531 results on '"Fabiola Atzeni"'
Search Results
2. Four-year real-world experience of secukinumab in a large Italian cohort of axial spondyloarthritis
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Roberta Ramonda, Mariagrazia Lorenzin, Maria Sole Chimenti, Salvatore D’Angelo, Antonio Marchesoni, Carlo Selmi, Ennio Lubrano, Leonardo Santo, Michele Maria Luchetti Gentiloni, Fabiola Atzeni, Alberto Cauli, Maria Manara, Maurizio Rossini, Roberta Foti, Giacomo Cozzi, Laura Scagnellato, Mario Ferraioli, Antonio Carriero, Nicoletta Luciano, Francesca Ruzzon, Mauro Fatica, Elena Fracassi, Andrea Doria, Rosario Foti, and Antonio Carletto
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axial spondyloarthritis ,r-axSpA/nr-axSpA biological therapy ,secukinumab (IL17i) ,IL17i effectiveness ,IL17i safety ,IL17i drug retention rate ,Immunologic diseases. Allergy ,RC581-607 - Abstract
ObjectivesThis study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA).MethodsConsecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded.ResultsWe enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex.ConclusionsSecukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.
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- 2024
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3. Retention rate of biologic and targeted synthetic anti-rheumatic drugs in elderly rheumatoid arthritis patients: data from GISEA registry
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Andreina Manfredi, Marco Fornaro, Chiara Bazzani, Simone Perniola, Alberto Cauli, Alessandra Rai, Ennio Giulio Favalli, Serena Bugatti, Maurizio Rossini, Rosario Foti, Fabrizio Conti, Giuseppe Lopalco, Anna Scalvini, Cristina Garufi, Mattia Congia, Roberto Gorla, Elisa Gremese, Fabiola Atzeni, Roberto Caporali, Florenzo Iannone, and Marco Sebastiani
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rheumatoid arthritis ,elderly ,comorbidities ,treatment ,retention rate ,safety ,Medicine (General) ,R5-920 - Abstract
ObjectivesAn increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old.MethodsRA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected.ResultsA total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p
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- 2024
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4. Management of psoriatic arthritis: a consensus opinion by expert rheumatologists
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Salvatore D’Angelo, Fabiola Atzeni, Maurizio Benucci, Gerolamo Bianchi, Fabrizio Cantini, Roberto Felice Caporali, Giorgio Carlino, Francesco Caso, Alberto Cauli, Francesco Ciccia, Maria Antonietta D’Agostino, Lorenzo Dagna, Christian Dejaco, Oscar Massimiliano Epis, Maria Grazia Ferrucci, Franco Franceschini, Enrico Fusaro, Marco Gabini, Roberto Gerli, Roberto Giacomelli, Marcello Govoni, Elisa Gremese, Giuliana Guggino, Annamaria Iagnocco, Florenzo Iannone, Bruno Laganà, Ennio Lubrano, Carlomaurizio Montecucco, Rosario Peluso, Roberta Ramonda, Maurizio Rossini, Carlo Salvarani, Gian Domenico Sebastiani, Marco Sebastiani, Carlo Selmi, Enrico Tirri, and Antonio Marchesoni
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psoriatic arthritis ,chronic inflammatory musculoskeletal disease ,comorbidities ,extra-articular manifestations ,diagnosis ,treatment ,Medicine (General) ,R5-920 - Abstract
BackgroundPsoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease involving several articular and extra-articular structures. Despite the important progresses recently made in all of the aspects of this disease, its management is still burdened by unresolved issues. The aim of this exercise was to provide a set of statements that may be helpful for the management of PsA.MethodsA group of 38 Italian rheumatologists with recognized expertise in PsA selected and addressed the following four topics: “early PsA,” “axial-PsA,” “extra-articular manifestations and comorbidities,” “therapeutic goals.” Relevant articles from the literature (2016–2022) were selected by the experts based on a PubMed search. A number of statements for each topic were elaborated.ResultsNinety-four articles were selected and evaluated, 68 out of the 1,114 yielded by the literature search and 26 added by the Authors. Each of the four topic was subdivided in themes as follows: transition from psoriasis to PsA, imaging vs. CASPAR criteria in early diagnosis, early treatment for “early PsA”; axial-PsA vs. axialspondyloarthritis, diagnosis, clinical evaluation, treatment, standard radiography vs. magnetic resonance imaging for “axial PsA”; influence of inflammatory bowel disease on the therapeutic choice, cardiovascular comorbidity, bone damage, risk of infection for “comorbidities and extra-articular manifestations”; target and tools, treat-to-target strategy, role of imaging for “therapeutic goals.” The final document consisted of 49 statements.DiscussionThe final product of this exercise is a set of statements concerning the main issues of PsA management offering an expert opinion for some unmet needs of this complex disease.
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- 2023
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5. Derivation and validation of four patient clusters in Still’s disease, results from GIRRCS AOSD-study group and AIDA Network Still Disease Registry
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Marcello Govoni, Annamaria Iagnocco, Carlomaurizio Montecucco, Sara Monti, Eduardo Martin-Nares, Paola Cipriani, Piero Ruscitti, Roberto Giacomelli, Luca Cantarini, Giuseppe Lopalco, Lorenzo Dagna, Francesco Carubbi, Antonio Vitale, Fatma Alibaz-Öner, Haner Direskeneli, Petros P Sfikakis, Giacomo Emmi, Claudia Fabiani, Gabriele Simonini, Daniele Mauro, Giuliana Guggino, Francesco Ciccia, Elena Bartoloni, Fabiola Atzeni, Daniela Iacono, Ilenia Pantano, Luisa Costa, Francesco Caso, Bruno Frediani, Benson Ogunjimi, Serena Bugatti, Ludovico De Stefano, Onorina Berardicurti, Ilenia Di Cola, Silvia Rossi, Abdurrahman Tufan, José Hernández-Rodríguez, Lampros Fotis, Antonio Gidaro, Jiram Torres-Ruiz, Paolo Sfriso, Luca Navarini, Francesco La Torre, Marco Valenti, Francesco Masedu, Samar Tharwat, Andrea Hinojosa-Azaola, Alberto Lo Gullo, Valeria Caggiano, Claudia Di Muzio, Marcella Prete, Federico Perosa, Henrique Giardini, Isabele Parente de Brito Antonelli, Ibrahim A Almaghlouth, Kazi Asfina, Gizem Sevik, Gafaar Ragab, Maria Cristina Maggio, Joanna Makowska, Emanuela Del Giudice, Armin Maier, and Sukran Erten
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Medicine - Abstract
Background Different patient clusters were preliminarily suggested to dissect the clinical heterogeneity in Still’s disease. Thus, we aimed at deriving and validating disease clusters in a multicentre, observational, prospective study to stratify these patients.Methods Patients included in GIRRCS AOSD-study group and AIDA Network Still Disease Registry were assessed if variables for cluster analysis were available (age, systemic score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and ferritin). K-means algorithm with Euclidean metric and Elbow plot were used to derive an adequate number of clusters.Results K-means clustering assessment provided four clusters based on means standardised according to z-scores on 349 patients. All clusters mainly presented fever, skin rash and joint involvement. Cluster 1 was composed by 115 patients distinguished by lower values of age and characterised by skin rash myalgia, sore throat and splenomegaly. Cluster 2 included 128 patients identified by lower levels of ESR, ferritin and systemic score; multiorgan manifestations were less frequently observed. Cluster 3 comprised 31 patients categorised by higher levels of CRP and ferritin, they were characterised by fever and joint involvement. Cluster 4 contained 75 patients derived by higher values of age and systemic score. Myalgia, sore throat, liver involvement and life-threatening complications, leading to a high mortality rate, were observed in these patients.Conclusions Four patient clusters in Still’s disease may be recognised by a multidimensional characterisation (‘Juvenile/Transitional’, ‘Uncomplicated’, ‘Hyperferritinemic’ and ‘Catastrophic’). Of interest, cluster 4 was burdened by an increased rate of life-threatening complications and mortality, suggesting a more severe patient group.
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- 2023
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6. Mortality risk factors in primary Sjögren syndrome: a real-world, retrospective, cohort studyResearch in context
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Pilar Brito-Zerón, Alejandra Flores-Chávez, Ildiko Fanny Horváth, Astrid Rasmussen, Xiaomei Li, Peter Olsson, Arjan Vissink, Roberta Priori, Berkan Armagan, Gabriela Hernandez-Molina, Sonja Praprotnik, Luca Quartuccio, Nevsun Inanç, Burcugül Özkızıltaş, Elena Bartoloni, Agata Sebastian, Vasco C. Romão, Roser Solans, Sandra G. Pasoto, Maureen Rischmueller, Carlos Galisteo, Yasunori Suzuki, Virginia Fernandes Moça Trevisani, Cecilia Fugmann, Andrés González-García, Francesco Carubbi, Ciprian Jurcut, Toshimasa Shimizu, Soledad Retamozo, Fabiola Atzeni, Benedikt Hofauer, Sheila Melchor-Díaz, Tamer Gheita, Miguel López-Dupla, Eva Fonseca-Aizpuru, Roberto Giacomelli, Marcos Vázquez, Sandra Consani, Miriam Akasbi, Hideki Nakamura, Antónia Szántó, A. Darise Farris, Li Wang, Thomas Mandl, Angelica Gattamelata, Levent Kilic, Katja Perdan Pirkmajer, Kerem Abacar, Abdurrahman Tufan, Salvatore de Vita, Hendrika Bootsma, Manuel Ramos-Casals, S. Arends, E. Treppo, S. Longhino, V. Manfrè, M. Rizzo, C. Baldini, S. Bombardieri, M. Bandeira, M. Silvéiro-António, R. Seror, X. Mariette, G. Nordmark, D. Danda, P. Wiland, R. Gerli, S.K. Kwok, S.H. Park, M. Kvarnstrom, M. Wahren-Herlenius, S. Downie-Doyle, D. Sene, D. Isenberg, V. Valim, V. Devauchelle-Pensec, A. Saraux, J. Morel, C. Morcillo, P.E. Díaz Cuiza, B.E. Herrera, L. González-de-Paz, and A. Sisó-Almirall
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Sjögren syndrome ,Mortality ,Systemic disease ,Lymphoma ,Cardiovascular ,Infection ,Medicine (General) ,R5-920 - Abstract
Summary: Background: What baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score. Methods: In this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables. Findings: Between January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death. Interpretation: The key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS. Funding: Novartis.
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- 2023
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7. Fibrosing Progressive Interstitial Lung Disease in Rheumatoid Arthritis: A Multicentre Italian Study
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Marco Sebastiani, Vincenzo Venerito, Elenia Laurino, Stefano Gentileschi, Fabiola Atzeni, Claudia Canofari, Dario Andrisani, Giulia Cassone, Marlea Lavista, Francesco D’Alessandro, Caterina Vacchi, Arnaldo Scardapane, Bruno Frediani, Massimiliano Cazzato, Carlo Salvarani, Florenzo Iannone, and Andreina Manfredi
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rheumatoid arthritis ,interstitial lung disease (ILD) ,progressive fibrosing ILD ,high-resolution computed tomography ,nintedanib ,Medicine - Abstract
Background: The INBUILD study demonstrated the efficacy of nintedanib in the treatment of progressive fibrosing interstitial lung disease different to idiopathic pulmonary fibrosis, including rheumatoid arthritis (RA)-related ILD. Nevertheless, the prevalence of RA-ILD patients that may potentially benefit from nintedanib remains unknown. Objectives and methods: The aim of the present multicentre study was to investigate the prevalence and possible associated factors of fibrosing progressive patterns in a cross-sectional cohort of RA-ILD patients. Results: One hundred and thirty-four RA-ILD patients with a diagnosis of RA-ILD, who were confirmed at high-resolution computed tomography and with a follow-up of at least 24 months, were enrolled. The patients were defined as having a progressive fibrosing ILD in case of a relative decline in forced vital capacity > 10% predicted and/or an increased extent of fibrotic changes on chest imaging in a 24-month period. Respiratory symptoms were excluded to reduce possible bias due to the retrospective interpretation of cough and dyspnea. According to radiologic features, ILD was classified as usual interstitial pneumonia (UIP) in 50.7% of patients, nonspecific interstitial pneumonia in 19.4%, and other patterns in 29.8%. Globally, a fibrosing progressive pattern was recorded in 36.6% of patients (48.5% of patients with a fibrosing pattern) with a significant association to the UIP pattern. Conclusion: We observed that more than a third of RA-ILD patients showed a fibrosing progressive pattern and might benefit from antifibrotic treatment. This study shows some limitations, such as the retrospective design. The exclusion of respiratory symptoms’ evaluation might underestimate the prevalence of progressive lung disease but increases the value of results.
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- 2023
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8. Osteoimmunology of Spondyloarthritis
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Angelo Fassio, Fabiola Atzeni, Maurizio Rossini, Valeria D’Amico, Francesco Cantatore, Maria Sole Chimenti, Chiara Crotti, Bruno Frediani, Andrea Giusti, Giusy Peluso, Guido Rovera, Palma Scolieri, Vincenzo Raimondo, Davide Gatti, and on behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology
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osteoimmunology ,spondyloarthritis ,pathophysiology ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The mechanisms underlying the development of bone damage in the context of spondyloarthritis (SpA) are not completely understood. To date, a considerable amount of evidence indicates that several developmental pathways are crucially involved in osteoimmunology. The present review explores the biological mechanisms underlying the relationship between inflammatory dysregulation, structural progression, and osteoporosis in this diverse family of conditions. We summarize the current knowledge of bone biology and balance and the foundations of bone regulation, including bone morphogenetic protein, the Wnt pathway, and Hedgehog signaling, as well as the role of cytokines in the development of bone damage in SpA. Other areas surveyed include the pathobiology of bone damage and systemic bone loss (osteoporosis) in SpA and the effects of pharmacological treatment on focal bone damage. Lastly, we present data relative to a survey of bone metabolic assessment in SpA from Italian bone specialist rheumatology centers. The results confirm that most of the attention to bone health is given to postmenopausal subjects and that the aspect of metabolic bone health may still be underrepresented. In our opinion, it may be the time for a call to action to increase the interest in and focus on the diagnosis and management of SpA.
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- 2023
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9. The Role of Alarmins in Osteoarthritis Pathogenesis: HMGB1, S100B and IL-33
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Antonino Palumbo, Fabiola Atzeni, Giuseppe Murdaca, and Sebastiano Gangemi
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osteoarthritis ,alarmins ,DAMPs ,cytokines ,HMGB1 ,S100B ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the largest disability problem worldwide. Recent findings have described the role of damage-associated molecular patterns (DAMPs) in the course of the disease. In particular, alarmins such as HMGB1, IL-33, and S100B, appear implicated in enhancing articular inflammation and favouring a catabolic switch in OA chondrocytes. The aims of this review are to clarify the molecular signalling of these three molecules in OA pathogenesis, to identify their possible use as staging biomarkers, and, most importantly, to find out whether they could be possible therapeutic targets. Osteoarthritic cartilage expresses increased levels of all three alarmins. HMGB1, in particular, is the most studied alarmin with increased levels in cartilage, synovium, and synovial fluid of OA patients. High levels of HMGB1 in synovial fluid of OA joints are positively correlated with radiological and clinical severity. Counteracting HMGB1 strategies have revealed improving results in articular cells from OA patients and in OA animal models. Therefore, drugs against this alarmin, such as anti-HMGB1 antibodies, could be new treatment possibilities that can modify the disease course since available medications only alleviate symptoms.
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- 2023
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10. Metabolic Syndrome and Its Components Have a Different Presentation and Impact as Cardiovascular Risk Factors in Psoriatic and Rheumatoid Arthritis
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Fabiola Atzeni, Laura La Corte, Mariateresa Cirillo, Manuela Giallanza, James Galloway, and Javier Rodríguez-Carrio
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metabolic syndrome ,arthritis ,psoriatic ,rheumatoid ,heart disease risk factors ,Medicine - Abstract
Patients with chronic inflammatory arthritis have a higher cardiovascular (CV) risk than the general population. Traditional CV risk factors are clearly implicated, while the impact of metabolic syndrome (MetS) is less defined. The aim of this study was to compare MetS prevalence and impact on the CV risk in psoriatic arthritis (PsA) versus rheumatoid arthritis (RA). A retrospective analysis of real-world data of PsA and RA patients referred to a rheumatology clinic was conducted. The following data were extracted and compared: demographic data; clinical data; presence of traditional CV risk factors and MetS. Univariate and multivariate models were used to compare the impact of MetS and its components in patients with PsA versus RA. Overall, 170 patients were included (PsA: 78; RA; 92). The two groups differed significantly in mean age, disease duration, and presence of MetS, while other variables were comparable. Univariate and multivariate analysis identified distinct predictors of MetS in PsA (hypertension) and RA (dyslipidemia). The history of CV events was similar in the two groups. Predictors of CV events were MetS and most of its components in PsA, while dyslipidemia was the strongest predictor in RA. These associations were stronger in PsA than in RA. In conclusion, the impact of MetS and its components is different in PsA and RA. The association of these risk factors with CV events is stronger in PsA than in RA. This suggests the implication of different mechanisms, which may require distinct strategies for the prevention of CV events in PsA and RA.
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- 2023
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11. Evidence for a genetic contribution to the ossification of spinal ligaments in Ossification of Posterior Longitudinal Ligament and Diffuse idiopathic skeletal hyperostosis: A narrative review
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Ana Rita Couto, Bruna Parreira, Deborah M. Power, Luís Pinheiro, João Madruga Dias, Irina Novofastovski, Iris Eshed, Piercarlo Sarzi-Puttini, Nicola Pappone, Fabiola Atzeni, Jorrit-Jan Verlaan, Jonneke Kuperus, Amir Bieber, Pasquale Ambrosino, David Kiefer, Muhammad Asim Khan, Reuven Mader, Xenofon Baraliakos, and Jácome Bruges-Armas
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ossification ,genetics ,ectopic calcification ,diffuse idiopathic skeletal hyperostosis ,ossification of posterior longitudinal ligament ,Genetics ,QH426-470 - Abstract
Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ossification of the Posterior Longitudinal Ligament (OPLL) are common disorders characterized by the ossification of spinal ligaments. The cause for this ossification is currently unknown but a genetic contribution has been hypothesized. Over the last decade, many studies on the genetics of ectopic calcification disorders have been performed, mainly on OPLL. Most of these studies were based on linkage analysis and case control association studies. Animal models have provided some clues but so far, the involvement of the identified genes has not been confirmed in human cases. In the last few years, many common variants in several genes have been associated with OPLL. However, these associations have not been at definitive levels of significance and evidence of functional significance is generally modest. The current evidence suggests a multifactorial aetiopathogenesis for DISH and OPLL with a subset of cases showing a stronger genetic component.
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- 2022
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12. Rheumatoid Arthritis from Easy to Complex Disease: From the '2022 GISEA International Symposium'
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Simone Perniola, Maria Sole Chimenti, Francesca Romana Spinelli, Bruno Frediani, Rosario Foti, Sara Ferrigno, Cristina Garufi, Giulia Cassone, Vincenzo Venerito, Fabiola Atzeni, Roberto Caporali, Fabrizio Conti, Ennio Giulio Favalli, Florenzo Iannone, Marco Sebastiani, Gian Franco Ferraccioli, Giovanni Lapadula, and Elisa Gremese
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rheumatoid arthritis ,seronegative ,seropositive ,remission ,therapy ,Medicine - Abstract
Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium.
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- 2023
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13. Cardiovascular Risk in Systemic Inflammatory Arthritis
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Fabiola Atzeni and Alessandra Alciati
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n/a ,Medicine - Abstract
In recent years, several papers have been published on cardiovascular (CV) involvement, risk, management, and treatment in systemic inflammatory arthritis (SIA), including rheumatoid arthritis, (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) [...]
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- 2023
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14. Cardiovascular Involvement in Sjögren’s Syndrome
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Fabiola Atzeni, Francesco Gozza, Giacomo Cafaro, Carlo Perricone, and Elena Bartoloni
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risk factors ,drugs ,heart ,Sjögren’s syndrome ,cardiovascular risk ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Sjögren Syndrome (SS) seems to be associated with a greater “overall risk” of cardiovascular (CV) and cerebrovascular events. Although not conventionally considered a feature of the disease, CV events represent a major burden in SS patients. CV risk is the consequence of a complex combination of multiple factors, including traditional risk factors and disease-related mechanisms. A complex relationships between disease-related features, endothelial dysfunction and traditional risk factor has been suggested. Several drugs are available for treating the systemic manifestations of SS, however they have shown positive effects on different outcomes of the disease, but until today the data on the role of these drugs on CV events are scarse. Given these data, the aim of this review was to evaluate the risk of CV risk in primary SS and the effect of the drugs on this manifestation.
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- 2022
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15. Early Spondyloarthritis Clinic: Organizational Improvements in the Patient Journey
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Salvatore D'Angelo, Antonella Afeltra, Fabiola Atzeni, Elena Baldissera, Maurizio Caminiti, Francesco Ciccia, Maria Antonietta D'Agostino, Lorenzo Dagna, Gian Luca Erre, Franco Franceschini, Enrico Fusaro, Roberto Giacomelli, Elisa Gremese, Giuliana Guggino, Claudia Lomater, Ennio Lubrano, Angela Anna Padula, Giuseppa Pagano Mariano, Romualdo Russo, Piercarlo Sarzi Puttini, Raffaele Scarpa, Carlo Selmi, Enrico Tirri, Stefano Ferri, and Florenzo Iannone
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spondyloarthritis ,Early SpA Clinic ,rheumatology ,patient journey ,early diagnosis ,hospital management ,Medicine (General) ,R5-920 - Abstract
Spondyloarthritis are chronic inflammatory diseases affecting spine, peripheral joints and enthesis, as well as extra-articular sites (bowel, eyes, skin). Diagnosis of spondyloarthritis often is slow and requires a multidisciplinary approach. The “Early SpA Clinic” project aimed at improving the patient care and journeys, by solving some organizational issues existing in Rheumatology Clinics. The “Early SpA Clinic” involved 19 Italian Rheumatology Centers using in-depth organizational analyses to identify areas for improvement. From the results of the analyses, some organizational solutions were suggested, and their impact measured at the end of the project through specific KPI. With the implementation of the suggested organizational solutions, Centers achieved relevant results, positively impacting on all the phases of the patient journey: decrease in waiting lists (−23%) and in the time length to transit the Center (−22%), increase in the percentage of new diagnoses (+20%), in the saturation of outpatient clinic capacity (+16%), and in the patient satisfaction (+4%). Centers involved in the “Early SpA Clinic” implemented several organizational actions based on an overall assessment of their activities and on solutions that required no additional resources. Overall, the Centers achieved the “Early SpA Clinic” objectives in terms of better management of resources, personnel, spaces, equipment, in relation to the volumes of patients.
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- 2022
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16. Antifibrotic drugs in connective tissue disease-related interstitial lung disease (CTD-ILD): from mechanistic insights to therapeutic applications
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Gian Luca Erre, Marco Sebastiani, Andreina Manfredi, Elisabetta Gerratana, Fabiola Atzeni, Giuseppe Passiu, and Arduino A Mangoni
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connective tissue diseases ,idiopathic inflammatory myopathies ,interstitial lung disease ,pirfenidone ,nintedanib ,rheumatoid arthritis ,sjögren’s syndrome ,systemic sclerosis ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Fibrosing interstitial lung disease (ILD) is one of the most important causes of morbidity and mortality in patients with connective tissue diseases (CTDs), which include systemic sclerosis, rheumatoid arthritis, Sjögren’s syndrome, idiopathic inflammatory myositis and systemic lupus erythematosus. The treatment of CTD-ILDs is challenging due to the paucity of proven effective treatments. Recently, two antifibrotic drugs conditionally approved for use in patients with idiopathic pulmonary fibrosis, nintedanib and pirfenidone, have been trialled in CTD-ILDs based on overlapping pathological and clinical features between the two diseases. In this narrative review, we discuss the experimental evidence and clinical trials investigating the efficacy and safety of antifibrotic drugs in patients with CTD-ILDs and the potential mechanisms of action involved. Results from clinical trials suggest that nintedanib use retards lung function decline in progressive fibrotic CTD-ILDs. By contrast, the evidence for the efficacy of pirfenidone in these groups is not equally compelling. Further, well-designed randomized clinical trials are needed to evaluate the efficacy and safety of individual antifibrotic drugs in specific CTD-ILD subgroups.
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- 2021
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17. Clinical Features of Diabetes Mellitus on Rheumatoid Arthritis: Data from the Cardiovascular Obesity and Rheumatic DISease (CORDIS) Study Group
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Fabio Cacciapaglia, Francesca Romana Spinelli, Elena Bartoloni, Serena Bugatti, Gian Luca Erre, Marco Fornaro, Andreina Manfredi, Matteo Piga, Garifallia Sakellariou, Ombretta Viapiana, Fabiola Atzeni, and Elisa Gremese
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diabetes mellitus ,rheumatoid arthritis ,biological drugs ,Medicine - Abstract
Rheumatoid arthritis (RA) and diabetes mellitus (DM) are linked by underlying inflammation influencing their development and progression. Nevertheless, the profile of diabetic RA patients and the impact of DM on RA need to be elucidated. This cross-sectional study includes 1523 patients with RA and no episodes of cardiovascular events, followed up in 10 Italian University Rheumatologic Centers between 1 January and 31 December 2019 belonging to the “Cardiovascular Obesity and Rheumatic DISease (CORDIS)” Study Group of the Italian Society of Rheumatology. The demographic and clinical features of DM RA patients were compared to non-diabetic ones evaluating factors associated with increased risk of DM. Overall, 9.3% of the RA patients had DM, and DM type 2 was more common (90.2%). DM patients were significantly older (p < 0.001), more frequently male (p = 0.017), with a significantly higher BMI and mean weight (p < 0.001) compared to non-diabetic patients. DM patients were less likely to be on glucocorticoids (p < 0.001), with a trend towards a more frequent use of b/ts DMARDs (p = 0.08), and demonstrated higher HAQ (p = 0.001). In around 42% of patients (n = 114), DM diagnosis preceded that of RA. Treatment lines were identical in diabetic and non-diabetic RA patients. DM is a comorbidity that may influence RA management and outcome. The association between DM and RA supports the theory of systemic inflammation as a condition underlying the development of both diseases. DM may not have a substantial impact on bDMARDs resistance, although further investigation is required to clarify the implications of biological therapy resistance in RA patients.
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- 2023
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18. Evolution of Rheumatoid-Arthritis-Associated Interstitial Lung Disease in Patients Treated with JAK Inhibitors: A Retrospective Exploratory Study
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Vincenzo Venerito, Andreina Manfredi, Antonio Carletto, Stefano Gentileschi, Fabiola Atzeni, Serena Guiducci, Marlea Lavista, Laura La Corte, Elisa Pedrollo, Arnaldo Scardapane, Caterina Tomassini, Bruno Frediani, Carlo Salvarani, Florenzo Iannone, and Marco Sebastiani
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rheumatoid arthritis ,interstitial lung disease ,JAK inhibitors ,Medicine - Abstract
Background: The aim of this multicenter retrospective study was to investigate the effectiveness and safety of the available JAK-inhibitors (JAKi) in patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD). Methods: We retrospectively analyzed patients with classified RA and RA-ILD undergoing JAKi in 6 Italian tertiary centers from April 2018 to June 2022. We included patients with at least 6 months of active therapy and one high-resolution chest tomography (HRCT) carried out within 3 months of the start of JAKi treatment. The HRCT was then compared to the most recent one carried out within 3 months before the last available follow-up appointment. We also kept track of the pulmonary function tests. Results: We included 43 patients with RA-ILD and 23 males (53.48%) with a median age (interquartile range, IQR) of 68.87 (61.46–75.78) treated with JAKi. The median follow-up was 19.1 months (11.03–34.43). The forced vital capacity remained stable in 22/28 (78.57%) patients, improved in 3/28 (10.71%) and worsened in 3/28 (10.71%). The diffusing capacity of lung for carbon monoxide showed a similar trend, remaining stable in 18/25 (72%) patients, improving in 2/25 (8%) and worsening in 5/25 (20%). The HRCT remained stable in 37/43 (86.05) cases, worsened in 4/43 (9.30%) and improved in the last 2 (4.65%). Discussion: This study suggests that JAKi therapy might be a safe therapeutic option for patients with RA-ILD in a short-term follow-up.
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- 2023
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19. From Bench to Bedside in Rheumatoid Arthritis from the '2022 GISEA International Symposium'
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Antonio Vitale, Stefano Alivernini, Roberto Caporali, Giulia Cassone, Dario Bruno, Luca Cantarini, Giuseppe Lopalco, Maurizio Rossini, Fabiola Atzeni, Ennio Giulio Favalli, Fabrizio Conti, Elisa Gremese, Florenzo Iannone, Gian Franco Ferraccioli, Giovanni Lapadula, and Marco Sebastiani
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inflammatory arthropathies ,pathogenesis ,therapy ,inflammasome ,synovial tissue macrophage ,Medicine - Abstract
While precision medicine is still a challenge in rheumatic disease, in recent years many advances have been made regarding pathogenesis, the treatment of inflammatory arthropathies, and their interaction. New insight into the role of inflammasome and synovial tissue macrophage subsets as predictors of drug response give hope for future tailored therapeutic strategies and a personalized medicine approach in inflammatory arthropathies. Here, we discuss the main pathogenetic mechanisms and therapeutic approaches towards precision medicine in rheumatoid arthritis from the 2022 International GISEA/OEG Symposium.
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- 2023
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20. Parenchymal lung disease in adult onset Still’s disease: an emergent marker of disease severity—characterisation and predictive factors from Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort of patients
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Piero Ruscitti, Onorina Berardicurti, Daniela Iacono, Ilenia Pantano, Vasiliki Liakouli, Francesco Caso, Giacomo Emmi, Rosa Daniela Grembiale, Francesco Paolo Cantatore, Fabiola Atzeni, Federico Perosa, Raffaele Scarpa, Giuliana Guggino, Francesco Ciccia, Antonio Barile, Paola Cipriani, and Roberto Giacomelli
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Adult onset Still’s disease ,Lung disease ,Mortality ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Adult-onset Still’s disease (AOSD) is a systemic inflammatory disorder of unknown aetiology usually affecting young adults. Interestingly, recent evidence from the juvenile counterpart of AOSD suggested the emergent high fatality rate of lung disease (LD) in these patients. In this work, we aimed to characterise LD in AOSD, to identify associated clinical features and predictive factors, and to describe long-term outcomes of the disease comparing patients with LD and those without. Methods A retrospective assessment of prospectively followed patients, from January 2001 to December 2019, was provided to describe the rate of LD in AOSD, associated clinical features and predictive factors, and long-term outcomes. Patients with AOSD, who were included in Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort, were assessed. Results Out of 147 patients included in GIRRCS cohort, 18 (12.25%) patients were reported to be affected by LD, at the time of diagnosis of AOSD, who were characterised by older age, a higher prevalence of myalgia, of lymph node involvement, of pleuritis, and abdominal pain. Furthermore, patients with LD showed higher values of systemic score and ferritin. Among those clinical variables, older age and systemic score were also independently predictors of LD. Chest CT scans were also obtained, and the most common finding was the peripheral consolidations in 8 (44.4%) patients. Finally, a higher mortality rate, of 38.9%, was registered in patients with LD than others, since it was associated with a significant decreased survival rate. Conclusions The presence of LD could suggest an emergent cause of mortality in AOSD, as observed in juvenile counterpart recognising a further marker of severity and poor prognosis to be careful evaluated. Patients with LD were also characterised by some clinical features, higher values of systemic score and ferritin than the others, identifying a subset of patients mostly burdened by systemic signs and symptoms. Although specific designed future studies are needed to fully elucidate the significance of LD in AOSD, a more accurate evaluation and management of this feature could improve the long-term outcomes of these patients.
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- 2020
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21. Retroviruses in the pathogenesis of systemic lupus erythematosus: Are they potential therapeutic targets?
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Rossella Talotta, Fabiola Atzeni, and Magdalena Janina Laska
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systemic lupus erythematosus ,retroviruses ,human immunodeficiency virus ,human endogenous retroviruses ,antiretroviral therapy ,Internal medicine ,RC31-1245 - Abstract
The pathogenesis of systemic lupus erythematosus (SLE) is characterised by the hyper-activation of immunologic pathways related to the antiviral response. Exogenous and endogenous retroviruses, by integrating their DNA templates in the host cell genome, may epigenetically control the transcription of genes involved in the immune response. Furthermore, their nucleic acids or neo-synthesized proteins could stimulate the sensor molecules placed upstream the inflammatory cascade. Exogenous retroviruses, like human immunodeficiency virus, have been associated to SLE-like manifestations or to a fair SLE diagnosis. In addition, there is some evidence confirming a pathogenic role of human endogenous retroviruses in SLE. In line with these data, the use of antiretroviral agents could represent an attractive opportunity in the future therapeutic algorithms of this disease, but studies are still missing.
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- 2020
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22. Axial Spondyloarthritis: Reshape the Future—From the '2022 GISEA International Symposium'
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Fausto Salaffi, Cesare Siragusano, Alessandra Alciati, Giulia Cassone, Salvatore D’Angelo, Serena Guiducci, Ennio Giulio Favalli, Fabrizio Conti, Elisa Gremese, Florenzo Iannone, Roberto Caporali, Marco Sebastiani, Gian Franco Ferraccioli, Giovanni Lapadula, and Fabiola Atzeni
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axial spondyloarthritis ,pain ,pathogenesis ,therapy ,Medicine - Abstract
The term “axial spondyloarthritis” (axSpA) refers to a group of chronic rheumatic diseases that predominantly involve the axial skeleton and consist of ankylosing spondylitis, reactive arthritis, arthritis/spondylitis associated with psoriasis (PsA) and arthritis/spondylitis associated with inflammatory bowel diseases (IBD). Moreover, pain is an important and common symptom of axSpA. It may progress to chronic pain, a more complicated bio-psychosocial phenomena, leading to a significant worsening of quality of life. The development of the axSpA inflammatory process is grounded in the complex interaction between genetic (such as HLA B27), epigenetic, and environmental factors associated with a dysregulated immune response. Considering the pivotal contribution of IL-23 and IL-17 in axSpA inflammation, the inhibition of these cytokines has been evaluated as a potential therapeutic strategy. With this context, here we discuss the main pathogenetic mechanisms, therapeutic approaches and the role of pain in axSpA from the 2022 International GISEA/OEG Symposium.
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- 2022
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23. Arthritis in Systemic Lupus Erythematosus: From 2022 International GISEA/OEG Symposium
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Fulvia Ceccarelli, Marcello Govoni, Matteo Piga, Giulia Cassone, Francesco Paolo Cantatore, Giulio Olivieri, Alberto Cauli, Ennio Giulio Favalli, Fabiola Atzeni, Elisa Gremese, Florenzo Iannone, Roberto Caporali, Marco Sebastiani, Gian Franco Ferraccioli, Giovanni Lapadula, and Fabrizio Conti
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systemic lupus erythematosus ,arthritis ,Jaccoud’s arthropathy ,rhupus ,therapy ,Medicine - Abstract
Musculoskeletal involvement is one of the most common manifestations of systemic lupus erythematosus (SLE), with a negative impact on both quality of life and overall prognosis. SLE arthritis can be classified into three different subtypes, with different prevalence and characteristic biomarkers and MRI findings. Identifying the pathogenetic mechanisms underlying musculoskeletal manifestations’ development is crucial to develop therapeutic strategies to suppress synovial inflammation, prevent erosions and deformities, and improve SLE patients’ quality of life. Hence, here we discuss the main pathogenetic mechanisms and therapeutic approaches of musculoskeletal manifestations of SLE from the 2022 International GISEA/OEG Symposium.
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- 2022
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24. Psoriatic Arthritis and Metabolic Syndrome: Is There a Role for Disease Modifying Anti-Rheumatic Drugs?
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Fabiola Atzeni, Elisabetta Gerratana, Ignazio Francesco Masala, Sara Bongiovanni, Piercarlo Sarzi-Puttini, and Javier Rodríguez-Carrio
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metabolic syndrome ,psoriatic arthritis ,dyslipidemia ,diabetes ,hypertension ,Medicine (General) ,R5-920 - Abstract
Although psoriatic arthritis (PsA) primarily leads to joint and skin damage, it is associated with higher prevalence of metabolic syndrome (MetS) and its components, namely hypertension, dyslipidemia, obesity, and type II diabetes. Additionally, chronic inflammation is known to aggravate these cardiometabolic factors, thus explaining the enhanced cardiovascular (CV) morbidity and mortality in RA. Furthermore, emerging evidence suggest that some risk factors can fuel inflammation, thus pointing to a bidirectional crosstalk between inflammation and cardiometabolic factors. Therefore, dampening inflammation by disease-modifying anti-rheumatic drugs (DMARDs) may be thought to ameliorate MetS burden and thus, CV risk and disease severity. In fact, recommendations for PsA management emphasize the need of considering comorbidities to guide the treatment decision process. However, the existing evidence on the impact of approved DMARDs in PsA on MetS and MetS components is far from being optimal, thus representing a major challenge for the clinical setting. Although a beneficial effect of some DMARDs such as methotrexate, TNF inhibitors and some small molecules is clear, no head-to-head studies are published and no evidence is available for other therapeutic approaches such as IL-23 or IL-17 inhibitors. This narrative review summarizes the main evidence related to the effect of DMARDs on MetS outcomes in PsA patients and identify the main limitations, research needs and future perspectives in this scenario.
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- 2021
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25. Subclinical and clinical atherosclerosis in rheumatoid arthritis: results from the 3-year, multicentre, prospective, observational GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) study
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Piero Ruscitti, Paola Cipriani, Vasiliki Liakouli, Daniela Iacono, Ilenia Pantano, Domenico Paolo Emanuele Margiotta, Luca Navarini, Giulia Maria Destro Castaniti, Nicola Maruotti, Gerardo Di Scala, Licia Picciariello, Francesco Caso, Sara Bongiovanni, Rosa Daniela Grembiale, Fabiola Atzeni, Raffaele Scarpa, Federico Perosa, Giacomo Emmi, Francesco Paolo Cantatore, Giuliana Guggino, Antonella Afeltra, Francesco Ciccia, and Roberto Giacomelli
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Rheumatoid arthritis ,Atherosclerosis ,Cardiovascular diseases ,Remission ,Type 2 diabetes ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Rheumatoid arthritis (RA) is associated with an increased risk of morbidity and mortality, when compared with general population, largely due to enhanced atherosclerotic disease. In this work, we aimed at assessing both occurrence and predictive factors of subclinical and clinical atherosclerosis in RA. Methods From January 1, 2015, to December 31, 2015, consecutive participants with RA, admitted to Italian Rheumatology Units, were assessed in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort. After that, those participants were followed up in a 3-year, prospective, observational study, assessing the occurrence of subclinical and clinical atherosclerosis and possible predictive factors. McNemar test was employed to assess the changes in subclinical and clinical atherosclerosis, and regression analyses exploited the ORs for the occurrence of those comorbidities. Results We analysed 841 participants, mostly female (82.2%) and with median age of 60 years (range 21–90). The remission was achieved and maintained by 41.8% of participants during the follow-up. We observed an increased rate of subclinical atherosclerosis at the end of follow-up (139 vs 203 participants, p
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- 2019
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26. AxSpA patients who also meet criteria for fibromyalgia: identifying distinct patient clusters using data from a UK national register (BSRBR-AS)
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Gary J. Macfarlane, Ejaz Pathan, Stefan Siebert, Jonathan Packham, Karl Gaffney, Ernest Choy, Raj Sengupta, Fabiola Atzeni, Kathryn R. Martin, Gareth T. Jones, and Linda E. Dean
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Axial spondyloarthritis ,Fibromyalgia ,Comorbidity ,Criteria ,Disease register ,Cluster analysis ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need. Identifying effective therapy is important but to what extent fibromyalgia-like symptoms relate to axSpA disease severity has not been established. The aim of the current analysis was to determine whether distinct clusters of axSpA patients exist and if so to determine a) whether they differ in terms of prevalence of fibromyalgia and b) the features of patients in clusters with high prevalence. Methods The British Society for Rheumatology Biologics Register (BSRBR-AS) recruited axSpA patients from 83 centres 2012–2017. Clinical data, and information from patients was collected (including research criteria for fibromyalgia). Cluster analysis was undertaken using split samples for development and validation both in the whole population and the sub-group which met fibromyalgia criteria. Results One thousand three hundred thirty-eight participants were included of whom 23% met research criteria for fibromyalgia. Four clusters were identified. Two exhibited very high disease activity, one which was primarily axial (n = 347) and a smaller cluster (n = 32) with axial and peripheral disease, and in both groups more than half of members met criteria for fibromyalgia. The remaining two clusters (n = 437, n = 462) had overall less severe disease however the one which showed greater disease activity and poorer quality of life had a higher proportion meeting fibromyalgia criteria (16% v. 4%). Within those meeting fibromyalgia criteria there were three clusters. The two main groups were defined by level of symptom severity with a smaller third cluster noted to have high average swollen and tender joint counts and high levels of comorbidity. Conclusions The major feature defining clusters with a high proportion of persons meeting criteria for fibromyalgia is high axSpA disease activity although clusters with features of fibromyalgia in the absence of high disease activity also show moderately high prevalence. Management may be most successful with pharmacologic therapy to target inflammation but enhanced by the concurrent use of non-pharmacologic therapy in such patients.
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- 2019
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27. Is central sensitization an important determinant of functional disability in patients with chronic inflammatory arthritides?
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Giovanni Adami, Elisabetta Gerratana, Fabiola Atzeni, Camilla Benini, Elisabetta Vantaggiato, Denise Rotta, Luca Idolazzi, Maurizio Rossini, Davide Gatti, and Angelo Fassio
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Background: Central sensitization (CS) is a condition characterized by a disproportionate response to pain stimuli. We sought to investigate the prevalence of CS in patients with inflammatory arthritides and its association with measures of disease activity and functional disability. Methods: We conducted an observational retrospective study in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients. We administered to all the subjects in the study the CS inventory (CSI), a questionnaire that has been used for the diagnosis of CS. Demographic and clinical characteristics were collected as well as measures or disease activity [i.e. Simple Disease Activity Index, Disease Activity Score in PsA (DAPSA)] and functional disability [Health Assessment Questionnaire Disability Index (HAQ-DI)]. Patients with fibromyalgia were excluded from the analyses. The primary outcome measure was the presence of functional disability as assessed by HAQ-DI >1. Results: We enrolled 150 patients with inflammatory arthritides (78 PsA and 72 RA). Prevalence of CS was observed in 35.3% of the overall sample (29% in RA, 42.9% in PsA). Binary logistic regressions showed a strong, independent and linear association between functional disability and CS in both PsA and RA patients. The strength of this association was greater in PsA than in RA. Conclusion: CS is an important determinant of functional disability in patients with chronic inflammatory arthritides. PsA appeared to be more vulnerable to CS. In addition, in the presence of CS, DAPSA did not adequately capture the occurrence of functional disability. Therefore, special attention should be paid to PsA patients, in whom the concomitant diagnosis of CS should be routinely ruled out.
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- 2021
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28. Cross Cultural Adaptation and Validation of Italian Version of the Leeds Assessment of Neuropathic Symptoms and Signs Scale and Pain DETECT Questionnaire for the Distinction between Nociceptive and Neuropathic Pain
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Alberto Migliore, Gianfranco Gigliucci, Antimo Moretti, Alessio Pietrella, Marco Peresson, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Laura Bazzichi, Sara Liguori, and Giovanni Iolascon
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Medicine (General) ,R5-920 - Abstract
Objective. This study aimed to validate Italian versions of Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale and Pain DETECT questionnaire (PD-Q) and evaluate the ability of these questionnaires to discriminate between nociceptive and neuropathic pain. Design. Multicenter prospective validation cohort study. Subjects and Setting. One hundred patients were included with a diagnosis formulated by a specialist in outpatient settings (50 affected by knee osteoarthritis as nociceptive pain and 50 affected by trigeminal or postherpetic neuralgia as neuropathic pain). Methods. The Italian versions of both questionnaires according to Italian cultural characteristics were performed according to the following steps: (1) translation of the questionnaires from English into Italian; (2) review by a bilingual individual for consistency; (3) proposed version after a mail round between experts; (4) backward translation; (5) comparison with the original English version by the experts; (6) approved version of the questionnaires. One hundred patients were enrolled and completed the two questionnaires administered by a specialist or blinded nursing staff, at the baseline and after 24/48 hours. Internal consistency, stability, validity, and discriminative power were analyzed. Results. Statistically significant differences were reported about the ability of both questionnaires to discriminate between patients affected by neuropathic or nociceptive pain. Internal consistency for the Italian version of the LANSS was 0.76, and for PD-Q, it was 0.80, assessed by Cronbach’s α; LANSS showed a good test-retest reliability with an ICC of 0.76, and PD-Q showed a high test-retest reliability with an ICC of 0.96. For interrater reliability, there was a concordance rate of 83.3% between reference diagnosis and LANSS (Cohen’s kappa = 0.67, CI 95% 0.52–0.75). Conclusions. This study validated the Italian versions of LANSS and PD-Q as reliable instruments with good psychometric characteristics, for pain evaluation, discriminating between nociceptive and neuropathic pain. Our findings were similar to those observed in the original study. Furthermore, we have reported the test-retest reliability for both questionnaires, not addressed in original validation studies.
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- 2021
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29. Frequency of Renal Function Parameter Abnormalities in Patients with Psoriatic Arthritis and Rheumatoid Arthritis: Real-World Evidence from Clinical Practice
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Fabiola Atzeni, Pietro Muto, Javier Rodríguez-Carrio, and Ignazio Francesco Masala
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psoriatic arthritis ,rheumatoid arthritis ,kidney ,renal dysfunction ,remission ,Medicine - Abstract
Objective: Patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) commonly develop renal dysfunction due to either systemic inflammation or drug-related nephrotoxicity. This study compared renal function parameters in patients with PsA versus those with RA and examined the impact of clinical remission or disease relapse on renal function. Methods: This single-center retrospective study was conducted at the University Hospital of Messina, Italy. Adult patients (aged ≥18 years) with PsA or RA who attended the rheumatology clinic within the past 6 months were identified from electronic medical records. Results: In total, 45 patients with PsA (n = 23) or RA (n = 22) were included. The mean (standard deviation) age was 55.6 (15.9) years, and 78% of participants were female. Patient age, renal function, and medical history were generally similar between the two disease groups, although significantly more RA patients were smokers, and more PsA patients had comorbid hypertension. The prevalence of estimated glomerular filtration rate [eGFR] ≤90 mL/min/1.73 m2 at 1, 6, and 12 months of treatment ranged from 38.5% to 58.3% in the PsA group and from 45.5% to 54.5% in the RA group and did not significantly differ between disease groups. Clinical remission did not appear to affect renal function parameters in either disease group; however, relapse was associated with significantly higher serum creatinine levels in PsA patients at the same timepoint. Conclusion: In this study, patients with PsA and RA had a similar prevalence of renal function parameter abnormalities over 12 months of treatment. Disease relapse may impact renal function in patients with PsA.
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- 2022
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30. Imaging of diffuse idiopathic skeletal hyperostosis (DISH)
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Xenofon Baraliakos, Iris Eshed, Fabiola Atzeni, David Kiefer, Reuven Mader, Irina Novofastovski, Amir Bieber, Jorrit-Jan Jorrit-Jan Verlaan, and Nicola Pappone
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Medicine - Abstract
Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of ligaments and entheses. The condition usually affects the axial skeleton, in particular, at the thoracic segment, though also other portions of the spine are often involved. DISH often involves also peripheral tendinous and/or entheseal sites either alone, or in association with the involvement of peripheral joints. At times, new bone formation involves the bone itself, but sometimes it involves joints not usually affected by osteoarthritis (OA) which result in bony enlargement of the epiphysis, joints space narrowing and a reduced range of motion. Because of the entheseal involvement, DISH can be mistaken for seronegative spondyloarthropathies or for a 'simple' OA. Furthermore, other implications for the recognition of DISH include spinal fractures, difficult intubation and upper endoscopies, decreased response rates in DISH with concomitant spondyloarthritides, and increased likelihood to be affected by metabolic syndrome and cardiovascular diseases. This Atlas is intended to show the imaging finding in DISH in patients diagnosed with the condition by the Resnick classification criteria.
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- 2020
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31. Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still's disease. Analysis of the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.
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Paola Di Benedetto, Paola Cipriani, Daniela Iacono, Ilenia Pantano, Francesco Caso, Giacomo Emmi, Rosa Daniela Grembiale, Francesco Paolo Cantatore, Fabiola Atzeni, Federico Perosa, Raffaele Scarpa, Giuliana Guggino, Francesco Ciccia, Roberto Giacomelli, and Piero Ruscitti
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Medicine ,Science - Abstract
ObjectiveTo assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.MethodsThe predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiver-operating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively.ResultsIn assessed 147 patients with AOSD, levels of ferritin were predictive of MAS (OR: 1.971; P: 0.002; CI 95%: 1.280-3.035). The ROC curve showed that the best cut-off for ferritin was 1225 ng/ml in predicting MAS (sensitivity 88%; specificity 57%). Levels of CRP were predictive of mortality in these patients (OR: 2.155; P: 0.007; CI 95%: 1.228-3.783). The ROC curve showed that the best cut-off for CRP was 68.7 mg/L in predicting mortality (sensitivity 80%; specificity of 65%).ConclusionsWe reported the predictive role of ferritin and CRP on MAS and mortality, respectively, in a large cohort of patients with AOSD, identifying subsets at higher risk of poor prognosis. Considering that the analysis of CRP and ferritin is widely available, these results could be readily transferable into clinical practice, thus improving the management of patients with AOSD.
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- 2020
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32. Accelerated subcutaneous nodulosis in patients with rheumatoid arthritis treated with tocilizumab: a case series
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Rossella Talotta, Fabiola Atzeni, Alberto Batticciotto, Maria Chiara Ditto, Maria Chiara Gerardi, and Piercarlo Sarzi-Puttini
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Rheumatic nodulosis ,Tocilizumab ,Rheumatoid arthritis ,Medicine - Abstract
Abstract Background Tocilizumab is a monoclonal antibody directed against the interleukin-6 receptor, which is approved for the treatment of moderate-to-severe rheumatoid arthritis. Authors have found that it prevents lung and subcutaneous nodulosis in patients with rheumatoid arthritis but, to the best of our knowledge, there are no data concerning the acceleration of subcutaneous nodulosis during tocilizumab therapy. Case presentation We report for the first time a small case series of five patients with rheumatoid arthritis: a 46-year-old white woman, a 70-year-old white woman, a 63-year-old white woman, a 69-year-old white man, and a 72-year-old white woman (mean age 64 ± 10.6 years); they experienced worsening subcutaneous nodulosis during treatment with intravenously administered tocilizumab. Four of the five patients were positive for rheumatoid factor and five for anti-citrullinated peptide antibodies. All of the patients had previously been treated with various conventional and biological drugs; at the time of our observation, three were taking methotrexate, two hydroxychloroquine, and four were taking prednisone. Tocilizumab 8 mg/kg was administered intravenously every 4 weeks for a mean of 43.4 ± 32.4 months, and led to good disease control in three cases. All of the patients had a history of subcutaneous nodulosis, which considerably worsened during tocilizumab treatment, with the development of new nodules on their fingers, elbows, or in the inframammary fold, tending to ulcerate. The management of this medical event included discontinuation of methotrexate, the administration of steroids, the addition of hydroxychloroquine or colchicine, the use of antibiotics, and surgery. However, neither pharmacological nor surgical treatment was completely effective, as the nodules tended to recur and increased in number and size. Conclusions To the best of our knowledge, this is the first report describing accelerated subcutaneous nodulosis in a small case series of patients with rheumatoid arthritis treated with tocilizumab.
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- 2018
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33. Noninvasive imaging methods for evaluating cardiovascular involvement in patients with rheumatoid arthritis before and after anti-TNF drug treatment
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Fabiola Atzeni, Luigi Gianturco, Laura Boccassini, Piercarlo Sarzi-Puttini, Gianluca Bonitta, and Maurizio Turiel
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cardiovascular disease ,cardiovascular risk ,carotid ultrasound ,disease activity ,echocardiography ,myocardial alterations ,Medicine ,Medicine (General) ,R5-920 - Abstract
Aim: To use 2D speckle-tracking echocardiography, and conventional and tissue Doppler echocardiography to detect subclinical left ventricular myocardial dysfunction in patients with rheumatoid arthritis (RA). Methods: Thirty RA outpatients were assessed before and after 18 months of treatment with anti-TNF drugs, along with 30 healthy controls. Cardiovascular risk was assessed by means of ultrasound carotid assessment and comprehensive echocardiographic evaluation (conventional and speckle-tracking calculation). Results: The speckle-tracking analyses were significantly different between the two groups, with global longitudinal strain deformation in the apical four-chamber view being significantly lower in the RA patients (median: 18.78%, interquartile range [IQR]: 15.80–20.82% vs 20.16%, IQR: 19.03–21.89%; [p
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- 2019
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34. Microbial Agents as Putative Inducers of B Cell Lymphoma in Sjögren’s Syndrome through an Impaired Epigenetic Control: The State-of-The-Art
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Rossella Talotta, Piercarlo Sarzi-Puttini, and Fabiola Atzeni
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Introduction. Understanding the mechanisms underlying the pathogenesis of Sjögren’s syndrome (SS) is crucially important in order to be able to discriminate the steps that lead to B cell transformation and promptly identify the patients at risk of lymphomagenesis. The aim of this narrative review is to describe the evidence concerning the role that infections or dysbiosis plays in the epigenetic control of gene expression in SS patients and their possible involvement in B cell lymphomagenesis. Materials and Methods. We searched the PubMed and Google Scholar databases and selected a total of 92 articles published during the last 25 years that describe experimental and clinical studies of the potential associations of microbiota and epigenetic aberrations with the risk of B cell lymphoma in SS patients. Results and Discussion. The genetic background of SS patients is characterized by the hyperexpression of genes that are mainly involved in regulating the innate and adaptive immune responses and oncogenesis. In addition, salivary gland epithelial cells and lymphocytes both have an altered epigenetic background that enhances the activation of proinflammatory and survival pathways. Dysbiosis or chronic latent infections may tune the immune response and modify the cell epigenetic machinery in such a way as to give B lymphocytes an activated or transformed phenotype. It is also worth noting that transposable integrated retroelements may participate in the pathogenesis of SS and B cell lymphomagenesis by inducing DNA breaks, modulating cell gene expression, or generating aberrant transcripts that chronically stimulate the immune system. Conclusions. Microorganisms may epigenetically modify target cells and induce their transcriptome to generate an activated or transformed phenotype. The occurrence of lymphoma in more than 15% of SS patients may be the end result of a combination of genetics, epigenetics, and dysbiosis or latent infections.
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- 2019
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35. The Key Comorbidities in Patients with Rheumatoid Arthritis: A Narrative Review
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Peter C. Taylor, Fabiola Atzeni, Alejandro Balsa, Laure Gossec, Ulf Müller-Ladner, and Janet Pope
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rheumatoid arthritis ,comorbidities ,extra-articular manifestations ,tumour necrosis factor ,cardiovascular disease ,infections ,Medicine - Abstract
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should take into account these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This review summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.
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- 2021
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36. The Rheumatology Drugs for COVID-19 Management: Which and When?
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Fabiola Atzeni, Ignazio Francesco Masala, Javier Rodríguez-Carrio, Roberto Ríos-Garcés, Elisabetta Gerratana, Laura La Corte, Manuela Giallanza, Valeria Nucera, Agostino Riva, Gerard Espinosa, and Ricard Cervera
- Subjects
pneumonia ,COVID-19 ,SARS-CoV2 ,anti-IL-6 drugs ,HCQ ,Medicine - Abstract
Introduction: While waiting for the development of specific antiviral therapies and vaccines to effectively neutralize the SARS-CoV2, a relevant therapeutic strategy is to counteract the hyperinflammatory status, characterized by an increase mainly of interleukin (IL)-1β, IL-2, IL-6, IL-7, IL-8, and tumor necrosis factor (TNF)-α, which hallmarks the most severe clinical cases. ‘Repurposing’ immunomodulatory drugs and applying clinical management approved for rheumatic diseases represents a game-changer option. In this article, we will review the drugs that have indication in patients with COVID-19, including corticosteroids, antimalarials, anti-TNF, anti-IL-1, anti-IL-6, baricitinib, intravenous immunoglobulins, and colchicine. The PubMed, Medline, and Cochrane Library databases were searched for English-language papers concerning COVID-19 treatment published between January 2020 and October 2020. Results were summarized as a narrative review due to large heterogeneity among studies. In the absence of specific treatments, the use of immunomodulatory drugs could be advisable in severe COVID-19 patients, but clinical outcomes are still suboptimal. An early detection and treatment of the complications combined with a multidisciplinary approach could allow a better recovery of these patients.
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- 2021
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37. The Co-Morbidity between Bipolar and Panic Disorder in Fibromyalgia Syndrome
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Alessandra Alciati, Fabiola Atzeni, Daniela Caldirola, Giampaolo Perna, and Piercarlo Sarzi-Puttini
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bipolar disorders ,panic disorder ,fibromyalgia ,co-morbidity ,Medicine - Abstract
About half of the patients with fibromyalgia (FM) had a lifetime major depression episode and one third had a panic disorder (PD). Because the co-morbidity between bipolar disorder (BD) and PD marks a specific subtype of BD we aimed to investigate if co-morbid BD/PD (comBD/PD) occurs more frequently than the single disorder in FM patients and evaluate the clinical significance and timing of this co-morbidity. Further, we explored the role of co-morbid subthreshold BD and PD. In 118 patients with FM, lifetime threshold and sub-threshold mood disorders and PD were diagnosed with Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) Clinical Interview. Demographic and clinical variables were compared in co-morbid BD/PD (comBD/PD) and not co-morbid BD/PD (nocomBD/PD) subgroups. The co-morbidity BD/PD was seen in 46.6% of FM patients and in 68.6% when patients with minor bipolar (MinBD) and sub-threshold panic were included. These rates are higher than those of the general population and BD outpatients. There were no statistically significant differences between threshold and sub-threshold comBD/PD and nocom-BD/PD subgroups in demographic and clinical parameters. In the majority of patients (78.2%), the onset of comBD/PD preceded or was contemporary with FM. These findings support the hypothesis that comBD/PD is related to the development of FM in a subgroup of patients.
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- 2020
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38. Safety Profile of Biologics Used in Rheumatology: An Italian Prospective Pharmacovigilance Study
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Maria Antonietta Barbieri, Giuseppe Cicala, Paola Maria Cutroneo, Elisabetta Gerratana, Caterina Palleria, Caterina De Sarro, Ada Vero, Luigi Iannone, Antonia Manti, Emilio Russo, Giovambattista De Sarro, Fabiola Atzeni, and Edoardo Spina
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pharmacovigilance ,biologic drugs ,inflammatory arthritis ,adverse events ,real-world data ,treatment failure ,Medicine - Abstract
Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.
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- 2020
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39. Safety of Abatacept in Italian Patients with Rheumatoid Arthritis and Interstitial Lung Disease: A Multicenter Retrospective Study
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Giulia Cassone, Andreina Manfredi, Fabiola Atzeni, Vincenzo Venerito, Caterina Vacchi, Valentina Picerno, Federica Furini, Gian Luca Erre, Paola Tomietto, Anna Laura Fedele, Giovanni Della Casa, Valeria Nucera, Chiara Giannitti, Carlo Salvarani, and Marco Sebastiani
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rheumatoid arthritis ,interstitial lung disease ,safety ,therapy ,abatacept ,Medicine - Abstract
Background: Treatment of rheumatoid arthritis (RA)-related interstitial lung disease (ILD) is challenging, and many conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) have been associated with ILD development or progression. The aim of this multicentric retrospective study was to analyze the evolution of ILD in Italian RA-ILD patients treated with abatacept (ABA). Methods: All RA-ILD patients treated with ABA for at least six months were retrospectively evaluated. Serology, previous and concurrent therapies, chest high-resolution computer tomography (HRCT), forced vital capacity (FVC), and lung diffusion of carbon monoxide (CO, DLCO) were collected. Results: Forty-four patients were included; HRCT, FVC, and DLCO were analyzed at baseline, at one year, and at the end of follow-up. A remission or a low disease activity of RA was reached in 41/44 patients. Overall, FVC and DLCO remained stable or increased in 86.1% and 91.7% of patients, respectively, while HRCT was stable or improved in 81.4% of them. Previous and concurrent treatments, in particular, methotrexate, serology, age, sex, joint and lung disease duration were not associated with the outcome at univariate analysis. Conclusion: The management of RA-ILD patients remains a critical unmet medical need. Waiting for prospective controlled studies, ABA has shown a good safety profile in our cohort of Italian RA-ILD patients.
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- 2020
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40. Cardiovascular Imaging Techniques in Systemic Rheumatic Diseases
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Fabiola Atzeni, Marco Corda, Luigi Gianturco, Maurizio Porcu, Piercarlo Sarzi-Puttini, and Maurizio Turiel
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systemic rheumatic diseases ,coronary artery diseases ,plasma asymmetric dimethylarginine ,computed tomography ,atherosclerosis ,endothelial dysfunction ,Medicine (General) ,R5-920 - Abstract
The risk of cardiovascular (CV) events and mortality is significantly higher in patients with systemic rheumatic diseases than in the general population. Although CV involvement in such patients is highly heterogeneous and may affect various structures of the heart, it can now be diagnosed earlier and promptly treated. Various types of assessments are employed for the evaluation of CV risk such as transthoracic or transesophageal echocardiography, magnetic resonance imaging (MRI), and computed tomography (CT) to investigate valve abnormalities, pericardial disease, and ventricular wall motion defects. The diameter of coronary arteries can be assessed using invasive quantitative coronarography or intravascular ultrasound, and coronary flow reserve can be assessed using non-invasive transesophageal or transthoracic ultrasonography (US), MRI, CT, or positron emission tomography (PET) after endothelium-dependent vasodilation. Finally, peripheral circulation can be measured invasively using strain-gauge plethysmography in an arm after the arterial infusion of an endothelium-dependent vasodilator or non-invasively by means of US or MRI measurements of flow-mediated vasodilation of the brachial artery. All of the above are reliable methods of investigating CV involvement, but more recently, introduced use of speckle tracking echocardiography and 3-dimensional US are diagnostically more accurate.
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- 2018
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41. The Microbiome in Connective Tissue Diseases and Vasculitides: An Updated Narrative Review
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Rossella Talotta, Fabiola Atzeni, Maria Chiara Ditto, Maria Chiara Gerardi, and Piercarlo Sarzi-Puttini
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective. To provide a narrative review of the most recent data concerning the involvement of the microbiome in the pathogenesis of connective tissue diseases (CTDs) and vasculitides. Methods. The PubMed database was searched for articles using combinations of words or terms that included systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, Sjögren’s syndrome, undifferentiated and mixed CTD, vasculitis, microbiota, microbiome, and dysbiosis. Papers from the reference lists of the articles and book chapters were reviewed, and relevant publications were identified. Abstracts and articles written in languages other than English were excluded. Results. We found some evidence that dysbiosis participates in the pathogenesis of systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and Behçet’s disease, but there are still few data concerning the role of dysbiosis in other CTDs or vasculitides. Conclusions. Numerous studies suggest that alterations in human microbiota may be involved in the pathogenesis of inflammatory arthritides as a result of the aberrant activation of the innate and adaptive immune responses. Only a few studies have explored the involvement of dysbiosis in other CTDs or vasculitides, and further research is needed.
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- 2017
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42. Update on fibromyalgia
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Fabiola Atzeni, Marco Cazzola, and Piercarlo Sarzi-Puttini
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Fibromyalgia ,Diffuse pain ,Pharmacological therapy ,Physiotherapy ,Medicine - Abstract
IntroductionFibromyalgia (FM) is a chronic pain syndrome characterized by widespread pain, fatigue, sleep alterations, and distress. It affects at least 2% of the adult population. The etiology of FM is not completely understood, and the syndrome is influenced by stress, physical illness, and a variety of pain conditions. Emerging evidence indicates that augmented pain processing within the central nervous system plays a primary role in the pathophysiology of this disorder. Diagnosis may be difficult because of the multifaceted nature of the syndrome and its overlap with other chronically painful conditions. This article reviews the most recent data in the literature on FM.Materials and methodsThere are currently no instrumental tests or specific diagnostic markers for FM. In fact, many of the existing indicators are regarded as significant for research purposes only.ResultsDifferential diagnosis requires an extensive clinical examination and complete patient history. Chest-X-rays and abdominal ultrasonography are the first steps in the general evaluation of a patient with suspected FM.ConclusionsA variety of pharmacological treatments have been used to treat FM, including antidepressants, nonsteroidal anti-inflammatory drugs, opioids, sedatives, muscle relaxants, and antiepileptics. Physical exercise and multimodal cognitive-behavioral therapy seem to be the most widely accepted and beneficial forms of non-pharmacological therapy.
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- 2012
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43. The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis According to Th9-Related Responses
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Rossella Talotta, Angela Berzi, Andrea Doria, Alberto Batticciotto, Maria Chiara Ditto, Fabiola Atzeni, Piercarlo Sarzi-Puttini, and Daria Trabattoni
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biosimilars ,Th9 lymphocytes ,rheumatoid arthritis ,infliximab ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test. Methods: Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 μg/mL of infliximab originator (Remicade®) or 50 μg/mL of infliximab biosimilar (Remsima®) for 18 h. Th9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing, IL-9-secreting CD4+ T cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naïve from memory IL-9 producer cells. Results: Under unstimulated conditions, the drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7+, CD45RA− (central memory) and CCR7−, CD45RA− (effector memory) cells significantly increased in the group of inadequate responders, but no significant variation was observed after exposure to the biosimilar of infliximab. Conclusions: Th9 cells seem to be involved in the immune response to the epitopes of branded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both central and effector memory cells.
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- 2017
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44. Clinical Comparison of QUANTA Flash dsDNA Chemiluminescent Immunoassay with Four Current Assays for the Detection of Anti-dsDNA Autoantibodies
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Maria Infantino, Francesca Meacci, Chelsea Bentow, Peter Martis, Maurizio Benucci, Antonella Afeltra, Amelia Rigon, Fabiola Atzeni, Piercarlo Sarzi-Puttini, Mariangela Manfredi, and Michael Mahler
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Introduction. The objective of the present study was to compare QUANTA Flash dsDNA, a chemiluminescent immunoassay (CIA) on the BIO-FLASH, a rapid-response chemiluminescent analyzer, to three other anti-dsDNA antibody assays and to Crithidia luciliae indirect immunofluorescence test (CLIFT). Methods. In the first part of the study, 161 samples, 61 from patients suffering from systemic lupus erythematosus (SLE) and 100 from a disease control group, were tested by QUANTA Flash dsDNA CIA, QUANTA Lite dsDNA SC ELISA, BioPlex 2200 multiplex flow immunoassay (MFI), ImmuLisa dsDNA ELISA, and NOVA Lite CLIFT. A second cohort of 69 SLE patients was then tested by QUANTA Flash dsDNA and CLIFT to expand the study. Results. The overall qualitative agreements varied between 77.0% (NOVA Lite CLIFT versus QUANTA Lite) and 89.4% (ImmuLisa versus NOVA Lite CLIFT). The clinical sensitivities for the anti-dsDNA antibody tests varied from 8.2% (NOVA Lite CLIFT) to 54.1% (QUANTA Lite), while the clinical specificities varied from 88.0% (BioPlex 2200) to 100.0% (NOVA Lite CLIFT). Good correlation was found between QUANTA Flash dsDNA and NOVA Lite CLIFT. Conclusion. Significant variations among dsDNA methods were observed. QUANTA Flash dsDNA provides a good combination of sensitivity and specificity for the diagnosis of SLE and good agreement to CLIFT.
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- 2015
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45. TLR-4 and VEGF polymorphisms in chronic periaortitis.
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Fabiola Atzeni, Luigi Boiardi, Augusto Vaglio, Davide Nicoli, Enrico Farnetti, Alessandra Palmisano, Nicolò Pipitone, Davide Martorana, Gabriella Moroni, Selena Longhi, Francesco Bonatti, Carlo Buzio, and Carlo Salvarani
- Subjects
Medicine ,Science - Abstract
OBJECTIVE: Chronic periaortitis (CP) is a rare disease that is characterised by fibro-inflammatory tissue surrounding the abdominal aorta and has both non-aneurysmal (idiopathic retroperitoneal fibrosis [IRF]) and aneurysmal forms (inflammatory abdominal aortic aneurysm [IAAA]). We investigated whether toll-like receptor 4 (TLR-4) and vascular endothelial growth factor (VEGF) polymorphisms were associated with susceptibility to, and the clinical features of CP. METHODS: One hundred and two CP patients and 200 healthy controls were molecularly genotyped for TLR-4 gene polymorphism (+896 A/G) (rs4986790), VEGF mutations +936 C/T (rs3025039) and -634 C/G (rs2010963), and an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the VEGF promoter region. The patients were grouped on the basis of the type of CP (IRF or IAAA), and the presence or absence of established atherosclerotic disease (ischemic heart disease, cerebrovascular disease, and peripheral arterial disease). RESULTS: There were no significant differences in the distribution of the studied polymorphisms between the patients and controls. However, carriage of the +936 T allele was significantly more frequent in the patients with IRF than in those with IAAA (26.5% vs 5.3%; p = 0.046; OR 6.49 [95% CI 0.82-51.54]). There were significantly more carriers of the I allele among the patients with ureteral obstruction (83.8% vs 58.8%; p = 0.006; OR 3.63 [95% CI 1.42-9.28]) and those who received conservative treatment (48.5% vs 23.5%; p = 0.015; OR 3.06 [95% CI 1.22-7.721]) than among those without, and II homozygosity was significantly more frequent in the patients with deep vein thrombosis than in those without (30.4% vs 11.7%, p = 0.031; OR 3.31 [95% CI 1.07-10.21]). CONCLUSION: The VEGF +936 C/T polymorphism may be associated with an increased risk of developing the non-aneurysmal IRF form of CP. Carriers of the I allele and II homozygosity are respectively at increased risk of developing ureteral obstruction and deep vein thrombosis.
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- 2013
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46. Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: clues for the pathogenesis.
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Gianfranco Ferraccioli, Barbara Tolusso, Francesca Bobbio-Pallavicini, Elisa Gremese, Viviana Ravagnani, Maurizio Benucci, Edoardo Podestà, Fabiola Atzeni, Alice Mannocci, Domenico Biasi, Mariangela Manfredi, Piercarlo Sarzi-Puttini, Bruno Laganà, and Carlomaurizio Montecucco
- Subjects
Medicine ,Science - Abstract
OBJECTIVE: To find out whether a high number of auto-antibodies can increase the probability of a "good-EULAR response" and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT). PATIENTS AND METHODS: One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined. RESULTS: At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count 52.1 IU/ml (OR = 8.37) and BAFF levels
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- 2012
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47. Cost Effectiveness Analysis of Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis. A Systematic Review Literature
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Maurizio Benucci, Gianantonio Saviola, Mariangela Manfredi, Piercarlo Sarzi-Puttini, and Fabiola Atzeni
- Subjects
Diseases of the musculoskeletal system ,RC925-935 - Abstract
The cost effectiveness of treatments that have changed the “natural history” of a chronic progressive disease needs to be evaluated over the long term. Disease-modifying antirheumatic drugs (DMARDs) are the standard treatment of rheumatoid arthritis (RA) and should be started as early as possible. A number of studies have shown that they are effective in improving disease activity and function, and in joint damage. Our review was focused on revision and critical evaluation of the studies including the literature on cost effectiveness of DMARDs (cyclosporine A, sulphasalazine, leflunomide, and methotrexate). The European League Against Rheumatism (EULAR) recommendations showed that traditional DMARDs are cost effective at the time of disease onset. They are less expensive than biological DMARDs and can be useful in controlling disease activity in early RA.
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- 2011
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48. Conventional, biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors and varicella zoster virus
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Fabiola Atzeni, Francesco Gozza, Agostino Riva, Alessandra Alciati, and James Galloway
- Subjects
Pharmacology ,Pharmacology (medical) ,General Medicine - Published
- 2023
49. Diagnosis and management of cardiovascular risk in rheumatoid arthritis: main challenges and research agenda
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Fabiola Atzeni, Silvia Maiani, Marco Corda, and Javier Rodríguez-Carrio
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Immunology ,Immunology and Allergy - Published
- 2023
50. Targeting the interleukin-5 pathway in EGPA: evidence, uncertainties and opportunities
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Alvise Berti, Fabiola Atzeni, Lorenzo Dagna, Stefano Del Giacco, Giacomo Emmi, Carlo Salvarani, and Augusto Vaglio
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
Only a minority of patients with eosinophilic granulomatosis with polyangiitis (EGPA) can be weaned-off glucocorticoids (GC) using conventional treatment strategies. The development of biological agents specifically inhibiting the IL-5 pathway provided the opportunity to treat EGPA by targeting one of the crucial regulators of eosinophils, reducing the GC dose required to control the disease.The anti-IL-5 antibody mepolizumab at the dose of 300 mg/4 weeks has proven to be safe and effective in EGPA. While relapsing patients—who often experience recurrent respiratory manifestations—benefit from this treatment, data are not enough to support its use combined with GC alone in remission induction of severe active forms, or in remission maintenance without conventional immunosuppressants in patients with vasculitic manifestations. Ultimately, the profile of the best candidate for mepolizumab is still unclear.Several real-life reports suggest that mepolizumab at the dose of 100 mg/4 weeks, approved for eosinophilic asthma/chronic rhinosinusitis with nasal polyposis (CRSwNP), effectively maintains remission of EGPA-related asthma and, to a lesser extent, CRSwNP. Preliminary data on the IL-5 pathway-inhibitors benralizumab and reslizumab in EGPA as steroid-sparing agents are also accumulating.Overall, it remains to be proven whether targeting the IL-5 pathway could block progression of organ damage in EGPA, on top of reducing relapses and sparing GC. Other disease-related factors further complicate the understanding of the real anti-IL-5 agent efficacy, such as the lack of a clear definition of remission, of an effective tool to measure disease activity, and of well-defined treat-to-target approaches or goals of treatment.
- Published
- 2022
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