More recently, the LupusQoL has been validated, a disease specific questionnaire[2,3].Objectives:We focused at assessing the relationship between musculoskeletal manifestations and QoL in a large SLE cohort, by using the LupusQoL.Methods:SLE patients with a clinical history of joint involvement (arthralgia/arthritis – group A) were enrolled in the present study. SLE diagnosis was performed according to the revised 1997 ACR criteria. As a control group, we enrolled SLE patients without history of joint involvement (group B).Disease activity was assessed by the SLE Disease Activity Index-2000 (SLEDAI-2k). The activity of joint involvement was assessed by using the disease activity score on 28 joints (DAS28ESR). The LupusQoL was administered to the enrolled patients (Group A and Group B). It consists of 34 items referring to eight domains: physical health (PH), pain (P), planning (PL), intimate relationships (IR), burden to others (BO), emotional health (EH), body image (BI) and fatigue (F).Results:Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], while group B included 58 patients [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)]. Group A showed a significantly lower disease duration and mean age in comparison with group B (P< 0.001 for both comparisons). As represented in figure 1, group A showed significantly lower values in all LupusQoL domains except for “burden to others” domain. Moreover, we observed an inverse correlation between DAS28ESRand all the LupusQoL domains in group A patients [PH (r=-0.5, P>0.0001), P (r=-0.5, PFigure 1.Conclusion:In the present study, by using a disease specific PRO, we found a poorer QoL in SLE patients with joint involvement in comparison with those without this manifestation. Moreover,DAS28ESRsignificantly correlated with all LupusQol domains, differently from SLEDAI-2k, suggesting the need to evaluate joint involvement with a specific activity index.References:[1]Cervera R et al. Medicine 1993[2]McElhone K. et al. Arthritis Rheum 2007.[3]Conti F et al. Lupus 2014Group (A)Group (B)pPH80,38 ± 21,4362,88 ± 23.28< 0.0001P82,36 ± 25.0862,30± 26.02< 0.0001PL83,04 ± 27.8270,58± 29.450.001IR84,49± 25.9965,36± 36.330.0005BO69,58 ± 28.4663,45± 28.950.129EH71,98 ± 24.6964,69± 23.050.0169F73,69 ± 24.2959,78±26.060.0004B78,14 ± 24.6156,28±30.14Disclosure of Interests:Francesco Natalucci: None declared, Fulvia Ceccarelli: None declared, enrica cipriano: None declared, Giulio Olivieri: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, Simona Truglia: None declared, Francesca Miranda: None declared, cristiano alessandri Grant/research support from: Pfizer, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Guido Valesini: None declared
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- 2020
17. AB0085 MODULATION OF CIRCULATING SKELETAL STAMINAL CELLS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOFACITINIB
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Marta Vomero, C. Garufi, Fabrizio Conti, Cristiana Barbati, Tania Colasanti, F.R. Spinelli, Cesare Alessandri, Fulvia Ceccarelli, Guido Valesini, and I. Duca
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medicine.medical_specialty ,Tofacitinib ,biology ,business.industry ,Immunology ,medicine.disease ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Peripheral blood ,Rheumatology ,Rheumatoid arthritis ,Internal medicine ,Bone cell ,medicine ,biology.protein ,Immunology and Allergy ,Antibody ,Stem cell ,business ,PDPN ,After treatment - Abstract
Background:Rheumatoid arthritis (AR) is an autoimmune systemic inflammatory disease characterized by chronic synovial inflammation resulting in bone damage and erosions, with consequently functional disability. Currently, attempts for regenerative therapies for osteo-cartilage pathologies have proved unsuccessful. Recently, a “pool” of skeletal stem cells (hSSCs: human skeletal stem cells) able to generating bone cells, has been identified in human bone (1).Objectives:In light of these observations, we aim at characterizing skeletal stem cells in peripheral blood from RA patients candidate to Tofacitinib treatment.Methods:In this pilot study 4 RA patients [4F; mean age 65 years; mean disease duration 19 years] candidate to Tofacitinib treatment and 4 healthy donors (HD), matched by gender and age, were enrolled. Blood samples were collected from each subject of the study, at baseline (T0) and for RA patients, after 1 month of Tofacitinib (T1), to evaluatinghSSC(CD45-, CD146-, CD73+, PDPN+, CD164+) by flow cytometry. For this purpose, we performed on whole blood a negative magnetic selection for CD45 cells. Then, the eluate was labeled with antibodies anti CD146-PE, anti CD73-APC, anti CD164 - FITC and anti-Podoplanin (PDPN) PerCP/Cyanine5.5. The acquisition was performed using a FACS Calibur, which included 100,000 events per sample (Figure 1).Results:ThehSSCspercentage was significantly lower in RA patients than in HD (p = 0.0286). At T1, after treatment with Tofacitinib, meanhSSCspercentage significantly increased from 1.8% to 4.2 % (p = 0.016 vs RA T0) (Figure 2A). Correlation analysis showed a significant indirect relation between the percentage ofhSSCand disease activity measured by DAS28ESR, SDAI and CDAI (Figure 2B).Conclusion:The results of this study demonstrate, for the first time, circulating skeletal stem cells and their reduced expression in active RA patients. Tofacitinib treatment leads to a significant increase inhSSCspercentage. This evidence opens up new perspectives on bone repair mechanisms and on deepening of current therapeutic strategies.References:[1]Chan CKF, Gulati GS, Sinha R, Tompkins JV, Lopez M, Carter AC, Ransom RC, Reinisch A, Wearda T, Murphy M, Brewer RE, Koepke LS, Marecic O, Manjunath A, Seo EY, Leavitt T, Lu WJ, Nguyen A, Conley SD, Salhotra A, Ambrosi TH, Borrelli MR, Siebel T, Chan K, Schallmoser K, Seita J, Sahoo D, Goodnough H, Bishop J, Gardner M, Majeti R, Wan DC, Goodman S, Weissman IL, Chang HY, Longaker MT.Identification of the Human Skeletal Stem Cell.Cell. 2018 Sep 20;175(1):43-56.e21. doi: 10.1016/j.cell.2018.07.029.Acknowledgments:noneDisclosure of Interests:cristiana barbati: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristina garufi: None declared, Ilaria Duca: None declared, fulvia ceccarelli: None declared, Tania Colasanti: None declared, Marta Vomero: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
18. AB0220 ALPHA- SMOOTH MUSCLE ACTIN EXPRESSION ON ENDOTHELIAL PROGENITORS CELLS OF SYSTEMIC SCLEROSIS PATIENTS: POSSIBLE ROLE IN THE ENDOTHELIAL-TO-MESENCHIMAL TRANSITION PROCESS
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Cristiano Alessandri, Katia Stefanantoni, Carlotta Angelelli, Cristiana Barbati, Valeria Riccieri, Greta Pellegrino, and Guido Valesini
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Lymphocyte ,CD34 ,Alpha (ethology) ,Arthritis ,medicine.disease ,Flow cytometry ,Pathogenesis ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,cardiovascular system ,medicine ,Progenitor cell ,business ,circulatory and respiratory physiology ,Iloprost ,medicine.drug - Abstract
Background Endothelial-to-mesenchymal transition (EndoMT), a newly recognized type of cellular transdifferentiation, seems to be involved in Systemic Sclerosis (SSc) pathogenesis. In this process endothelial cells lose their specific markers, and acquire a mesenchymal phenotype, thus expressing cell products such as alpha smooth muscle actin (α-SMA) (1,2). Circulating endothelial progenitors cells (EPCs) derive from bone marrow stem cells and contribute to de novo vessels formation. Several studies, although with conflicting results, have shown that EPCs in the peripheral blood of patients with SSc are impaired in their number and function (3). Objectives to assess the expression of α-SMA, possibly associated with a pro-mesenchymal switch (EndoMT) of the circulating Early (CD34+KDR+CD 133+) and Late (CD34+KDR+) EPCs in the peripheral blood of SSc patients and of patients with Very Early Diagnosis of SSc (VEDOSS) compared with healthy controls (HC) using flow cytometry. Methods we enrolled 11 patients (7 SSc and 4 VEDOSS), classified according to the classification criteria for SSc (4) and for VEDOSS not fulfilling SSc criteria (5), and 10 HC. Phenotypic characterization was performed as previously described by Vasa et al. using a FACS Calibur (BD Immunocytometry Systems). EPCs number was expressed as a percentage of cells within the lymphocyte gate. Results we found a significantly higher percentage of α-SMA positive Early EPCs (CD34+KDR+CD 133+αSMA+) in all patients respect to HC (0,06% ±0,03 vs 0,03% ± 0,01; p=0,0149) particularly in VEDOSS patients (0,07%±0,01 vs 0,03±0,01 p=0,008). Moreover, in VEDOSS patients, also the percentage of Early EPCs (CD34+KDR+CD 133+), Late EPCs (CD34+KDR+)and α-SMA positive Late EPCs (CD34+KDR+αSMA+) were significantly higher than in HC (0,05%±0,01 vs 0,03%±0,01 p=0,05; 0,07%±0,01 vs 0,04%±002 p=0,04; 0,06%±0,01 vs 0,04%±0,02 p=0,05). Besides Early EPCs and α-SMA positive Early EPCs percentages seem to be significantly reduced in patients taking iloprost (p=0,05 and p=0,01 respectively), calcium channel blockers (CCB) (p=0,05 and p=0,03) and DMARDs (p=0,017 and p=0,013). Conclusion EndoMT seems to be involved in the pathogenesis of SSc and circulating EPCs seem to be impaired in number and function in SSc patients. In our study we found higher levels of EPCs, in particular α-SMA positive Early EPCs in both groups of patients (SSc and VEDOSS) respect to HC. Thus we can hypothesize a predominant pro-mesenchymal phenotype of this kind of EPCs. This could be considered the expression of the involvement of EPCs in EndoMT process and could better explain the controversial role of EPCs in SSc pathogenesis. Very interesting is the finding of a lower percentage of Early EPCs, and in particular of α-SMA positive Early EPCs, in those patients taking iloprost, CCB and DMARDs, suggesting a potential effect of these drugs on this subgroup of EPCs. References [1] Corallo C, et al. Arthritis Res Ther2016; [2] Manetti M, et al. Ann Rheum Dis2017; [3] Del Papa N, et al. Front. Immunol2018; [4] Van den Hoogen F, et al. Ann Rheum Dis2013; [5] Avouac J, et al. Ann Rheum Dis2011. Disclosure of Interests Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, cristiana barbati: None declared, Carlotta Angelelli: None declared, Greta Pellegrino: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared
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- 2019
19. FRI0247 PROGNOSTIC ROLE OF TUBULO-INTERSTITIAL INFILTRATE IN PATIENTS AFFECTED BY LUPUS NEPHRITIS
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C. Garufi, Simona Truglia, F. Morello, Fulvia Ceccarelli, Cristiano Alessandri, V. A. Pacucci, Guido Valesini, Konsantinos Giannakakis, Francesca Romana Spinelli, and Fabrizio Conti
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Nephrology ,education.field_of_study ,medicine.medical_specialty ,Kidney ,Systemic lupus erythematosus ,medicine.diagnostic_test ,business.industry ,Population ,Lupus nephritis ,medicine.disease ,Gastroenterology ,medicine.anatomical_structure ,Renal pathology ,Internal medicine ,Biopsy ,medicine ,Renal biopsy ,education ,business - Abstract
Background: Lupus nephritis (LN) occurs up to 50% of patients affected by Systemic Lupus Erythematosus (SLE) representing one of the major causes of morbidity and mortality in lupus population (1). Kidney biopsy is a fundamental tool for the diagnosis and management of lupus nephritis. The presence of pathological changes such as inflammatory infiltrate in glomeruli and/or in tubulo-interstitium are relevant in terms of prognosis and response to therapy (2). Objectives: The aim of the study was to correlate the clinical and laboratory findings and the response to therapy with presence of glomerular and/or interstitial infiltrate in kidney section of patients with a biopsy-proven LN. Methods: Kidney sections of patients with SLE undergoing a renal biopsy for diagnostically purpose were studied; samples were classified according to the 2004 International Society of Nephrology/Renal Pathology Society classification criteria (3). Clinical, laboratory and histological data were collected in a standardized, computerized and electronically filled form, including demographics, past medical history, autoantibody profile, previous and concomitant treatments. We assessed the disease activity by using SLEDAI-2K and remission in response to therapy was defined as the absence of renal impairment and as a score 0 of renal SLEDAI (proteinuria Results: We evaluated 53 kidney samples from patients with LN (F:M = 51:2, mean age at biopsy 35±7.7 years; mean disease duration at date of biopsy 8±8.3 years). Class IV (46%) was the most common class followed by class III (29%), class II (13%), class V (11.5%) and class VI (0,5%). Tubulo-interstitial infiltrate was found in 33 kidney specimens, with germinal centres (GC)-like features in 13 renal samples (Figure 1). During the follow up (6±3.8 years) the tubulo-insterstitial infiltrate, either diffuse or with GC-like feature, was negatively correlated with renal remission (P=0.03). Conclusion: Assessment and management of patients with LN are greatly facilitated by information obtained by renal biopsy. In the present study we demonstrate that the presence of tubulo-interstital infiltrate is associated with a worse outcome in response to therapy. Our data highlight the importance of tubulo-interstitium damage, scarcely considered in the current classification criteria, since it represents a key point to predict long-term prognosis. References: [1] Schwartz N, et al. Curr Opin Rheumatol. (2014) [2] Giannakakis K, et al. Clinic Rev Allerg Immunol (2011) [3] Weening JJ, et al. J Am Soc Nephrol (2004) [4] Gladman DD, et al. J Rheumatol (2002) [5] Houssiau FA, et al. Arthritis Rheum (2002) [6] Hahn BH, et al. Arthritis Care & Research (2012) Disclosure of Interests: None declared
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- 2019
20. AB0422 ACHIEVEMENT OF PATIENT ACCEPTABLE SYMPTOM STATE (PASS) IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH BARICITINIB
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Cristiano Alessandri, C. Garufi, I. Duca, Francesca Romana Spinelli, Fulvia Ceccarelli, Guido Valesini, S. Mancuso, and Fabrizio Conti
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Ankylosing spondylitis ,medicine.medical_specialty ,Response to therapy ,business.industry ,Baricitinib ,Arthritis ,Disease ,medicine.disease ,law.invention ,Randomized controlled trial ,law ,Rheumatoid arthritis ,Internal medicine ,Cohort ,Medicine ,business - Abstract
Background: Baricitinib, a newly approved drug for the treatment of patients with moderate to severe rheumatoid arthritis (RA), is a selective inhibitor of Janus kinase 1 and 2. In a patient-centered care, patient-reported outcomes (PROs) are really helpful to better evaluate the disease activity and the response to therapy. Between them, Patient Acceptable Symptom State (PASS) is defined as the highest level of symptoms beyond which patients consider themselves well [1], and consists of a single question with dichotomized answer (yes or no): “Considering all the different ways your disease is affecting you, if you would stay in this state for the next months, do you consider that your current state is satisfactory?”. In randomized controlled trials baricitinib showed significant improvement of pain, fatigue, tiredness and assessment of disease [2]. Objectives: The aim of the present study was to investigate the effect of baricitinib on PASS one month from the beginning of therapy. Further aim was to quantify the time patients needed to reach an acceptable state of health and determine the clinical variables associated with PASS. Methods: Patients affected by RA according to 2010 ACR criteria, starting treatment with baricitinib as clinically indicated, were consecutively enrolled; PASS was determined after 1 month of treatment (T1); days to achieve PASS were estimated at T1; activity indices were calculated after 1 month of therapy and correlated with PASS. Results: Thirty-four RA patients were enrolled (age median-IQR 58-16 years; disease duration median-IQR 144-138 months; DAS-28 median-IQR 5.09-1.92). After 1 month of therapy, 30 of 34 patients achieved PASS, of which 73% in the first 2 weeks of treatment (days to achieve PASS median-IQR 12-22) (figure). At T1, patients achieving PASS, compared to those who did not, reported less pain (median VAS 30/100 vs 72/100, p= 0.025), a better global assessment of disease (median 40/100 vs 72/100, p=0.023), lower CDAI (median 12 vs 31, p= 0.048), SDAI (median 12.8 vs 33.95, p=0.011) and DAS-28 (median 3.67 vs 5.54, p= 0.082). 10 out of 30 PASS positive patients (33%) achieved a DAS-28 low-disease activity or remission at T1 vs 0% of the PASS negative cohort (p= 0.169). Age, disease duration and number of previous bDMARDs did not significantly differ between the two subgroups. Conclusion: Baricitinib was able to induce an acceptable state of health in about 90% of patients after the first month of therapy. The prompt effect of baricitinib on pain and fatigue could partially explain the rapid achievement of PASS, as shown by the decrease of VAS and improvement of the global assessment of disease. References [1] Maksymowych WP, et al. Evaluation and validation of the patient acceptable symptom state (PASS) in patients with ankylosing spondylitis. Arthritis Rheum 2007 [2] Schiff, et al. Patient-reported outcomes of baricitinib in patients with rheumatoid arthritis and no or limited prior disease-modifying antirheumatic drug treatment. Arthritis Res Ther. 2017 Disclosure of Interests: None declared
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- 2019
21. FRI0364 T REGULATORY CELLS AS BIOMARKER OF DISEASE ACTIVITY AND RESPONSE IN PSORIATIC ARTHRITIS PATIENTS: RESULTS FROM APREMILAST-TREATED COHORT
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Fulvia Ceccarelli, Guido Valesini, Fabrizio Conti, Carlo Perricone, Francesca Romana Spinelli, Rossana Scrivo, Ilenia Pacella, Arianna Forniti, Simona Truglia, Enrica Cipriano, Ramona Lucchetti, Silvia Piconese, Vincenzo Barnaba, Francesca Miranda, and Cristiano Alessandri
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030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,business.industry ,FOXP3 ,medicine.disease ,Gastroenterology ,Peripheral blood mononuclear cell ,Disease activity ,03 medical and health sciences ,Power doppler ,Psoriatic arthritis ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Cohort ,medicine ,Biomarker (medicine) ,Apremilast ,business ,medicine.drug - Abstract
Background The PDE4-inhibitor apremilast has been recently introduced in the treatment of Psoriatic Arthritis (PsA). It acts by down-regulating intracellular inflammatory mediators synthesis by elevating cAMP levels. Tregs, a subset of FOXP3+ CD4 T cells, play a key role in preventing immune responses and could exert their suppressive function via cAMP (1). Reduced frequencies of circulating Tregs have been observed in inflammatory disorders, nonetheless very few data are available on PsA patients. Objectives We evaluated peripheral Tregs in a cohort of PsA patients treated by apremilast. Methods Seventeen PsA patients (M/F 3/14; median age 56.0 years, IQR 20.0; median disease duration 15.0 years, IQR 11.0) with polyarticular subset treated by apremilast, were evaluated at baseline (T0) and after 6 (T1) and 12 weeks (T1). Clinimetric evaluation included DAS28, DAPSA, CDAI, and SDAI. Moreover, US assessment was performed at wrists, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints: synovial effusion/hypertrophy and power Doppler were scored by a semi-quantitative scale (0-3), obtaining a total score (0-198). Treg frequency was assessed in peripheral blood mononuclear cells by flow cytometry, as the percentage of CD127low FOXP3+ in live CD4+ T cells (%Treg). Results At baseline we identified a median%Tregs of 4.6 (IQR 1.1), inversely correlating with DAS28 (r=-0.5, p=0.02), DAPSA (r=-0.7, p=0.003), CDAI (r=-0.6, p=0.01), SDAI (r=-0.6, p=0.003 and US inflammatory score (r=-0.6, p=0.01) (Figure 1). Treatment with apremilast was able to induce a significant improvement in all activity indices at T1 (DAS28, P=0.009; DAPSA, P=0.01; CDAI, P=0.005; SDAI, P=0.006; US score, P Conclusion The results of our study demonstrate that%Treg is a marker of disease activity in PsA patients. Moreover, the baseline value of Tregs could predict the response to apremilast after 12 weeks of treatment. Reference: [1] Chavele KMet al, FEBS Lett2011. Disclosure of Interests Fulvia Ceccarelli: None declared, Ilenia Pacella: None declared, Ramona Lucchetti: None declared, Arianna Forniti: None declared, francesca spinelli: None declared, enrica cipriano: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, Rossana Scrivo: None declared, cristiano alessandri: None declared, Vincenzo Barnaba: None declared, Guido Valesini: None declared, Silvia Piconese: None declared, fabrizio conti: None declared
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- 2019
22. AB0389 BIOSIMILAR ETANERCEPT VERSUS ORIGINATOR: RESULTS FROM A LONGITUDINAL PROSPECTIVE MONOCENTRIC STUDY
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Francesca Romana Spinelli, Fulvia Ceccarelli, Guido Valesini, Carlo Perricone, Francesca Miranda, Valeria Riccieri, Cristiano Alessandri, Ramona Lucchetti, Simona Truglia, Fabrizio Conti, Rossana Scrivo, Roberta Priori, Antonio Sili Scavalli, and Manuela Di Franco
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medicine.medical_specialty ,Visual analogue scale ,business.industry ,Arthritis ,medicine.disease ,Etanercept ,Tolerability ,Concomitant ,Internal medicine ,Rheumatoid arthritis ,Cohort ,medicine ,Prospective cohort study ,business ,medicine.drug - Abstract
Background The introduction of TNF inhibitors have revolutionized the outcome of patients affected by Rheumatoid Arthritis (RA). In the last years, pharmaco-economic implications determined the introduction of biosimilar as alternative to originator biological drugs. Phase I and head-to-head phase III clinical studies demonstrated pharmacokinetic equivalence and comparability in terms of efficacy, safety, immunogenicity and tolerability. However, biosimilar drugs demonstrated some differences related to charge and glycosylation, not influencing the function and the ability to bind the soluble TNF. To date, very few data are available concerning the use of biosimilar drugs in a real-life setting. Results from DANBIO registry suggested a lower retention rate in RA patients switchers from Etanercept originator (ETA) to biosimilar (SB4) versus the historic ETA cohort and higher in comparison with historic SB4 patients (1). Objectives To compare the efficacy of ETA versus SB4 in a cohort of RA patients in a real life setting. Methods In this monocentric case-control prospective study, we consecutively enrolled RA patients starting ETA or SB4 treatment from 2015. RA diagnosis was made according with ACR/EULAR 2010 criteria (2). Data were collected and entered into a standardized, computerized, electronically filled-in form. We included patient demographics, date of diagnosis, comorbidities and previous and concomitant medications. The clinical evaluation included the count of swollen and tender joints and the patient‘s and physician’s global disease assessment based on a visual analogue scale (VAS; range, 0 to 100 mm). Disease activity was measured according to the disease activity score in 28 joints (DAS28ESR) (3). The patients were asked to fill in the Health Assessment Questionnaire (HAQ). All the patients were evaluated at the beginning of treatment (T0) and after 4 (T1) and 12 months (T2). Clinical response to treatment was evaluated by using EULAR criteria (4). Results We evaluated 35 RA patients treated with SB4 (M/F 2/33; median age 63 years, IQR 21; median disease duration 108 months, IQR 138) and 40 with ETA (M/F 5/35; median age 60.5 years, IQR 20; median disease duration 102 months, IQR 141). Biologic drug was prescribed as first-line biological treatment in 71.4% of SB4 cohort and in 80.0% of ETA. At T0 no significant differences were observed among the two groups in terms of DAS28ESR [SB4 median 4.6 (IQR 1.8), ETA 4.3 (IQR 1.9), p=ns] and HAQ [SB4: median 1 (IQR 1.05), ETA median 1 (IQR 0.85), p=ns]. In both groups we observed a significant reduction of DAS28 values at T1 (BS4 p=0.01; ETA p Conclusion The results of our study confirmed in a real-life setting the efficacy of SB4 in RA patients, as demonstrated by the significant reduction of DAS28ESR values after 4 and 12 months of treatment, similarly to ETA. Nonetheless, ETA seems to be able to induce a remission status earlier than SB4. References [1] Glintborg B, et al. Ann Rheum Dis. 2018 [2] Aletaha D, et al. Arthritis Rheum. 2010 [3] Anderson JK, et al. Arthritis Care Res. 2011 [4] van Gestel AM, et al. Arthritis Rheum. 1996 Disclosure of Interests Ramona Lucchetti: None declared, Fulvia Ceccarelli: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, Manuela Di Franco: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Antonio Sili Scavalli: None declared, francesca spinelli: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, Roberta Priori: None declared, fabrizio conti: None declared
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- 2019
23. AB0688 NEOPLASTIC RISK IN SYSTEMIC SCLEROSIS: A MONOCENTRIC STUDY
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Massimiliano Vasile, I. Sciarra, Valeria Riccieri, Natalia Di Tommaso, Elena Marafioti, Katia Stefanantoni, Guido Valesini, Nicoletta Iannace, Greta Pellegrino, and Carlotta Angelelli
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medicine.medical_specialty ,business.industry ,Thyroid ,Autoantibody ,medicine.disease ,Gastroenterology ,Scleroderma ,Precancerous condition ,medicine.anatomical_structure ,Breast cancer ,Internal medicine ,Cohort ,Medicine ,Neoplasm ,Esophagus ,business - Abstract
Background: an increased risk of malignancies (1.5-5 times) was found in Systemic Sclerosis (SSc). Well recognized risk factors are the diffuse form, advanced age and (1), more recently, the positivity for anti-RNA Polimerase III antibodies (aRNAP3) has assumed considerable importance (2). Objectives: the aim of this study was to evaluate the frequency of neoplasms and precancerous conditions, as well as the main risk factors, in our cohort of patients with SSc. Methods: we enrolled 312 consecutive patients (288/92% females and 24/8% males, mean age 62.3 years, average disease duration 108 months) afferent at our department from 2000 to 2018, with a diagnosis of SSc confirmed according to the 2013 aCR/EULAR criteria (3). All patients underwent clinical, instrumental and laboratory evaluation. In 93 patients, negative for anti-topoisomerase I antibodies (aScl70) and anti-centromere antibodies (ACA), the presence of aRNAP3 antibodies was evaluated by an ELISA method (QUANTA LiteTM RNA Pol III). Results: we found a limited form of disease in 229 patients (73.4%) and a diffuse form in 83 (26.6%). Eighty eight (28.2%) patients were positive for aScl70, 112 (35.9%) for aCA and 17 (5.4%) for aRNAP3. In the whole group, 44 (14%) patients had a positive familiar history for neoplasm while 105 (33.65%) had a history of neoplasms and/or precancerous conditions. Among these 105 cases, 44 (41.9%) were malignant, 50 (47.6%) benign and 11 (10.5%) had precancerous conditions. The most frequent neoplasms were breast carcinomas (14 cases/14.9%), thyroid (7 cases/7.4%), lung and kidney (3 cases/3.1%), melanomas (5 cases/5.3%). The most frequent precancerous condition was Barrett’s esophagus (7 cases/63.3%). Regarding the antibody profile, 5 (4.8%) patients were positive for anti-RNAP3 and only 2 (1.9%) of these patients presented a malignant neoplasm, breast cancer in both cases. In 30 cases (28.6%) these neoplastic/precancerous conditions had arisen in the close period (± 36 months) at the SSc diagnosis and only 3 of them were anti-RNAP3 positive. Among the evaluated risk factors. Only familiarity was significantly associated with the development of neoplasia (p = 0.003), confirmed at the multivariate analysis (OR 2.9, IC95% [1,5-5,7]; p=0,002). Conclusion: our study evaluated not only malignant neoplasms, but also benign neoplasms and precancerous conditions and identified familiarity as the only significant risk factor. In our cohort we did’nt find any relationship between the presence of anti-RNAP3 antibodies and the development of neoplasms, not even stratifying for the type of neoplasm. However, to better define our data, we should analyze anti-RNAP3 also in the double negative (antiScl70 and aCA) cases, in light of the recent evidence of double antibody positivity, as well as other newly investigated rare autoantibodies, associated with neoplasm in many connective tissue diseases, including SSc. References [1] Szekanecz E, et al. (2012) autoimmun Rev11, 852; [2] Shaha aAet al(2017) J Scleroderma Relat Disord. 2, 153; [3] Van den Hoogen F, et al. (2013) ann Rheum Dis72, 1747–55. Disclosure of interests: Katia Stefanantoni Consultant for: only 1 scientific advice for Italfarmaco in 2016, Natalia Di Tommaso: None declared, Nicoletta Iannace: None declared, Iliana Sciarra: None declared, Carlotta angelelli: None declared, Elena Marafioti: None declared, Greta Pellegrino: None declared, massimiliano vasile: None declared, Guido Valesini: None declared, Valeria Riccieri: None declared
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- 2019
24. SAT0180 EVALUATION OF FRAILTY IN SJÖGREN’S SYNDROME: CREATION OF A FRAILTY INDEX
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Marco Canevelli, Angelica Gattamelata, Raffaella Izzo, Roberta Priori, Guido Valesini, Serena Colafrancesco, Giuseppe Bruno, Francesca Arienzo, Antonina Minniti, Valeria Raparelli, Francesca Remiddi, and Federica Quarata
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medicine.medical_specialty ,Pediatrics ,education.field_of_study ,business.industry ,Stressor ,Population ,Cognition ,Rheumatology ,Checklist ,Test (assessment) ,Correlation ,Internal medicine ,Mann–Whitney U test ,Medicine ,business ,education - Abstract
Background: Frailty is a condition characterized by the reduction of the individual’s homeostatic reserves, leading to an increased vulnerability to stressors and an increased risk of unfavourable events. The aging of the population and the consequent need to implement new paradigms of care and assistance, have given this tool a growing interest in many medical disciplines1. In rheumatology, however, the interest is still limited2. The Frailty Index (FI), developed on an arithmetical model of deficit accumulation, is an accurate tool for assessing frailty, providing an estimate of the biological aging. Objectives: Creation of a FI to be used in clinical practice in patients with Sjogren’s syndrome (SS) and evaluation of the correlations with patient‘s age, duration of illness, activity and disease damage at baseline and in the following 5 years. Methods: The FI is composed by a checklist of non-predefined variables (deficits) constituted by symptoms, signs, diseases, disabilities, and laboratory findings. The deficits must meet these criteria: age-related; associated with negative outcomes; multidimensional (referring to different domains of the health status); present in at least 1%, but not more than 80% of the sample. To each variable is assigned the value of 0 (= no deficit) or 1 (= deficit). The FI is the ratio between deficits presented by the individual and the total number of deficits considered, thus providing a measure of frailty ranging between 0 (no frailty) and 1 (maximum of frailty)3. A FI was developed for patients with SS consisting of 43 items (17 comorbidities, 14 signs and symptoms, 5 disabilities and 7 laboratory findings). Statistical analysis was performed with Spearman’s test for correlation assessment, the Mann Whitney test for comparing non-parametric variables was used. Results: FI was administered to a first small group of 30 female consecutive patients recruited as outpatients at the clinic dedicated to SS. The average age was 57.2 yrs, mean age at diagnosis 52.7 yrs and average disease duration 4.7 yrs. At the time of completing the FI, the average disease activity (ESSDAI) was 3.4, the mean value of the damage (SjSDDI) 1.6 and the average score of FI equal to 0.21. A statistically significant correlation between FI and age has been reported (p = 0.017). No significant correlations between frailty and duration, activity and disease damage have been highlighted at the moment. Conclusion: For the first time a FI was developed for patients with SS consisting of 43 items. The data shows a relationship between age andFI. The correlation is statistically significant, similarly to what is reported in the literature for other conditions. This confirms that FI is indeed an objective marker of aging and even though the sample population is young (average age = 57.2 years), FI maintains its main properties. This tool can be used to assess the health status of patients, making it possible to identify those at greater risk of trajectories or unfavourable outcomes. It is currently being administered the FI to patients with SS whose clinical course will be evaluated in the next 5 years (complications, mortality, hospitalization, institutionalization and disability). References [1] Canevelli M, et al, Promoting the Assessment of Frailty in the Clinical Approach to Cognitive Disorders, Front. Aging Neurosc 2017 [2] Rockwood MR, et al, FI to Measure Health Status in People with SSc, J Rheum 2014 [3] Searle SD, et al, A standard procedure for creating a FI, BMC Geriatrics2008 Disclosure of Interests: None declared
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25. FRI0035 INFLAMMATORY ARTHRITIS INDUCED BY IMMUNE-CHECKPOINT INHIBITORS: RESULTS FROM A COMBINED RHEUMATOLOGY/ONCOLOGY OUTPATIENT CLINIC
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Paolo Marchetti, Alain Gelibter, Enrico Cortesi, I. Leccese, Marianna Nuti, Ilaria Grazia Zizzari, Fabrizio Conti, Carlo Perricone, Fulvia Ceccarelli, Guido Valesini, Francesca Di Pietro, Ramona Lucchetti, Andrea Botticelli, and Grazia Sirgiovanni
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Oncology ,medicine.medical_specialty ,business.industry ,Inflammatory arthritis ,Arthritis ,medicine.disease ,Rheumatology ,Prednisone ,Rheumatoid arthritis ,Internal medicine ,Synovitis ,medicine ,Outpatient clinic ,Nivolumab ,business ,medicine.drug - Abstract
Background: Immune checkpoint inhibitors (ICIs) has radically changed the oncology field: the blockade of co-stimulatory molecules on T cells, antigen presenting cells and tumor cells induces unchecked T cell activation with subsequent immune response targeting malignant cells. In the last years, different ICIs have been approved for the treatment of several malignancies. The stimulation of the immune response could be associated with the development of immune-related adverse events (irAEs), potentially involving every organ/system (1). Musculo-skeletal manifestations represent one of the most common irAEs developing during ICIs treatment: up to 40% of treated patients could experience arthralgia or arthritis. Moving from these evidences, the role of the rheumatologist became very important in the management of ICIs treated patients (2). Objectives: To determine the frequency of musculo-skeletal manifestations in patients treated with ICIs in a combined rheumatology/oncology outpatient clinic. Methods: From January 2015 we organised a rheumatology/oncology combined outpatient clinic: all patients starting an ICIs treatment were referred from oncologist to rheumatologist. Data from patients, including demographic features, date of diagnosis, comorbidities and previous and concomitant medications, smoke habit, were collected and registered into a standardized, computerized, electronically filled-in form. All the patients underwent to a physical and laboratory evaluation in order to assess the presence of tender and swollen joints. In case of joint involvement, we assessed disease activity by clinimetric evaluation (DAS28) and ultrasonographic assessment of involved joints (presence of active synovitis as for presence of power Doppler). Moreover, a laboratory evaluation including, ESR, CRP, and autoantibodies (ANA, ACPA, RF) was performed. Results: Seventy-two patients were evaluated (M/F 48/24, median age 66.0 years, IQR 13.0; median disease duration 7 months, IQR 13.0). Concerning malignant disease, 75.1% were affected by non-small cell lung cancer, 15.3% by renal cell carcinoma, 6.9% by melanoma, 2.7% by other malignancies; all patients were treated with anti-PD-1, 67 (93.1%) with nivolumab and 5 (6.9%) with pembrolizumab. During ICIs treatment, 7 patients (9.7%) developed clinically evident synovitis (absolute risk: 0.1; incidence rate 0.01 patients/month): table 1 reports the main features of these 7 patients. According with ACR/EULAR 2010 criteria, two patients could be classified as affected by rheumatoid arthritis (RA). Six patients (85.7%) were treated by prednisone (dosage range 10-12.5mg/daily) or NSAIDs, experiencing a rapid, complete and persistent response. Patient 2, due to resistance to prednisone, was treated by methotrexate 10mg/weekly achieving remission after 6 weeks. Conclusion: The present study represents the first attempt to apply a multidisciplinary approach involving rheumatologists and oncologists in the evaluation of patients treated with ICIs. We found a high absolute risk (10%) to develop synovitis in patients treated by ICIs. Interestingly, the majority of these patients experienced a clinically evident synovitis promptly responding to glucocorticoids and not requiring further DMARDs treatment. This could suggest a peculiar pathogenesis of such ICIs-induced arthritis. References: [1] Calabrese L & Velcheti V, Ann Rheum Diseases 2016; 2. Mooradian MJ et al, Semin Arthritis Rheum 2018 Disclosure of Interests: Fulvia Ceccarelli: None declared, Andrea Botticelli: None declared, Alain Gelibter: None declared, Ilaria Leccese: None declared, Ilaria Zizzari: None declared, Grazia Sirgiovanni: None declared, Francesca Romana Di Pietro: None declared, Ramona Lucchetti: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Enrico Cortesi: None declared, Marianna Nuti: None declared, fabrizio conti: None declared, Paolo Marchetti: None declared, Guido Valesini: None declared
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- 2019
26. AB0379 GENDER DIFFERENCES IN RHEUMATOID ARTHRITIS: EFFECT OF ANTI-TUMOR NECROSIS FACTOR THERAPY
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Cristina Iannuccelli, Bruno Lucchino, Francesca Romana Spinelli, Guido Valesini, Roberta Priori, Chiara Gioia, Manuela Di Franco, and Annarita Vestri
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musculoskeletal diseases ,030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Arthritis ,medicine.disease ,Rheumatology ,Etanercept ,03 medical and health sciences ,Anti-Tumor Necrosis Factor Therapy ,030104 developmental biology ,0302 clinical medicine ,Erythrocyte sedimentation rate ,Rheumatoid arthritis ,Internal medicine ,medicine ,Adalimumab ,Rheumatoid factor ,skin and connective tissue diseases ,business ,medicine.drug - Abstract
Background Rheumatoid arthritis (RA) is more prevalent in women than men (F:M=4:1), due to hormonal, genetic and environment factors. Women present higher disease activity markers as Disease Activity Score-28 (DAS28) and Health Assessment Questionnaire (HAQ), at the onset and after c-DMARDs therapy, without correlation with radiographic damage. Objectives The purpose of this study was to assess gender differences in RA patients after anti- tumor necrosis factor (TNF) α treatment. Methods Ninety-six patients were enrolled at the beginning of anti-TNF α therapy (etanercept and adalimumab). All patients satisfied 1987 and 2010 ACR criteria for RA. They underwent to clinical and clinimetric evaluation at baseline (T0) and after three (T3) and six (T6) months of therapy with: tender and swollen joints, Visual Analogic Scale (VAS) pain, VAS patient and physician, DAS28, Clinical/Simplified clinical disease activity index (CDAI/SDAI) and HAQ. The evaluation of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid Factor (RF) and anti-citrullinated protein antibody (ACPA) was performed in all patients. Results Among these patients, 70 were women and 26 men; 81 patients (58 female, 23 male) started etanercept and 15 adalimumab (12 female, 3 male). They presented a mean age of 56.4 ± 14.5 years (women 55.2 ± 15.4, men 60 ± 11.2) and mean disease duration of 11 ± 6.8 years (woman 11.51 ± 6.3, men 9.6 ± 8.1). Both women and men had a DAS28 reduction after 3 and 6 months therapy (p Conclusion In this study, both women and men had a good response to anti-TNF treatment but women presented worse clinical response. Female gender resulted the only variable associated with DAS28 reduction differences. We could hypothesize that beyond to biological factors, also social contest, daily life and work activity could explain a worse impact of disease on women. References [1] Neovius M, Ann Rheum Dis 2011; [2] O.L. Quintero, et al., Journal of Autoimmunity 2012. [3] M Ahlm aen, Ann Rheum Dis 2010. [4] Jawaheer, et al, The Journal of Rheumatology 2010. [5] Jawaheer, et al, The Journal of Rheumatology 2012. [6] Arnett FC, Arthritis Rheum 1988. [7] Aletaha D, Arthritis Rheum 2010. Disclosure of Interests None declared
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27. FRI0650 A NAILFOLD CAPILLAROSCOPY STUDY IN A COHORT OF PATIENTS WITH ANTI-PHOSPHOLIPID ANTIBODIES
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Guido Valesini, Katia Stefanantoni, Elena Marafioti, Massimiliano Vasile, Valeria Riccieri, Fabrizio Conti, and Fulvia Ceccarelli
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Autoimmune disease ,medicine.medical_specialty ,business.industry ,Autoantibody ,Arthritis ,medicine.disease ,Gastroenterology ,Scleroderma ,Anti phospholipid antibodies ,Internal medicine ,Diabetes mellitus ,Cohort ,medicine ,business ,Nailfold Capillaroscopy - Abstract
Background Nailfold capillaroscopy (NC) is a simple and non-invasive diagnostic technique, able to investigate microvascular features. In subjects with anti-phospholipid autoantibodies (aPL) many different endothelial abnormalities have been described. Objectives We aimed to investigate the role of NC in aPL positive (aPL+) subjects, highlighting the main microvascular alterations, detected by NC. Methods We enrolled 39 patients with primary anti-phospholipids syndrome (pAPS) (32 females, mean age 43 years, mean disease duration 7 years), 47 patients with secondary anti-phospholipis syndrome (sAPS) due to Systemic Lupus Erythematosus (36 females, mean age 44 years, mean disease duration 15.5 years) and 17 aPL+ subjects without any autoimmune disease, defined as aPL carriers (16 females, mean age 42 years). All subjects underwent clinical and laboratory evaluations as well as NC with both characterization of morfological parameters and attribution of a semiquantitative score. Results The main NC findings were: morphological alterations (tortuous, bushy and/or ramified capillary) in 100% patients with pAPS, in 77% sAPS patients and in 88% aPL carriers; microhaemorragies in 56% pAPS patients, in 49% sAPS patients and 24% aPL carriers; enlarged hairpins in 23%, 41% and 18% subjects with pAPS, sAPS and aPL carriers respectively. In 6.3% sAPS patients, an early scleroderma pattern was detected. A NC semiquantitative score 1 was found in 58.9% pAPS patients, in 57.4% sAPS patients and in 70.5% aPL carriers. Among those cases with abnormal NC findings, we found that a higher NC score (>2) was significantly more frequent in pAPS (21.7%) and sAPS (22.2%) patients respect to aPL carrier cases (8.3%) (p We also found, among the main cardiovascular risk factors, that a higher score (1) was significantly associated with the presence of diabetes mellitus in pAPS patients (p Conclusion Our findings show that some NC aspecific abnormalities are more frequently found in aPL positive subjects, mainly in pAPS and sAPS ones. Altough not specific, such NC features seem to be associated with the presence of vascular risk factors. Thus NC could be regarded as a useful tool in order to evaluate microcirculation in aPL positive cases. References [1] Tavakol MEet al, Biomed Res Int2015; 2015: 974530. [2] Maricq HRet al, Arthritis Rheum1980; 23: 183 – 188. [3] Vaz JLPet al, Rheumatology2004;43:1025–7. [4] Sulli A, J Rheum2000;27:1574–6. [5] Aslanidis S, Clin Exp Rheum2011;29:307–9. Disclosure of Interests massimiliano vasile: None declared, Katia Stefanantoni Consultant for: Only 1 scientific advice for Italfarmaco in 2016, Fulvia Ceccarelli: None declared, Elena Marafioti: None declared, fabrizio conti: None declared, Valeria Riccieri: None declared, Guido Valesini: None declared
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28. OP0130 PREMATURE OVARIAN FAILURE IN PATIENTS AFFECTED BY SYSTEMIC LUPUS ERYTHEMATOSUS: A CROSS-SECTIONAL CASE CONTROL STUDY
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Fulvia Ceccarelli, Guido Valesini, Fabrizio Conti, Paola Galoppi, Valeria Orefice, C. Perricone, Francesca Romana Spinelli, Carmelo Pirone, Cristiano Alessandri, Simona Truglia, Giuseppina Perrone, Viviana Antonella Pacucci, and Francesca Miranda
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medicine.medical_specialty ,Lupus anticoagulant ,Systemic lupus erythematosus ,business.industry ,Case-control study ,medicine.disease ,Premature ovarian failure ,Menopause ,Surgical Menopause ,Internal medicine ,Cohort ,medicine ,Amenorrhea ,medicine.symptom ,business - Abstract
Background Women suffering from autoimmune diseases, such as Systemic Lupus Erythematosus (SLE), could develop menopause at a younger age in comparison with healthy population. In particular, a higher frequency of abnormal ovarian function has been described in SLE cohorts1-4. The presence of a cause-effect link between the disease and such modifications remains poorly understood. The role of disease activity and chronic damage, combined with the intake of some drugs, such as cyclophosphamide (CYC), has been suggested2. Objectives We evaluated the age at natural menopause and the prevalence of premature ovarian failure (POF) in a monocentric Caucasian SLE cohort. Additionally, we analyzed the possible association with the disease features. Methods We performed a cross-sectional case-control study, enrolling consecutive SLE women and reporting their clinical and laboratory data. As control group (healthy controls - HC), women without autoimmune diseases were enrolled. By using an interview, gynecological characteristics were investigated in patients and controls: in particular, we registered age at menarche, occurrence and age of menopause, history of hysterectomy. Natural menopause was defined as the absence of menses for at least 12 months in women aged ≥40 years and POF as amenorrhea of at least 12 months in women Results We enrolled 196 Caucasian women with SLE (median age 47.0 years, IQR 16.7; median disease duration 132 months, IQR 180) and 90 HC (median age 49.9 years, IQR 15.0). Ninety-four SLE patients (48.0%) and 26 HC (23.4%) referred a condition of menopause: the median age at occurrence was significantly lower in SLE than HC (47 years, IQR 8.0 versus 50.5 years, IQR 4; P=0.0001). Among the SLE patients, a natural menopause was observed in 70 subjects (74.4%), surgical in 7 (7.4%), iatrogenic in 17 (18.1%). In particular, 13 (13.8%) SLE patients referred the occurrence of menopause after CYC exposure. Excluding SLE patients with surgical menopause, we registered POF in 16 patients (17%); this prevalence was significantly higher in comparison with HC group, in which none of subjects experienced POF (P=0.0001). The comparison between SLE patients developing POF and those with natural menopause history demonstrated a significant higher prevalence of anti-Sm (31.2% versus 10.2%; P=0.0004), anti-RNP (25.0% versus 12.8%; P=0.02), anti-cardiolipin (aCL) IgG/IgM (50.0% versus 26.9%; P=0.0008) and lupus anticoagulant (37.5% versus 17.9%; P=0.002). As expected, a significant more frequent CYC treatment was identified in patients developing POF (56.0% versus 11.0%; P=0.0001). Moreover, POF subjects showed a significant more frequent history of treatment with azathioprine (62.5% versus 30.7; P=0.0001), mycophenolate mofetil (50% versus 20.5%; P=0.0001) and cyclosporine A (37.5% versus 19.2%; P=007). No significant differences were found in terms of clinical manifestations and mean SLICC/ACR damage index (SDI). Conclusion In the present study, we observed a significantly lower age at menopause in SLE patients in comparison with HC; in addition, a significantly higher frequency of POF was observed. POF was associated with a more active disease, in terms of autoantibodies prevalence and use of immunosuppressant drugs. Finally, for the first time, it was found an association between POF and antiphospholipid positivity, suggesting a possible role of these antibodies, in particular aCL, in POF development. References [1] Mayorga J, et al. Lupus 2016 [2] Malheiro, et al. Gynecol Endocrinol 2014 [3] Fatnoon NN, et al. Singapore Med J 2008 [4] Lawrenz, et al. Lupus 2011. Disclosure of Interests Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, Giuseppina Perrone: None declared, Carmelo Pirone: None declared, Carlo Perricone Speakers bureau: BMS; Lilly, Celgene, Sanofi, Simona Truglia: None declared, Francesca Miranda: None declared, viviana antonella pacucci: None declared, francesca spinelli: None declared, Paola Galoppi: None declared, cristiano alessandri: None declared, Guido Valesini: None declared, fabrizio conti: None declared
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- 2019
29. P055 CXCL13 as biomarker for histological involvement in sjogren’s syndrome
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Francesca Arienzo, Joana Campos, Bruna Cerbelli, Benjamin A Fisher, Francesca Barone, Valentina Iannizzotto, Michele Bombardieri, Davide Lucchesi, Charlotte G Smith, Elena Pipi, Guido Valesini, Saba Nayar, Carla Giordano, Roberta Priori, Antonina Minniti, and Serena Colafrancesco
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medicine.medical_specialty ,Chemokine ,Salivary gland ,biology ,medicine.diagnostic_test ,business.industry ,Healthy subjects ,Germinal center ,Gastroenterology ,medicine.anatomical_structure ,Internal medicine ,Biopsy ,medicine ,biology.protein ,Biomarker (medicine) ,Sjogren s ,CXCL13 ,business - Abstract
Career situation of first and presenting author Post-doctoral fellow. Introduction Sjogren’s syndrome (SS) is an autoimmune condition characterised by systemic B cell activation, autoantibody production and ectopic germinal centers (GC) formation within salivary gland (SG). The extent of SG infiltrate has been proposed as biomarker of disease severity. Plasma levels of CXCL13 correlate with GC activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B cell activation. Objectives To evaluate the potential role of CXCL13 as biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n=60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n=49). Both sera and matched paraffin-embedded minor SG biopsy were available. Sicca (n=57) and healthy subjects (HS) (n=19) sera were used as control. CXCL13 gene expression was also assessed in 25 frozen SGs. Results CXCL13 serum levels were higher in SS patients [90.3 (84.2) pg/ml], compared to both sicca [61.9 (38.6) pg/ml), p=0.0005] and HS [36.5 (40.18) pg/ml, p Conclusions Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies. Both serum and tissue expression of CXCL13 correlate with SS histological severity, suggesting a major role of this chemokine in SG lymphocytes recruitment and organization. Disclosure of Interest None declared.
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- 2019
30. Musculoskeletal ultrasound in monitoring response to apremilast in psoriatic arthritis patients: results from a longitudinal study
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Simona Truglia, Francesca Miranda, Ramona Lucchetti, Valeria Riccieri, Rossana Scrivo, Francesca Romana Spinelli, Fabrizio Conti, Manuela Di Franco, Cristiano Alessandri, Enrica Cipriano, Fulvia Ceccarelli, Guido Valesini, and Carlo Perricone
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Male ,Longitudinal study ,medicine.medical_specialty ,Outcome Assessment ,Anti-Inflammatory Agents ,Psoriatic ,Musculoskeletal ultrasound ,SYNOVIAL EFFUSION ,Treatment response ,Joint inflammation ,Ultrasonographic assessment ,Muscle hypertrophy ,03 medical and health sciences ,Psoriatic arthritis ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Outcome Assessment, Health Care ,medicine ,Humans ,030212 general & internal medicine ,Apremilast ,Longitudinal Studies ,Prospective Studies ,Aged ,Ultrasonography ,030203 arthritis & rheumatology ,Tenosynovitis ,Flexor tendon ,business.industry ,Arthritis ,Anti-Inflammatory Agents, Non-Steroidal ,Arthritis, Psoriatic ,General Medicine ,Middle Aged ,medicine.disease ,Thalidomide ,Health Care ,Female ,business ,Non-Steroidal ,medicine.drug - Abstract
Apremilast, PDE4 competitive inhibitor, has been recently introduced in the treatment of adult psoriatic arthritis (PsA) patients, but only preliminary data are available on imaging evaluation. Thus, we evaluated the response to apremilast in PsA patients by ultrasonographic (US) assessment.Thirty-four patients (M/F 7/27; median age 61 years, IQR 15; median disease duration 10 years, IQR 13) treated for polyarticular involvement were longitudinally evaluated. All the patients were assessed at baseline (T0), and after 6 (T1), 12 (T2), and 24 weeks (T3) by DAS28, CDAI, SDAI, and DAPSA. At the same time-points, US assessment was performed in 22 sites (wrists, MCPs, PIPs): synovial effusion/hypertrophy and power Doppler were scored with a semi-quantitative scale (0-3). A total score, corresponding to patient's inflammatory status, was obtained by their sum (0-198). We assessed also the presence of tenosynovitis of flexorWe found a significant reduction in the US inflammatory score values after 6 weeks (T0, median 15 (IQR 11.2); T1, 6 (10.0); P = 0.0002), confirmed at T2 (4.0 (4.0), P = 0.0002) and T3 (4.0 (6.0); P = 0.0003). Finally, US-detected tenosynovitis was observed in 44.1% of patients: a significant improvement in tenosynovitis score was identified at 6 weeks (T0, median 4 (IQR 4); T1, 1 (2); P 0.0001) and maintained at T2 (0 (IQR 1); P 0.0001) and T3 ((IQR 1.25); P 0.0001).Apremilast is able to induce an early and sustained improvement of ultrasonographic inflammatory status at articular and peri-articular level. Key points •Apremilast induces a significant, early, and sustained improvement of inflammatory joint status in psoriatic arthritis patients. •Ultrasonographic assessment is able to monitor articular and peri-articular response to apremilast.
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- 2019
31. Celiac Disease Prevalence is Increased in Primary Sjögren's Syndrome and Diffuse Systemic Sclerosis: Lessons from a Large Multi-Center Study
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Onelia Bistoni, Giulia Mirabelli, Marta Mosca, Alessia Alunno, Salvatore De Vita, Carlo Catassi, Francesco Carubbi, Roberto Giacomelli, Elena Bartoloni, Chiara Baldini, Andrea Doria, Roberto Gerli, Guido Valesini, Franco Franceschini, Armando Gabrielli, Colomba Fischetti, Vittorio Bini, Luca Quartuccio, Roberta Priori, Micaela Fredi, Linda Nalotto, Carlomaurizio Montecucco, and Lorenzo Cavagna
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medicine.medical_specialty ,Tissue transglutaminase ,systemic sclerosis ,Population ,Prevalence ,Lymphoproliferative disorders ,lcsh:Medicine ,Disease ,Gastroenterology ,Article ,Autoimmune thyroiditis ,03 medical and health sciences ,0302 clinical medicine ,systemic lupus erythematosus ,immune system diseases ,Internal medicine ,medicine ,education ,skin and connective tissue diseases ,Subclinical infection ,030203 arthritis & rheumatology ,education.field_of_study ,biology ,business.industry ,lcsh:R ,General Medicine ,Sjögren’s syndrome ,autoimmune rheumatic diseases ,celiac disease ,Endomysium ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,030211 gastroenterology & hepatology ,business - Abstract
Association of celiac disease (CD) with systemic autoimmune diseases (ADs) remains controversial. Awareness of CD in these patients is important to prevent complications, including lymphoproliferative disorders. We evaluated previously diagnosed CD prevalence in systemic lupus erythematosus (SLE), primary Sjö, gren&rsquo, s syndrome (pSS) and systemic sclerosis (SSc) patients in comparison to 14,298 matched controls. All patients were screened for subclinical CD. Data from 1458 unselected consecutive SLE (580), pSS (354) and SSc (524) patients were collected. Previously biopsy-proven CD diagnosis and both CD- and AD-specific features were registered. All patients without previous CD were tested for IgA transglutaminase (TG). Anti-endomysium were tested in positive/borderline IgA TG. Duodenal biopsy was performed in IgA TG/endomysium+ to confirm CD. CD prevalence in AD was compared to that observed in 14,298 unselected sex- and age-matched adults who acted as controls. CD was more prevalent in pSS vs controls (6.78% vs 0.64%, p <, 0.0001). A trend towards higher prevalence was observed in SLE (1.38%, p = 0.058) and SSc (1.34%, p = 0.096). Higher CD prevalence was observed in diffuse cutaneous SSc (4.5%, p &le, 0.002 vs controls). Subclinical CD was found in two SLE patients and one pSS patient. CD diagnosis usually preceded that of AD. Primary SS and SSc&ndash, CD patients were younger at AD diagnosis in comparison to non-celiac patients. Autoimmune thyroiditis was associated with pSS and CD. CD prevalence is clearly increased in pSS and diffuse SSc in comparison to the general population. The association of CD with diffuse but not limited SSc may suggest different immunopathogenic mechanisms characterizing the two subsets. CD screening may be considered in pSS and diffuse SSc in young patients, particularly at the time of diagnosis.
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- 2019
32. Disease Knowledge Index' and Perspectives on Reproductive Issues: a nationwide study on 398 Women with Autoimmune Rheumatic Diseases
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Giuseppe Paolazzi, Roberto Caporali, Marta Mosca, Elena Baldissera, M Rodrigues, Carolina Benigno, Giorgio Pettiti, Roberto Gerli, Cecilia Nalli, Luigi Sinigaglia, Francesca Bellisai, Nazzarena Malavolta, Elena De Stefani, Elena Generali, Maria Favaro, Francesca Dall'Ara, Fabio Basta, Melissa Padovan, Armando Gabrielli, Angela Tincani, Giulia Pazzola, Véronique Ramoni, Laura Andreoli, Armin Maier, Rosario Foti, N Romeo, Francesca Serale, Maddalena Larosa, Carlo Salvarani, Elisa Visalli, I. Prevete, Amelia Ruffatti, Cecilia Beatrice Chighizola, M. Meroni, M Trevisani, Maurizio Cutolo, M Vadacca, Guido Valesini, S. Peccatori, Rossella Reggia, Andrea Doria, Salvatore D'Angelo, Carlo Selmi, Pier Luigi Meroni, Eleonora Valentini, Maria Grazia Lazzaroni, Francesco Paolo Cantatore, Colomba Fischetti, E Vivaldelli, Gian Domenico Sebastiani, Corrado Campochiaro, L Zuliani, Addolorata Corrado, Angela Ceribelli, Valentina Picerno, Chiara Tani, Alessandra Bortoluzzi, E Bartoloni-Bocci, Paola Conigliaro, Roberto Perricone, C Carini, Maria Gerosa, and Carlomaurizio Montecucco
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Adult ,medicine.medical_specialty ,Health Knowledge, Attitudes, Practice ,Adolescent ,Disease ,Risk Assessment ,Severity of Illness Index ,NO ,Unmet needs ,Autoimmune Diseases ,Cohort Studies ,Interviews as Topic ,Young Adult ,Rheumatic diseases ,Rheumatology ,Pregnancy ,Internal medicine ,Surveys and Questionnaires ,Reproductive issues ,medicine ,Humans ,Contraception ,Counselling ,Drugs ,Retrospective Studies ,Practice ,Family Planning Services ,Female ,Italy ,Middle Aged ,Reproductive Health ,Rheumatic Diseases ,business.industry ,Health Knowledge ,Mean age ,Chronic arthritis ,medicine.disease ,Reproductive Issues ,Family medicine ,Attitudes ,Childbearing age ,Rheumatic diseases, Reproductive issues, Pregnancy, Contraception, Drugs, Counselling ,business - Abstract
Objective The reproductive choices of women affected by rheumatic diseases (RD) can be influenced by several factors, including the quality of physician-patient communication. We conducted a survey on reproductive issues aiming at exploring the unmet needs of women with RD during childbearing age. Methods We administered 65 multiple-choice and 12 open-answer questions about pregnancy counselling, contraception, use of drugs during pregnancy and other women reproductive issues to 477 consecutive women with RD aged 18–55 years followed-up in 24 rheumatology centres in Italy. Analysis was restricted to 398 patients who received their diagnosis of RD before the age of 45. According to the RD diagnosis, patients were subdivided into 2 groups: connective tissue diseases (n = 249) and chronic arthritis (n = 149). Results At the time of interview, women in both groups had a mean age of 40 years. Nearly one third of patients in each group declared not to have received any counselling about either pregnancy desire nor contraception. A smaller family size than desired was reported by nearly 37% of patients, because of concerns related to maternal disease in one fourth of the cases. A “Disease Knowledge Index” (DKI) was created to investigate the degree of patients’ information about the implications of their RD on reproductive issues. Having received counselling was associated with higher DKI values and with a positive impact on family planning. Conclusion Italian women of childbearing age affected by RD reported several unmet needs in their knowledge about reproductive issues. Strategies are needed to implement and facilitate physician-patient communication.
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- 2019
33. FRI0040 GENDER DISCREPANCY IN RHEUMATOID ARTHRITIS: PATIENTS’ AND PHYSICIANS’ PERSPECTIVE
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Manuela Di Franco, Francesca Romana Spinelli, Chiara Gioia, Guido Valesini, Ilaria Duca, Alessio Altobelli, Bruno Lucchino, Fabrizio Conti, and Carmelo Pirone
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medicine.medical_specialty ,business.industry ,Visual analogue scale ,Perspective (graphical) ,Training level ,Disease ,medicine.disease ,Affect (psychology) ,Internal medicine ,Rheumatoid arthritis ,Health care ,Global health ,Medicine ,business - Abstract
Background: Rheumatoid Arthritis (RA) is more prevalent among female individuals. Sex and gender differences may influence disease’s progression and prognosis. To date, the influence of physicians’ gender in the evaluation of RA activity is still largely unknown. Objectives: aim of the study was to investigate a possible discrepancy in the assessment of disease activity in RA patients evaluated by male and female physicians. Further aim was to compare patient and evaluator perceptions about disease activity and global health status. Methods: we enrolled consecutive RA patients. Each patient was separately visited by a female and a male rheumatologist of the same age and training level. Tender (TJ) and swollen joints (SJ) count was performed. Global Health (GH), physician’s (E-VAS) and patient’s (P-VAS) disease activity were reported using a visual analogue scale (VAS 0-100). Both examiners were blinded on ESR and CRP. A third rheumatologist assessed disease activity by DAS28-ESR, CDAI and SDAI. Results: we enrolled 154 patients (122 F, 32 M). GH and P-VAS were significantly higher when collected by the female examiner compared to the male one (respectively, 41,1 ± 24,4 vs 36,1 ± 24,3, p Conclusion: subjective measure of global health status and disease activity (GH, P-VAS) are generally higher when collected by a female examiner compared to a male one, especially among female patients. This gender discrepancy in subjective measures could influence the evaluation of disease activity indices; however, this does not affect the probability of being defined in remission. Overall, patients have a higher perception of disease activity compared to the health care providers, and the agreement between physician and patients is only moderate, with female patients having the worst perception. Female physician tend to be more in agreement with the patients’ judgement of disease activity maybe because of a more emphatic setting established by the female health care provider. Disclosure of Interests: None declared
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- 2019
34. Pragmatic language dysfunction in systemic lupus erythematosus patients: Results from a single center Italian study
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Carmelo Pirone, Concetta Mina, Carlo Perricone, Fabrizio Conti, Francesca Romana Spinelli, Fulvia Ceccarelli, Guido Valesini, Cristiano Alessandri, Laura Massaro, and Alfredo Paolo Mascolo
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Male ,Cross-sectional study ,Physiology ,Anticoagulant Therapy ,Social Sciences ,Biochemistry ,Executive Function ,0302 clinical medicine ,Cognition ,Learning and Memory ,Immune Physiology ,Medicine and Health Sciences ,Medicine ,Psychology ,Lupus Erythematosus, Systemic ,Attention ,Social Communication Disorder ,Depression (differential diagnoses) ,Language ,Cognitive Impairment ,Multidisciplinary ,Immune System Proteins ,Cognitive Neurology ,Pharmaceutics ,Middle Aged ,Executive functions ,Adult ,Cross-Sectional Studies ,European Continental Ancestry Group ,Female ,Humans ,Italy ,Cardiovascular Therapy ,Neurology ,Research Article ,medicine.medical_specialty ,Science ,Cognitive Neuroscience ,Immunology ,Systemic Lupus Erythematosus ,Antibodies ,White People ,Autoimmune Diseases ,03 medical and health sciences ,Rheumatology ,Drug Therapy ,Memory ,Neuropsychology ,Internal medicine ,Memory impairment ,Neuropsychological Testing ,Autoantibodies ,030203 arthritis & rheumatology ,Lupus erythematosus ,Lupus Erythematosus ,business.industry ,Systemic ,Cognitive Psychology ,Biology and Life Sciences ,Proteins ,medicine.disease ,Mood disorders ,Autism ,Cognitive Science ,Clinical Immunology ,Clinical Medicine ,business ,030217 neurology & neurosurgery ,Neuroscience - Abstract
BackgroundCognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson's disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far.ObjectivesWe aimed at assessing the PL domain in a Italian monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, the batteria sul linguaggio dell'emisfero destro (BLED). Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features.MethodsForty adult patients affected by SLE, according to the American College of Rheumatology (ACR) criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction.ResultsWe studied 40 Caucasian SLE patients [male (M)/ female (F) 3/37; mean±standard deviation (SD) age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months] and 30 healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 1.3±2.3, mean±SD Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores. As for the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and was significantly more prevalent than memory, executive and visuospatial functions impairment (P = 0.0002, P = 0.0002 and PConclusionIn this study we evaluated for the first time PL in SLE patients finding a dysfunction in almost half of patients. The dysfunction of PL was significantly more frequent than the other domains assessed.
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- 2019
35. Long-term retention rate of anakinra in adult onset Still’s disease and predictive factors for treatment response
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Antonio Vitale, Giulio Cavalli, Serena Colafrancesco, Roberta Priori, Guido Valesini, Lorenza Maria Argolini, Elena Baldissera, Elena Bartoloni, Daniele Cammelli, Giovanni Canestrari, Jurgen Sota, Elena Cavallaro, Maria Grazia Massaro, Piero Ruscitti, Paola Cipriani, Ginevra De Marchi, Salvatore De Vita, Giacomo Emmi, Gianfranco Ferraccioli, Micol Frassi, Roberto Gerli, Elisa Gremese, Florenzo Iannone, Giovanni Lapadula, Giuseppe Lopalco, Raffaele Manna, Alessandro Mathieu, Carlomaurizio Montecucco, Marta Mosca, Ilaria Piazza, Matteo Piga, Irene Pontikaki, Micol Romano, Silvia Rossi, Maurizio Rossini, Elena Silvestri, Chiara Stagnaro, Rosaria Talarico, Angela Tincani, Ombretta Viapiana, Gianfranco Vitiello, Paola Galozzi, Paolo Sfriso, Carla Gaggiano, Donato Rigante, Lorenzo Dagna, Roberto Giacomelli, Luca Cantarini, Vitale, A., Cavalli, G., Colafrancesco, S., Priori, R., Valesini, G., Argolini, L. M., Baldissera, E., Bartoloni, E., Cammelli, D., Canestrari, G., Sota, J., Cavallaro, E., Massaro, M. G., Ruscitti, P., Cipriani, P., De Marchi, G., De Vita, S., Emmi, G., Ferraccioli, G., Frassi, M., Gerli, R., Gremese, E., Iannone, F., Lapadula, G., Lopalco, G., Manna, R., Mathieu, A., Montecucco, C., Mosca, M., Piazza, I., Piga, M., Pontikaki, I., Romano, M., Rossi, S., Rossini, M., Silvestri, E., Stagnaro, C., Talarico, R., Tincani, A., Viapiana, O., Vitiello, G., Galozzi, P., Sfriso, P., Gaggiano, C., Rigante, D., Dagna, L., Giacomelli, R., and Cantarini, L.
- Subjects
musculoskeletal diseases ,0301 basic medicine ,Autoinflammatory disease ,medicine.medical_specialty ,Settore MED/16 - REUMATOLOGIA ,Canakinumab ,Autoinflammatory diseases ,Arthritis ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Still's disease ,medicine ,Pharmacology (medical) ,Adverse effect ,Still disease ,Original Research ,Pharmacology ,Anakinra ,business.industry ,lcsh:RM1-950 ,Innovative biotechnologies ,medicine.disease ,Rash ,Personalized medicine ,Systemic-onset juvenile idiopathic arthritis ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,Interleukin-1 ,Systemic onset juvenile idiopathic arthritis ,Innovative biotechnologie ,030220 oncology & carcinogenesis ,Concomitant ,Autoinflammation ,medicine.symptom ,business ,medicine.drug - Abstract
Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still’s disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043–1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058–0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.
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- 2019
36. CXCL13 as biomarker for histological involvement in Sjögren's syndrome
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Francesca Arienzo, Carla Giordano, Saba Nayar, Michele Bombardieri, Charlotte G Smith, Guido Valesini, Roberta Priori, Serena Colafrancesco, Davide Lucchesi, Joana Campos, Benjamin A Fisher, Antonina Minniti, Elena Pontarini, Valentina Iannizzotto, Massimo Fusconi, Francesca Barone, Elena Pipi, and Bruna Cerbelli
- Subjects
lymphocytes ,0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,Salivary Glands, Minor ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Biopsy ,medicine ,Humans ,Pharmacology (medical) ,CXCL13 ,Retrospective Studies ,030203 arthritis & rheumatology ,B-Lymphocytes ,Immunity, Cellular ,biomarkers ,cytokines and inflammatory mediators ,histopathology ,Sjögren's syndrome ,medicine.diagnostic_test ,Salivary gland ,business.industry ,Autoantibody ,Germinal center ,Middle Aged ,Prognosis ,Chemokine CXCL13 ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Sjogren's Syndrome ,Biomarker (medicine) ,Histopathology ,Female ,Sjogren s ,business ,Biomarkers ,Follow-Up Studies - Abstract
Objectives SS is an autoimmune condition characterized by systemic B-cell activation, autoantibody production and ectopic germinal centres’ formation within the salivary gland (SG). The extent of SG infiltrate has been proposed as a biomarker of disease severity. Plasma levels of CXCL13 correlate with germinal centres’ activity in animal models and disease severity in SS, suggesting its potential use as a surrogate serum marker to monitor local B-cell activation. The aim of this study was to evaluate the potential role of CXCL13 as a biomarker of SG pathology in two independent SS cohorts. Methods 109 patients with SS were recruited at Sapienza University of Rome (Italy) (n = 60), or at Queen Elizabeth Hospital in Birmingham and Barts Health NHS Trust in London (n = 49). Both sera and matched minor SG biopsy were available. Sicca (n = 57) and healthy subjects’ (n = 19) sera were used as control. Results CXCL13 serum level was higher in SS patients compared with controls. Correlations between its serum levels and a series of histomorphological parameters, including size of the aggregates and the presence germinal centres', were observed. Conclusion Our data foster the use of CXCL13 to monitor the extent of local pathology in SS and its validation in longitudinal clinical studies.
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- 2018
37. Renal parenchymal resistance in patients with biopsy proven glomerulonephritis: Correlation with histological findings
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Konstantinos Giannakakis, Fabrizio Conti, Biagio Barbano, Edoardo Rosato, Francesca Di Mario, Anna Rachele Rocca, Antonietta Gigante, Fulvia Ceccarelli, Rosario Cianci, Marzia Simonelli, and Guido Valesini
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Male ,Nephrology ,medicine.medical_specialty ,Pathology ,Biopsy ,Immunology ,030232 urology & nephrology ,Urology ,Arteriolosclerosis ,Renal function ,Kidney ,urologic and male genital diseases ,arteriolosclerosis ,doppler ultrasound ,glomerulosclerosis ,renal pathology ,renal resistive index ,pharmacology ,immunology ,immunology and allergy ,03 medical and health sciences ,Glomerulonephritis ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Letters to the Editor ,030203 arthritis & rheumatology ,Pharmacology ,medicine.diagnostic_test ,business.industry ,Glomerulosclerosis ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Renal pathology ,Kidney Failure, Chronic ,Female ,business ,Glomerular Filtration Rate - Abstract
Renal Doppler ultrasound is increasingly used in nephrology for the evaluation of renovascular disease, allograft dysfunction, and chronic nephropathies. We compared intrarenal hemodynamic parameters to biopsy findings of glomerular sclerosis, tubular atrophy, interstitial fibrosis, crescents, arteriolosclerosis, and clinical variables in 100 patients. A positive correlation exists between renal function and percentage of glomerular sclerosis ( P
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- 2016
38. Anti-SSA/SSB-negative Sjögren's syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution
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Guido Valesini, Elena Bartoloni, Alessia Alunno, Roberto Gerli, Francesco Carubbi, Stefano Bombardieri, L. Corazza, Roberto Giacomelli, Roberta Priori, Serena Colafrancesco, Luca Quartuccio, Nicoletta Luciano, Chiara Baldini, and Salvatore De Vita
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musculoskeletal diseases ,medicine.medical_specialty ,Lymphoma ,Biopsy ,Immunology ,Lymphoproliferative disorders ,Lower risk ,B cell ,Rheumatoid factor ,Sjögren's syndrome ,Humans ,Lymphoproliferative Disorders ,Prevalence ,Risk Factors ,Sjogren's Syndrome ,Immunology and Allergy ,Gastroenterology ,stomatognathic system ,Internal medicine ,medicine ,medicine.diagnostic_test ,business.industry ,Autoantibody ,medicine.disease ,eye diseases ,stomatognathic diseases ,Histopathology ,business ,Anti-SSA/Ro autoantibodies - Abstract
This study aims to compare clinical and laboratory features of patients who, while satisfying the American European Consensus Group (AECG) criteria for primary Sjögren's syndrome (SS), do not present the positivity for anti-Ro/SSA and/or anti-La/SSB, with patients that meet the AECG criteria and are positive for anti-Ro/SSA and/or anti-La/SSB.548 patients were selected based on the following criteria, and exclusion of patients negative for histopathology but positive for anti-Ro/SSA and anti-La/SSB: 1. Fulfilment of the AECG criteria, 2. Performance of minor salivary gland biopsy, 3. Search for anti-Ro/SSA and anti-La/SSB, 4. Absence of hepatitis C virus infection. Univariate and multivariate analyses were performed.Two groups were compared: 342 patients were positive for both the histopathology and for anti-Ro/SSA and/or anti-La/SSB (H-only) and 206 patients were positive for histopathology, but negative for autoantibodies (H+SSA/SSB). The following variables were statistically found to be associated with H+SSA/SSB: younger age at diagnosis (p0.0001), glandular swelling (p=0.01), purpura (p=0.04), leucopoenia (p=0.0001), lymphoma (p=0.002), low C3 (p=0.04), low C4 (p=0.01), hypergammaglobulinemia (p0.0001), ANA (p0.0001), rheumatoid factor (p0.0001), and serum cryoglobulins (p=0.039). ANA positivity (OR 6.9), hypergammaglobulinemia (OR 5.1), positive rheumatoid factor (OR 2.3), and age at diagnosis (OR 0.97) were also selected by multivariate analyses as associated with H+SSA/SSB.Primary SS negative for anti-Ro/SSA and anti-La/SSB antibodies appears to be characterized by a lower risk of lymphoma and by a lower level of B-cell expansion.
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- 2015
39. THU0265 THYMIC STROMAL LYMPHOPOIETIN (TSLP) AS A BIOMARKER OF PRIMARY SJÖGREN’S SYNDROME (PSS) AND RELATED LYMPHOMA: VALIDATION IN INDEPENDENT COHORTS
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Roberta Priori, Chiara Baldini, Roberto Giacomelli, Alessia Alunno, E. Bartoloni Bocci, Luca Quartuccio, Francesco Carubbi, Guido Valesini, Andreas V. Goules, Saviana Gandolfo, Efstathia K. Kapsogeorgou, S. De Vita, Roberto Gerli, Francesco Ferro, A. G. Tzioufas, C. Fabro, and Serena Colafrancesco
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medicine.medical_specialty ,Thymic stromal lymphopoietin ,business.industry ,Immunology ,Complete remission ,Healthy subjects ,medicine.disease ,Serum samples ,Gastroenterology ,General Biochemistry, Genetics and Molecular Biology ,Lymphoma ,Rheumatology ,Internal medicine ,Cohort ,Immunology and Allergy ,Medicine ,Biomarker (medicine) ,Sjogren s ,business - Abstract
Background:Thymic stromal lymphopoietin (TSLP) has been implicated in primary Sjögren’s syndrome (pSS) and related B-cell lymphoproliferation/lymphoma (NHL) by tissue studies on salivary glands (SG) (1). It resulted significantly higher in the serum of pSS patients compared to non-pSS sicca and to healthy subjects, with the highest levels found in NHL.Objectives:The purpose of this work was to confirm that serum TSLP is elevated in pSS by the study of independent cohorts.Methods:Serum TSLP levels were measured by ELISA in 91 pSS patients (F=86, 94.5%; mean age 57.2 years, 25-80) from the Udine cohort (cohort 1, UD), Italy. One additional multicentre cohort (cohort 2) from the Italian SS Study Group (GRISS) was studied, including 125 pSS patients from the Universities of Roma (RO), L’Aquila (L’AQ), Pisa (PI) and Perugia (PG). pSS patients with active NHL (n=12 in cohort 1; n=1 in cohort 2) were excluded from comparative analyses to avoid bias. Secondly, additional serum samples from pSS-related NHL in stable and complete remission, from both cohort 1 and 2, were analysed in a separate subgroup (n = 12). Thirdly, a preliminary evaluation of serum TSLP was performed in pSS patients from a different geographical area (University of Athens, Greece; cohort 3).Results:Cohort 2 included 125 pSS patients (F=114, 91.2%; mean age 58.1 years, 23-84): 124 benign, 1 with NHL. In this cohort, serum TSLP levels were confirmed to be high (mean 30.26 pg/mL, 0.41-95.21) and comparable to cohort 1 (mean 33.81 pg/mL, 0-140.8; p=ns). No difference was found by the separate analysis of pSS from each single Centres (RO n=49, mean 33.21, 1.4-95.21; L’AQ n=34, mean 38.6, 16.31-85.11; PI n=28, mean 20.23, 0.41-56.67; PG n=13, mean 19.39, 1.03-68.38; p=ns), and vs cohort 1 (p=ns). The only patient in cohort 2 with NHL showed serum TSLP of 160.91 pg/mL, comparable to the mean TSLP in the 12 UD pSS-NHL (151.96 pg/mL). Importantly, in pSS-related NHL in stable remission, serum TSLP resulted undetectable (7/13) or detectable at very low levels (6/13) (mean 10.46, 0-38.5), and significantly lower than in benign pSS patients from the two cohorts (n=203, mean 31.48, 0-140.8; p=0.0022). Metachronous samples from one patient, at the stage of NHL activity and then at NHL remission, showed a decrease in TSLP from 128.04 pg/mL to undetectable levels. Finally, TSLP levels were increased also in the Greek cohort (mean 54.9, 26.72-78.95), and significantly higher than the two Italian cohorts (p=0.0085 and pConclusion:Serum TSLP levels are increased in pSS, as herein confirmed in independent cohorts. TSLP might be important in the disease pathophysiology and mirrors the course of pSS-related B-cell lymphoproliferation itself. It may thus represent a novel important biomarker.References:[1]Gandolfo S. et al, Clin Exp Rheumatol. 2019 May-Jun;37 Suppl 118(3):55-64.Disclosure of Interests:Saviana Gandolfo: None declared, Cinzia Fabro: None declared, Serena Colafrancesco: None declared, Francesco Carubbi Speakers bureau: Francesco Carubbi received speaker honoraria from Abbvie and Celgene outside this work., Francesco Ferro: None declared, Elena Bartoloni Bocci: None declared, Efstathia Kapsogeorgou: None declared, Andreas Goules: None declared, Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Roberta Priori: None declared, Alessia Alunno: None declared, Guido Valesini: None declared, Roberto Giacomelli Grant/research support from: Actelion, Pfizer, Speakers bureau: Abbvie, Roche, Actelion, BMS, MSD, Ely Lilly, SOBI, Pfizer, Roberto Gerli: None declared, Chiara Baldini: None declared, Athanasios Tzioufas: None declared, Salvatore De Vita Consultant of: Roche, Human Genome Science, Glaxo Smith Kline and Novartis
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- 2020
40. FRI0376 EFFECT OF CARBAMYLATED LOW-DENSITY LIPOPROTEINS ON BONE CELLS HOMEOSTASIS
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M. Di Franco, Martina Leopizzi, Tania Colasanti, V. Di Maio, Guido Valesini, Fabrizio Conti, F.R. Spinelli, Bruno Lucchino, and Cesare Alessandri
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medicine.medical_specialty ,biology ,business.industry ,Immunology ,Acid phosphatase ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,Uremia ,Endocrinology ,medicine.anatomical_structure ,Rheumatology ,Osteoprotegerin ,RANKL ,Osteoclast ,Internal medicine ,Bone cell ,medicine ,biology.protein ,Immunology and Allergy ,Alkaline phosphatase ,business - Abstract
Background:Carbamylation is a post-translational modification occurring under several conditions such as uremia, smoking and chronic inflammation as in rheumatoid arthritis (RA). Low-density lipoproteins (LDL) represent a target of carbamylation. Carbamylated-LDL (cLDL) have an increased inflammatory and atherogenic potential. Growing evidence supports an influence of modified lipids on bone cells homeostasis. However, the role of cLDL on bone cells physiology is still unknown.Objectives:Considering the rate of carbamylation and the role of anti-carbamylated proteins antibodies as markers of erosive disease in RA, the purpose of this study is to investigate the effect of cLDL on bone homeostasis.Methods:In-vitrocarbamylation of LDL was performed as previously described by Ok et al. (Kidney Int. 2005). Briefly, native LDL (nLDL) were treated with potassium cyanate (KOCN) for 4 hours, followed by excessive dialysis for 36 hours to remove KOCN. Both osteoclasts (OCs) and osteoblasts (OBLs) were treated at baseline with 20 μg/ml, 100 μg/ml and 200 μg/ml of cLDL or nLDL. To induce osteoclast differentiation, CD14+ monocytes were isolated from peripheral blood of healthy donors by magnetic microbeads separation and then cultured on a 96-wells plate in DMEM media supplemented with RANKL and M-CSF. After 10 days cells were fixed, stained for tartrate-resistant acid phosphatase (TRAP), a marker of OC differentiation, and counted. OBLs were isolated from bone specimens of 3 patients who had undergone to knee or hip arthroplasty for osteoarthritis and treated for 5 days with different concentrations of cLDL and nLDL. OBLs were fixed and stained for alkaline phosphatase positive activity (ALP), a marker of osteogenic differentiation. Total RNA was extracted from cell lysates. Copies of single-stranded complementary DNA (cDNA) were synthesized and analyzed by real-time PCR to evaluate RANKL and Osteoprotegerin (OPG) mRNA expression levels.Results:In OCLs culture, cLDL significantly decreased the number of OC compared to untreated cells (200 μg/ml p=0,0015) and nLDL treated cells (200 μg/ml p= 0,011; 20 μg/ml p= 0,0014) (Fig 1). Moreover, treatment with cLDL induced an increase of not terminally differentiated OCs, reduced dimensions of OCs, less intense TRAP staining and vacuolization (Fig 2). In OBLs culture, cLDL (20, 100 μg/ml) significantly reduced the ALP activity of OBLs compared with untreated cells (pFig 1.Fig 2.Fig 3.Fig 4.Conclusion:cLDL induce a significant depression of OC and OBL differentiation. Moreover, cLDL increase RANKL expression in OBL, unbalancing bone tissue turnover towards bone resorption. Accordingly, cLDL could be implicated in the bone loss characterizing several conditions associated to an increased carbamylation, such as RADisclosure of Interests:Bruno Lucchino: None declared, Martina Leopizzi: None declared, Tania Colasanti: None declared, Valeria Di Maio: None declared, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Manuela Di Franco: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly
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- 2020
41. SAT0228 PREGNANCY OUTCOME IN SYSTEMIC LUPUS ERYTHEMATOSUS: A MONOCENTRIC COHORT ANALYSIS
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Giuseppina Perrone, V. A. Pacucci, Fabrizio Conti, F.R. Spinelli, Cesare Alessandri, Simona Truglia, A. Selntigia, Carmelo Pirone, Carlo Perricone, Fulvia Ceccarelli, and Guido Valesini
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medicine.medical_specialty ,Pregnancy ,business.industry ,Immunology ,Context (language use) ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Miscarriage ,Internal medicine ,Cohort ,Immunology and Allergy ,Gestation ,Medicine ,Medical history ,business ,Cohort study - Abstract
Background:Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, affecting prevalently women in childbearing age. Thanks to pre-gestational counseling and multi-disciplinary approach, adopted in daily clinical practice, SLE patients are experiencing even more uncomplicated pregnancies.Objectives:Here, we evaluated pregnancy outcome in a large SLE cohort, compared to a control group including pregnant women without autoimmune diseases.Methods:Pregnant SLE patients (diagnosis made according to ACR 1997 criteria) were included in the present study, conducted in the context of a joint rheumatology/gynecology multi-disciplinary team. For each patient we collected demographic information, medical history, treatments, disease activity (SLEDAI-2K) chronic damage (SLICCdamage index), clinical and laboratory data, including serum complement level and autoantibodies. Pregnancy outcomes were reported longitudinally as well as disease relapses occurring during pregnancy and puerperium. Flares were defined as new onset or worsening disease-related manifestation in any organ/system.Results:Since 2008, 70 consecutive pregnancies occurred in 50 SLE patients [(median age at diagnosis 25 years (IQR 12.2), median age at first pregnancy 33 years (IQR 7), median disease duration 72 months (IQR 120)]. As controls, we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases [(median age 31 years (IQR 9)]. Table 1 reports the obstetric, fetal and neonatal outcomes of SLE patients compared to control group. A positive outcome in terms of live born infants was experienced in 88.6% of SLE pregnancies and in 88% of control group (p=NS). There were no statistically significant differences in any of the pregnancy outcomes evaluated; however, the percentage of small for gestational ages (SGA) was significantly higher in SLE group (22.8%versus11.0% P=0.003). A statistical association was found between SGA and positivity for anti-dsDNA, anti-SSA ed anti-SSB (p=0.0001, p=0.01, p=0.04 respectively). Miscarriage was significantly associated with disease-related serologic abnormalities [anti-dsDNA (p=0.0001), low C3 (p=0.0001) and low C4 (p=0.006)] and past smokinghabitus(p=0.0001); preterm birth was associated with anti-dsDNA, anti-CL and anti-B2GPI (p=0.001, p=0.0005, p=0.01 respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium (44.3%). Figure 1 reports SLE relapses divided according to organ involvement. Flare during pregnancy was associated with positivity for anti-SSA (p=0.001), anti-SSB (p=0.01) and a-CL (p=0.006), whilepuerperiumrelapses were associated with previous renal involvement (p=0.0005), flare during pregnancy (p=0.01) and chronic damage (p=0.0001).Table 1.Pregnancy outcomes in 50 SLE and 100 controls.LES(Pregnancies N=70)Controls(Pregnancies N=100)POBSTETRIC OUTCOMEPreterm birth N/%18/25.719/19NSGestational hypertension N/%5/7.13/3NSGestational diabetes N/%5/7.15/5NSPre-eclampsia N/%2/2.91/1NSFETAL OUTCOMEMiscarriages N/%8/11.412/12NSPR interval elongation N/%4/6.4––IUGR N/%3/51/1NSNEONATAL OUTCOMESGA< 10° centile N/%16/22.811/110.003Weight at birth median-I.Q.R.2850-6883250-8140.003Apgar 1’ median-I.Q.R.8-18-1NSApgar 5’ median-I.Q.R.9-110-1NSFigure 1.Disease flares during and after 70 SLE pregnancies divided according to organ involvement.Conclusion:The present study confirms the role of pre-gestational counseling and a multi-disciplinary approach in the outcome of SLE pregnancies. Moreover, the high prevalence of disease relapse even more justifies the need for a combined rheumatology/gynecology multi-disciplinary approach.Disclosure of Interests:Carmelo Pirone: None declared, Fulvia Ceccarelli: None declared, Aikaterini Selntigia: None declared, Carlo Perricone: None declared, Simona Truglia: None declared, viviana antonella pacucci: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Giuseppina Perrone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
42. THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS
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Fulvia Ceccarelli, Guido Valesini, Carlo Perricone, Giulio Olivieri, F. Natalucci, Ramona Lucchetti, Cristiana Barbati, Valeria Orefice, Fabrizio Conti, Cesare Alessandri, F.R. Spinelli, and Enrica Cipriano
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Autoimmune disease ,medicine.medical_specialty ,business.industry ,Immunology ,Lupus nephritis ,Disease ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Disease activity ,chemistry.chemical_compound ,Rheumatology ,chemistry ,Internal medicine ,Cohort ,medicine ,Immunology and Allergy ,Caffeine intake ,B-cell activating factor ,Caffeine ,business - Abstract
Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: 376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
43. FRI0134 EFFECT OF JAK INHIBITORS ON PAIN AND QUALITY OF LIFE IN RHEUMATOID ARTHRITIS PATIENTS
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Cesare Alessandri, Valeria Riccieri, C. Garufi, I. Duca, Fulvia Ceccarelli, Guido Valesini, Fabrizio Conti, S. Mancuso, F.R. Spinelli, Rossana Scrivo, Roberta Priori, and M. Di Franco
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medicine.medical_specialty ,Tofacitinib ,biology ,business.industry ,Immunology ,C-reactive protein ,Health condition ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Quality of life ,Interquartile range ,Internal medicine ,Rheumatoid arthritis ,Cohort ,medicine ,biology.protein ,Immunology and Allergy ,Residual pain ,business - Abstract
Background:Pain control is considered a treatment priority from most patients with Rheumatoid Arthritis (RA). Despite the treat to target approach, residual pain is commonly reported by patients with RA. Treatment with JAK inhibitors (JAKi) has been associated to a rapid control of pain.Objectives:To investigate the effect of JAKi on pain and quality of life in a mono-centric real-life clinical setting.Methods:Patients candidate to baricitinib or tofacitinib were evaluated at baseline and after 12 and 24 weeks of treatment. Disease activity was assessed by Disease Activity Score (DAS)28 with C reactive protein (CRP). A reduction of ≥ 50% of pain visual-analogue scale (VAS) 0-100 mm was recorded as “very much improved, substantially improved” (1). Pain VAS score ≤ 10 mm was considered “no/limited pain” (2). Patients’ satisfaction was assessed by the Patient Acceptable Symptom State question (3). Data were expressed as mean (SD) or median (interquartile range) according to the variables’ distribution. Mann Witney test was use and p values Results:Overall 108 patients started a JAK inhibitor (baricitinib n=67, tofacitinib n=41). Eighty-four patients (baricitinib n=51; tofacitinib n=33) were followed-up for at least 3 months and were included in the analysis. Table 1 summarizes demographic and clinical characteristic of the cohort. After 12 and 24 weeks of treatment we detected a significant reduction of DAS28 compared with baseline [from 4.7 (1.5) to 3.2 (1.7) 2.9 (1.5) and 2.7 (1.1), respectively; pConclusion:JAK inhibitors baricitinib and tofacitinib induce a rapid improvement of disease activity driven both by pain and inflammation control. Even if no/limited pain was described only by one third of the patients, most of them reported a rapid and sustained reduction of pain accounting for the achievement of a satisfactory health condition.References:[1]Dworkin RH et al. Pain 2008; 9:105–121.[2]Well GA et al. J Rheumatol 2005; 32:2016–2024.[3]Heiber T et al. Ann Rheum Dis 2008; 67:967-71.Baricitinib (n=51)Tofacitinib (n=33)PF:M43: 826:7nsAge, mean (SD)59±1260±12nsDisease duration, mean (SD)163±101170±112nsBaseline DAS28(PCR), median (IQR)4.7 (4-5.6)4.7 (4.3-5.4)nsConcomitant methotrexate, n (%)27 (52.9)8 (24.2)Daily prednisone dose, median (IQR)5 (2.5-9.5)5 (1.88-9.9)nsN° of previous csDMRADs, median (IQR)3 (1-4)2.5 (2-3)nsN° of previous bDMRADs, median (IQR)2 (1-4)1 (0-2.5)nsDisclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Silvia Mancuso: None declared, Ilaria Duca: None declared, cristiano alessandri Grant/research support from: Pfizer, Manuela Di Franco: None declared, Roberta Priori: None declared, Valeria Riccieri: None declared, Rossana Scrivo: None declared, Guido Valesini: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi
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- 2020
44. Correspondence on 'Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation’ by Braaten et al
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Ramona Lucchetti, Andrea Botticelli, Alain Gelibter, Enrico Cortesi, Fabrizio Conti, Paolo Marchetti, I. Leccese, Fulvia Ceccarelli, and Guido Valesini
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030203 arthritis & rheumatology ,0301 basic medicine ,medicine.medical_specialty ,business.industry ,Inflammatory arthritis ,medicine.medical_treatment ,Immunology ,Arthritis ,Context (language use) ,Immunotherapy ,medicine.disease_cause ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Autoimmunity ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Internal medicine ,Synovitis ,medicine ,Immunology and Allergy ,Outpatient clinic ,business - Abstract
We read with interest the study published by Braaten and colleagues, analysing the long-term outcomes of 60 patients developing persistent inflammatory arthritis (IA) after immune checkpoint inhibitors (ICIs) cessation. The most relevant result of the study was the presence of active arthritis in more than half of the patients at the last follow-up visit.1 We report here our experience in the context of a joint oncology/rheumatology outpatient clinic, in order to evaluate the risk of developing IA in patients treated by anti-PD1 drugs. During 1-year period, we consecutively assessed all the adult patients candidate to anti-PD1 treatment, referring to the Oncology Unit at the Sapienza University of Rome. After treatment starts, in the case of musculoskeletal manifestations, patients were referred to the Sapienza Arthritis Center, Rheumatology Unit, Sapienza University of Rome. Arthritis was defined as the occurrence of at least one episode of clinical synovitis, with morning stiffness lasting at least 30 min. …
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- 2020
45. Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients
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Carlo Perricone, Valeria Riccieri, Ramona Lucchetti, Rossana Scrivo, I. Bartosiewicz, Yehuda Shoenfeld, S Fais, Germano Orrù, Fulvia Ceccarelli, M Olivieri, Guido Valesini, Antonella Polimeni, Cesare Alessandri, Fabrizio Conti, M. Di Franco, Roberta Priori, E Martino, Andrea Pilloni, and Marta Vomero
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rheumatoid arthritis ,Male ,Prevalence ,microbiome ,Osteoarthritis ,Gastroenterology ,Arthritis, Rheumatoid ,Cohort Studies ,0302 clinical medicine ,Rheumatoid ,Bacteroidaceae Infections ,Immunology and Allergy ,medicine.diagnostic_test ,biology ,Microbiota ,Middle Aged ,Italy ,Erythrocyte sedimentation rate ,Rheumatoid arthritis ,Disease Progression ,Female ,Porphyromonas gingivalis ,Adult ,medicine.medical_specialty ,porphyromonas gingivalis ,disease activity ,Immunology ,03 medical and health sciences ,Tongue ,Internal medicine ,medicine ,Vitamin D and neurology ,Humans ,Periodontitis ,Aged ,030203 arthritis & rheumatology ,business.industry ,Arthritis ,Case-control study ,030206 dentistry ,Original Articles ,medicine.disease ,biology.organism_classification ,Biofilms ,Case-Control Studies ,business - Abstract
Summary Several studies have suggested a link between human microbiome and rheumatoid arthritis (RA) development. Porphyromonas gingivalis seems involved in RA initiation and progression, as supported by the high occurrence of periodontitis. In this case–control study, we analysed tongue P. gingivalis presence and quantification in a large healthy and RA cohort. We enrolled 143 RA patients [male/female (M/F) 32/111, mean ± standard deviation (s.d.), age 57·5 ± 19·8 years, mean ± s.d. disease duration 155·9 ± 114·7 months); 36 periodontitis patients (M/F 11/25, mean ± s.d., age 56 ± 9·9 years, mean ± s.d. disease duration 25·5 ± 20·9 months); and 57 patients (M/F 12/45, mean ± s.d., age 61·4 ± 10·9 years, mean ± s.d. disease duration 62·3 ± 66·9 months) with knee osteoarthritis or fibromyalgia. All subjects underwent a standard cytological swab to identify the rate of P. gingivalis/total bacteria by using quantitative real-time polymerase chain reaction. The prevalence of P. gingivalis resulted similarly in RA and periodontitis patients (48·9 versus 52·7%, P = not significant). Moreover, the prevalence of this pathogen was significantly higher in RA and periodontitis patients in comparison with control subjects (P = 0·01 and P = 0·003, respectively). We found a significant correlation between P. gingivalis rate in total bacteria genomes and disease activity score in 28 joints (DAS28) (erythrocyte sedimentation rate) (r = 0·4, P = 0·01). RA patients in remission showed a significantly lower prevalence of P. gingivalis in comparison with non-remission (P = 0·02). We demonstrated a significant association between the percentage of P. gingivalis on the total tongue biofilm and RA disease activity (DAS28), suggesting that the oral cavity microbiological status could play a role in the pathogenic mechanisms of inflammation, leading to more active disease.
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- 2018
46. A Monocentric Cohort of Obstetric Seronegative Anti-Phospholipid Syndrome
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Simona Truglia, Agostina Longo, Carlo Perricone, Caterina De Carolis, Maurizio Sorice, Gloria Riitano, Valeria Manganelli, Cristiano Alessandri, Antonella Capozzi, Tina Garofalo, Roberta Misasi, Guido Valesini, Francesca Romana Spinelli, S. Mancuso, Sara De Carolis, Serena Recalchi, and Fabrizio Conti
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lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,Immunology ,Vimentin ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,anti-phosphatidylserine/prothrombin ,Antiphospholipid syndrome ,Internal medicine ,Immunology and Allergy ,Medicine ,In patient ,anti-phospholipid syndrome ,seronegative anti-phospholipid syndrome ,anti-vimentin/cardiolipin ,thin-layer chromatography ,Original Research ,030203 arthritis & rheumatology ,biology ,business.industry ,medicine.disease ,Anti-Phospholipid Syndrome ,Cohort ,biology.protein ,Antibody ,business ,lcsh:RC581-607 ,030215 immunology - Abstract
The present study was conducted to diagnose obstetric anti-phospholipid syndrome (OAPS) in patients with clinical signs suggestive of anti-phospholipid syndrome (APS), but persistently negative for conventional anti-phospholipid antibodies (aPL). Sera from 61 obstetrical seronegative APS (SN-APS) patients were analyzed for anti-cardiolipin antibodies (aCL) using thin-layer chromatography (TLC)-immunostaining, for anti-cardiolipin/vimentin antibodies (aCL/Vim), anti-phosphatidylserine/prothrombin antibodies, IgA anti-β2glycoprotein I antibodies (aβ2GPI), and IgA aCL antibodies by enzyme-linked immunosorbent assay. Taken together, our findings show that in 50 out of 61 SN-APS (81.9%) at least one aPL/cofactor antibody was detected using the assays under test. Results revealed that 76% of SN-APS patients resulted positive for aCL by TLC-immunostaining, 54% for aCL/Vim, 12% for aPS/PT, 4% for IgA aβ2GPI, and 2% for IgA aCL. Thirty-five out of 61 patients were followed up and the tests were repeated on two occasions, at least 12 weeks apart. Twenty-six out of 35 SN-APS (74.3%) were positive at least one non-conventional test; only 2 patients (5.7%) did not confirm the positivity to the second test. These findings suggest that non-conventional tests, mainly aCL/Vim and aCL detected by TLC-immunostaining, seem to be the most sensitive approaches for finding out aPL in patients with obstetric SN-APS. The use of these tests can be useful for accurate and timely diagnosis of patients with obstetrical APS who are negative for conventional laboratory criteria markers.
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- 2018
47. FRI0260 Polymorphisms of stat4 and mir146a predict the achievement of 5 years remission in patients with systemic lupus erythematosus
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F.R. Spinelli, Fabrizio Conti, Carlo Perricone, Andrea Latini, Fulvia Ceccarelli, Giuseppe Mettola, Cesare Alessandri, Guido Valesini, I. Leccese, Cristina Politi, Cinzia Ciccacci, Giuseppe Novelli, and Paola Borgiani
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Oncology ,Autoimmune disease ,medicine.medical_specialty ,business.industry ,Single-nucleotide polymorphism ,medicine.disease ,Pathogenesis ,Immune system ,immune system diseases ,Internal medicine ,Cohort ,Genotype ,Medicine ,skin and connective tissue diseases ,business ,STAT4 ,Genotyping - Abstract
Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex pathogenesis in which genes and environmental factors interact leading to a protean clinical picture. Treat-to-target recommendations have identified ‘remission’ as a target in SLE, since achievement of remission improves the outcome and is associated with decreased damage progression. Nonetheless, predicting factors for the achievement of remission are lacking. It is likely that genes associated with SLE pathogenesis may influence the disease course. Objectives Thus, our aim was to analyse previously identified loci associated with SLE in a cohort of SLE patients to evaluate their influence on remission achievement. Methods We recruited 117 Italian SLE patients. A panel of 34 SNPs in 19 genes involved in immune response, autophagy and inflammation, was selected. SNPs genotyping was performed by allelic discrimination assay by TaqMan assays (Applied Biosystems, Foster City, CA, USA) and ABI PRISM 7000. The main clinical/laboratory features (including injury index and disease activity) were collected on an electronic platform. Remission was defined according to Zen et al.1 and evaluated over 5 years. A genotype/phenotype correlation analysis was performed. Results The variant alleles of rs7574965 (STAT4) (p Conclusions We describe for the first time the contribution of STAT4 and MIR146a SNPs as predicting factors for the achievement of 5 years remission in SLE. No genetic study has been performed so far in SLE, while a genetic profile of patients may be useful to predict the disease outcome. Reference [1] Zen, et al. Ann Rheum Dis. 2017Mar;76(3):562–565. Disclosure of Interest None declared
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- 2018
48. FRI0321 Survival rate and causes of withdrawal of belimumab treatment in sle in a real life setting
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Laura Massaro, Fulvia Ceccarelli, Guido Valesini, F.R. Spinelli, Cesare Alessandri, L. Novelli, Fabrizio Conti, Carlo Perricone, Francesca Miranda, Simona Truglia, and F. Morello
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medicine.medical_specialty ,business.industry ,Hydroxychloroquine ,Azathioprine ,Belimumab ,Prednisone ,Internal medicine ,Concomitant ,medicine ,Adverse effect ,business ,Survival rate ,Survival analysis ,medicine.drug - Abstract
Background Systemic Lupus Erythematosus (SLE)is a chronic disease requiring long-term treatment. Even though immunosuppresive therapies improved the survival rate,a great percentage of SLE patients exhibit a persistently active disease, or disease flares. Belimumab (BLM), is currently the only biological drug approved for the treatment of active SLE patients not responding to standard of care, without active kidney or neuropsychiatric (NP)involvement. Objectives Aim of the study was to analyse 36 months survival of BLM treatment, causes of withdrawal in a monocentric cohort of SLE patients followed-up in a daily practice setting. Methods The study was proposed to all the patients strarting BLM. After the informed consent was obtained, demographic, clinical and serological data, indication to BLM and concomitant therapies were registered. At baseline and at 6,12,24,36 months of follow-up, disease activity (SLEDAI 2K), DAS28, C3 and C4 levels, anti-dsDNA status and weekly dose of glucocorticoids were recorded. Data were expressed as median-interquartile range; after 6,12,24,36 months, differences in all parameters compared to baseline were evaluated (Student t test)The treatment survival was evaluated by Kaplan-Meier analysis. P value Results We enrolled 39 Caucasian individual, 38 females, 1 male, with median age of 43 (IQR 7.5) years and median disease duration 14.5 (5.5) years. Indications for starting BLM were: mucocutaneous involvement (n=11,28%), arthritis (n=25,64%), systemic symptoms (n=3,7%) and lung involvement (1 pt,2%). At baseline, all the patients were taking PDN;97% hydroxychloroquine,23% mycophenolate mofetil,23% azathioprine, 5% cyclosporine, 7% methotrexate and 2% thalidomide. Table 1 summarises trend of SLEDAI 2K, C3 and C4, DAS28 (for articular involvement), prednisone dose and percentage of patients positive for anti-dsDNA during the follow-up. Fourteen out of the 39 patients (35.8%) reached 12 months of observation and only 4 the 24 months, 3 the 36 months. Figure 1 shows the survival curve of Belimumab. In 8 patients (20%) adverse events were the cause of BLM withdrawal (severe infection in one patient, severe bradychardia in one and acute infusion reaction in another one). In 4 patients (10%) BLM was discontinued for lack of efficacy(articular and skin manifestations)after 4, 8, 12 and 23 months respectively; in 6 patients (15%) for loss of efficacy; one patient developed a severe NP flare after 2nd BLM infusion and was admitted in our hospital for depression. One patient was lost during the follow-up. Two patients withdrew BLM therapy to plan a pregnancy. We found significant reduction of PDN week levels, and improvement of C4 and aDNA levels at T6; as for disease activity, we found significant reduction of DAS28 at T6, and of SLEDAI-2k at T6 and T12. Conclusions In our monocentric cohort of SLE patients, BLM demonstrated to be effective on disease activity and serology and led to a significant decrease of glucocorticoids dose; the main causes of BLM withdrawal were adverse events or disease flares. Disclosure of Interest None declared
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- 2018
49. OP0091 Cxcl10/cxcl11 serum measurement as potential predictor of systemic sclerosis
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Valeria Riccieri, Clara Crescioli, Massimiliano Vasile, Valeria Raparelli, Stefania Basili, Andrea Lenzi, F. Del Galdo, Cristina Antinozzi, Clarissa Corinaldesi, and Guido Valesini
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medicine.medical_specialty ,business.industry ,Autoantibody ,Arthritis ,medicine.disease ,Gastroenterology ,Rheumatology ,Basal (phylogenetics) ,Fibrosis ,Internal medicine ,medicine ,Biomarker (medicine) ,CXCL10 ,Endothelial dysfunction ,business - Abstract
Background Systemic sclerosis (SSc), amongst autoimmune rheumatic disorders, shows a heterogeneous and unpredictable course from stable/mild involvement to progressive/late stage, when irreversible multiorgan fibrosis occurs.1 Early SSc diagnosis remains a clinical challenge; a delay in diagnosis leads, in turn, to therapy delay and more severe patient disability.2 3 Earliest vascular immune-mediated alterations are critical in SSc, which, indeed, has been referred to as a ‘vascular’ disease.4 Recognition of biomarker(s) involved in earliest vascular derangements might represent a clinical tool potentially useful for therapeutic approach. Blood level of chemokines IFNγ-inducible protein 10 (IP-10/CXCL10) and IFN-inducible T cell alpha chemoattractant (I-TAC/CXCL11), both involved in endothelial dysfunction, has been shown to associate with worse SSc prognosis.5,6 Objectives To investigate possible modifications of circulating CXCL10/CXCL11 in the shift from very early diagnosis of SSc (VEDOSS), when vasculopathy and fibrosis are still at very low degree, to definite SSc. Associations between chemokines and capillaroscopic pattern, autoantibody positivity were evaluated. Methods Multiplatform luminex technology was used to analyse CXCL10/CXCL11 in total 62 sera, 34 from VEDOSS and 28 from SSc patients, fulfilling the new ACR/EULAR 2013 classification criteria; none of the subjects were treated for SSc. Within VEDOSS group, we selected 29 sera of subjects with follow up (40.67±5.46 months) and, for each patient of this subcohort, chemokine levels were assessed at follow up (T1) and compared with basal level (T0). Appropriate tests were used for sample distribution and statistical analysis. Results Serum CXCL10/CXCL11 were significantly lower in all VEDOSS (CXCL10: 236.00±40.09 pg/ml; CXCL11: 38.00±6.97 pg/ml) vs all SSc sera (CXCL10: 633.90±97.60 pg/ml; CXCL11: 267.70±76.10 pg/ml; p Conclusions CXCL10/CXCL11 blood level measurement in VEDOSS patients potentially represents a noninvasive biomarker associated with vascular modifications – as shown by capillaroscopic pattern – predictive of SSc. References [1] Domsic RT, et al. Ann Rheum Dis2011Jan;70(1). [2] Pattanaik D, et al. Front Immunol2015;6:272. [3] Khanna D, et al. Best Pract Res Clin Rheumatol2010Jun;24(3). [4] Matucci-Cerinic M, et al. Arthritis Rheum2013Aug;65(8). [5] Antonelli A, et al. Rheumatology (Oxford)2008Jan;47(1). [6] Liu X, et al. Arthritis Rheum2013Jan;65(1). Disclosure of Interest None declared
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- 2018
50. S5A:6 Anti-carbamylated proteins antibodies in sle patients with joint involvement: a possible new biomarker for erosive damage
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G Capalbo, F.R. Spinelli, Carlo Perricone, Tania Colasanti, Fabrizio Conti, Cesare Alessandri, Laura Massaro, Fulvia Ceccarelli, Guido Valesini, M. Pendolino, Rita Mancini, Enrica Cipriano, and F. Natalucci
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medicine.medical_specialty ,business.industry ,Arbitrary unit ,Autoantibody ,Arthritis ,medicine.disease ,Gastroenterology ,Internal medicine ,Synovitis ,Rheumatoid arthritis ,medicine ,Biomarker (medicine) ,Rheumatoid factor ,skin and connective tissue diseases ,business ,Blood drawing - Abstract
Purpose The concept of non-erosive arthritis in Systemic Lupus Erythematosus (SLE) changed during the last years, thanks to more sensitive imaging techniques, such as ultrasonography (US), allowing the identification of erosive damage in up to 47% of patients. The predictive role of Rheumatoid Arthritis (RA)-specific auto antibodies has been investigated. In particular, anti-citrullinated peptide antibodies (ACPA) have been identified in about 50% of SLE patients with x-Ray detected erosive arthritis. More recently, anti-carbamylated proteins antibodies (anti-CarP) have been demonstrated in seronegative RA, with a significant association with erosive damage. In the present cross-sectional study, we assessed the association between anti-CarP and erosive damage in a cohort of SLE patients with joint involvement. Methods We evaluated 152 SLE patients (1997 ACR criteria; M/F 11/141, mean ±SD age 46.4±11.3 years, mean ±SD disease duration 144.9±110.5 months) with joint involvement. Clinical and laboratory data were collected in a standardised computerised electronically filled form. All patients underwent blood draws to detect Rheumatoid Factor (RF) and ACPA, by using commercial ELISA kits, and anti-CarP by home-made ELISA (results were expressed in arbitrary units (AU)/ml and values above 340 IU/ml were considered positive). US was performed to assess the bone surfaces of metacarpophalangeal and proximal interphalangeal. At each joint, according with OMERACT definition, the presence of erosions was registered with a dichotomous value (0/1), obtaining a total score, ranging from 0 to 20. Results The anti-CarP prevalence was 28.3%, similar to RF (27.6%) and significantly higher to ACPA (11.2%, p=0.003). The mean ±SD titer of anti-CarP was 890.5±794.9 IU/ml. Thirty-nine patients (25.6%) showed an US-detected erosive arthritis: all the patients referred at least one episode of clinical synovitis. Erosive arthritis was associated with anti-CarP (p=0.004) and ACPA (p=0.0008). A correlation between anti-CarP titer and US-erosive score was observed (r=0.2, p=0.01). Of note, anti-CarP were identified in 24.5% of double negative (ACPA-/RF-) patients, with erosive damage in 25% of them. Conclusions We identified a significant association between anti-CarP and US-detected erosive damage in SLE-related arthritis, in terms of frequency and severity. Our results suggest that anti-CarP could be considered as a candidate biomarker of severity in SLE patients with joint involvement.
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- 2018
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