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1. Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

Author

Di Matteo, A, Moscioni, E, Lommano, M, Cipolletta, E, Smerilli, G, Farah, S, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Carotti, M, Carrara, G, Cazenave, T, Corradini, D, Cosatti, M, de Agustin, J, Destro Castaniti, G, Di Carlo, M, Di Donato, E, Di Geso, L, Elliott, A, Fodor, D, Francioso, F, Gabba, A, Hernandez-Diaz, C, Horvath, R, Hurnakova, J, Jesus, D, Marin, J, Martire, M, Mashadi Mirza, R, Massarotti, M, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosa, J, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Scioscia, C, Scire, C, Tamas, M, Tanimura, S, Ventura-Rios, L, Villota-Eraso, C, Villota, O, Voulgari, P, Vreju, F, Vukatana, G, Hereter, J, Zanetti, A, Grassi, W, Filippucci, E, Di Matteo A., Moscioni E., Lommano M. G., Cipolletta E., Smerilli G., Farah S., Airoldi C., Aydin S. Z., Becciolini A., Bonfiglioli K., Carotti M., Carrara G., Cazenave T., Corradini D., Cosatti M. A., de Agustin J. J., Destro Castaniti G. M., Di Carlo M., Di Donato E., Di Geso L., Elliott A., Fodor D., Francioso F., Gabba A., Hernandez-Diaz C., Horvath R., Hurnakova J., Jesus D., Marin J., Martire M. V., Mashadi Mirza R., Massarotti M., Musca A. A., Nair J., Okano T., Papalopoulos I., Rosa J., Rosemffet M., Rovisco J., Rozza D., Salaffi F., Scioscia C., Scire C. A., Tamas M. -M., Tanimura S., Ventura-Rios L., Villota-Eraso C., Villota O., Voulgari P. V., Vreju F. A., Vukatana G., Hereter J. Z., Zanetti A., Grassi W., Filippucci E., Di Matteo, A, Moscioni, E, Lommano, M, Cipolletta, E, Smerilli, G, Farah, S, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Carotti, M, Carrara, G, Cazenave, T, Corradini, D, Cosatti, M, de Agustin, J, Destro Castaniti, G, Di Carlo, M, Di Donato, E, Di Geso, L, Elliott, A, Fodor, D, Francioso, F, Gabba, A, Hernandez-Diaz, C, Horvath, R, Hurnakova, J, Jesus, D, Marin, J, Martire, M, Mashadi Mirza, R, Massarotti, M, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosa, J, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Scioscia, C, Scire, C, Tamas, M, Tanimura, S, Ventura-Rios, L, Villota-Eraso, C, Villota, O, Voulgari, P, Vreju, F, Vukatana, G, Hereter, J, Zanetti, A, Grassi, W, Filippucci, E, Di Matteo A., Moscioni E., Lommano M. G., Cipolletta E., Smerilli G., Farah S., Airoldi C., Aydin S. Z., Becciolini A., Bonfiglioli K., Carotti M., Carrara G., Cazenave T., Corradini D., Cosatti M. A., de Agustin J. J., Destro Castaniti G. M., Di Carlo M., Di Donato E., Di Geso L., Elliott A., Fodor D., Francioso F., Gabba A., Hernandez-Diaz C., Horvath R., Hurnakova J., Jesus D., Marin J., Martire M. V., Mashadi Mirza R., Massarotti M., Musca A. A., Nair J., Okano T., Papalopoulos I., Rosa J., Rosemffet M., Rovisco J., Rozza D., Salaffi F., Scioscia C., Scire C. A., Tamas M. -M., Tanimura S., Ventura-Rios L., Villota-Eraso C., Villota O., Voulgari P. V., Vreju F. A., Vukatana G., Hereter J. Z., Zanetti A., Grassi W., and Filippucci E.

Abstract

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases.

Published
2023

2. Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study

Author

Di Matteo, A, Cipolletta, E, Castaniti, G, Smerilli, G, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Bruns, A, Carrara, G, Cazenave, T, Ciapetti, A, Cosatti, M, de Agustin, J, Di Carlo, M, Di Donato, E, Di Geso, L, Duran, E, Elliott, A, Estrach, C, Farisogullari, B, Fiorenza, A, Fodor, D, Gabba, A, Hernandez-Diaz, C, Huang, F, Hurnakova, J, Li, L, Jesus, D, Karadag, O, Martire, M, Massarotti, M, Michelena, X, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Satulu, I, Scioscia, C, Scire, C, Sun, F, Tamas, M, Tanimura, S, Ventura-Rios, L, Voulgari, P, Vreju, F, Vukatana, G, Wong, E, Yang, J, Hereter, J, Zanetti, A, Grassi, W, Filippucci, E, Di Matteo A., Cipolletta E., Castaniti G. M. D., Smerilli G., Airoldi C., Aydin S. Z., Becciolini A., Bonfiglioli K., Bruns A., Carrara G., Cazenave T., Ciapetti A., Cosatti M. A., de Agustin J. J., Di Carlo M., Di Donato E., Di Geso L., Duran E., Elliott A., Estrach C., Farisogullari B., Fiorenza A., Fodor D., Gabba A., Hernandez-Diaz C., Huang F., Hurnakova J., Li L., Jesus D., Karadag O., Martire M. V., Massarotti M., Michelena X., Musca A. A., Nair J., Okano T., Papalopoulos I., Rosemffet M., Rovisco J., Rozza D., Salaffi F., Satulu I., Scioscia C., Scire C. A., Sun F., Tamas M. -M., Tanimura S., Ventura-Rios L., Voulgari P. V., Vreju F. A., Vukatana G., Wong E., Yang J., Hereter J. Z., Zanetti A., Grassi W., Filippucci E., Di Matteo, A, Cipolletta, E, Castaniti, G, Smerilli, G, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Bruns, A, Carrara, G, Cazenave, T, Ciapetti, A, Cosatti, M, de Agustin, J, Di Carlo, M, Di Donato, E, Di Geso, L, Duran, E, Elliott, A, Estrach, C, Farisogullari, B, Fiorenza, A, Fodor, D, Gabba, A, Hernandez-Diaz, C, Huang, F, Hurnakova, J, Li, L, Jesus, D, Karadag, O, Martire, M, Massarotti, M, Michelena, X, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Satulu, I, Scioscia, C, Scire, C, Sun, F, Tamas, M, Tanimura, S, Ventura-Rios, L, Voulgari, P, Vreju, F, Vukatana, G, Wong, E, Yang, J, Hereter, J, Zanetti, A, Grassi, W, Filippucci, E, Di Matteo A., Cipolletta E., Castaniti G. M. D., Smerilli G., Airoldi C., Aydin S. Z., Becciolini A., Bonfiglioli K., Bruns A., Carrara G., Cazenave T., Ciapetti A., Cosatti M. A., de Agustin J. J., Di Carlo M., Di Donato E., Di Geso L., Duran E., Elliott A., Estrach C., Farisogullari B., Fiorenza A., Fodor D., Gabba A., Hernandez-Diaz C., Huang F., Hurnakova J., Li L., Jesus D., Karadag O., Martire M. V., Massarotti M., Michelena X., Musca A. A., Nair J., Okano T., Papalopoulos I., Rosemffet M., Rovisco J., Rozza D., Salaffi F., Satulu I., Scioscia C., Scire C. A., Sun F., Tamas M. -M., Tanimura S., Ventura-Rios L., Voulgari P. V., Vreju F. A., Vukatana G., Wong E., Yang J., Hereter J. Z., Zanetti A., Grassi W., and Filippucci E.

Abstract

Objectives. To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. Methods. In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light’s kappa, Cohen’s kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. Results. Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light’s kappa: 0.77 (0.76–0.78), 0.72 (0.71–0.73), respectively; PABAK: 0.86 (0.86–0.87), 0.73 (0.73–0.74), respectively], followed by enthesophytes/calcifications [Light’s kappa: 0.65 (0.64–0.65), PABAK: 0.67 (0.67–0.68)]. This was moderate for entheseal thickening [Light’s kappa: 0.41 (0.41–0.42), PABAK: 0.41 (0.40–0.42)], and fair for hypoechoic areas [Light’s kappa: 0.37 (0.36–0.38); PABAK: 0.37 (0.37–0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. Conclusions. The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Published
2022

3. Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients

Author

Thomas, K. Lazarini, A. Kaltsonoudis, E. Drosos, A. Papalopoulos, I. Sidiropoulos, P. Tsatsani, P. Gazi, S. Pantazi, L. Boki, K.A. Katsimbri, P. Boumpas, D. Fragkiadaki, K. Tektonidou, M. Sfikakis, P.P. Karagianni, K. Sakkas, L.I. Grika, E.P. Vlachoyiannopoulos, P.G. Evangelatos, G. Iliopoulos, A. Dimitroulas, T. Garyfallos, A. Melissaropoulos, K. Georgiou, P. Areti, M. Georganas, C. Vounotrypidis, P. Kitas, G.D. Vassilopoulos, D.

Abstract

Background: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. Methods: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. Results: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. Conclusion: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors. © The Author(s), 2020.

Published
2020

4. PATTERNS OF BIOLOGIC DMARD MONOTHERAPY IN A LARGE NATIONWIDE RHEUMATOID ARTHRITIS COHORT: DATA FROM 1036 PATIENTS

Author

Thomas, K. Kaltsonoudis, E. Drosos, A. Papalopoulos, I. and Sidiropoulos, P. Katsimbri, P. Boumpas, D. Tsatsani, P. and Gazi, S. Grika, E. P. Vlachoyiannopoulos, P. G. Fragiadaki, K. Tektonidou, M. Sfikakis, P. P. Karagianni, K. Sakkas, L. I. Pantazi, L. Boki, K. Dimitroulas, T. Garyfallos, A. Kasimos, D. Evangelatos, G. Iliopoulos, A. Georganas, C. Vounotrypidis, P. Areti, M. Georgiou, P. Delis, K. and Mavragani, K. Bournazos, I. Katsifis, G. Mavromatis, C. and Kitas, G. D. Vassilopoulos, D.

Published
2017

6. Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study

Author

Andrea Di Matteo, Edoardo Cipolletta, Giulia Maria Destro Castaniti, Gianluca Smerilli, Carla Airoldi, Sibel Zehra Aydin, Andrea Becciolini, Karina Bonfiglioli, Alessandra Bruns, Greta Carrara, Tomas Cazenave, Alessandro Ciapetti, Micaela Ana Cosatti, Juan José de Agustín, Marco Di Carlo, Eleonora Di Donato, Luca Di Geso, Emine Duran, Ashley Elliott, Cristina Estrach, Bayram Farisogulları, Alessia Fiorenza, Daniela Fodor, Alessandra Gabba, Cristina Hernández-Díaz, Feng Huang, Jana Hurnakova, Ling Li, Diogo Jesus, Omer Karadag, Maria Victoria Martire, Marco Massarotti, Xabier Michelena, Alice Andreea Musca, Jagdish Nair, Tadashi Okano, Ioannis Papalopoulos, Marcos Rosemffet, João Rovisco, Davide Rozza, Fausto Salaffi, Iulia Satulu, Crescenzio Scioscia, Carlo Alberto Scirè, Fei Sun, Maria-Magdalena Tamas, Shun Tanimura, Lucio Ventura-Rios, Paraksevi V Voulgari, Florentin Ananu Vreju, Gentiana Vukatana, Ernest Wong, Jinshui Yang, Johana Zacariaz Hereter, Anna Zanetti, Walter Grassi, Emilio Filippucci, Di Matteo, A, Cipolletta, E, Castaniti, G, Smerilli, G, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Bruns, A, Carrara, G, Cazenave, T, Ciapetti, A, Cosatti, M, de Agustin, J, Di Carlo, M, Di Donato, E, Di Geso, L, Duran, E, Elliott, A, Estrach, C, Farisogullari, B, Fiorenza, A, Fodor, D, Gabba, A, Hernandez-Diaz, C, Huang, F, Hurnakova, J, Li, L, Jesus, D, Karadag, O, Martire, M, Massarotti, M, Michelena, X, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Satulu, I, Scioscia, C, Scire, C, Sun, F, Tamas, M, Tanimura, S, Ventura-Rios, L, Voulgari, P, Vreju, F, Vukatana, G, Wong, E, Yang, J, Hereter, J, Zanetti, A, Grassi, W, and Filippucci, E

Subjects
power Doppler signal, Internet, reliability, ultrasound, Reproducibility of Results, seronegative spondyloarthriti, Ultrasonography, Doppler, Enthesopathy, enthesiti, PsA, Rheumatology, Humans, Pharmacology (medical), multicenter international study, Ultrasonography
Abstract

Objectives To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. Methods In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light’s kappa, Cohen’s kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. Results Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light’s kappa: 0.77 (0.76–0.78), 0.72 (0.71–0.73), respectively; PABAK: 0.86 (0.86–0.87), 0.73 (0.73–0.74), respectively], followed by enthesophytes/calcifications [Light’s kappa: 0.65 (0.64–0.65), PABAK: 0.67 (0.67–0.68)]. This was moderate for entheseal thickening [Light’s kappa: 0.41 (0.41–0.42), PABAK: 0.41 (0.40–0.42)], and fair for hypoechoic areas [Light’s kappa: 0.37 (0.36–0.38); PABAK: 0.37 (0.37–0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. Conclusions The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis.

Published
2022
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7. Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study

Author

Andrea Di Matteo, Erica Moscioni, Maria Giovanna Lommano, Edoardo Cipolletta, Gianluca Smerilli, Sonia Farah, Carla Airoldi, Sibel Zehra Aydin, Andrea Becciolini, Karina Bonfiglioli, Marina Carotti, Greta Carrara, Tomas Cazenave, Davide Corradini, Micaela Ana Cosatti, Juan Josè de Agustin, Giulia Maria Destro Castaniti, Marco Di Carlo, Eleonora Di Donato, Luca Di Geso, Ashley Elliott, Daniela Fodor, Francesca Francioso, Alessandra Gabba, Cristina Hernández-Díaz, Rudolf Horvath, Jana Hurnakova, Diogo Jesus, Josefina Marin, Maria Victoria Martire, Riccardo Mashadi Mirza, Marco Massarotti, Alice Andreea Musca, Jagdish Nair, Tadashi Okano, Ioannis Papalopoulos, Javier Rosa, Marcos Rosemffet, João Rovisco, Davide Rozza, Fausto Salaffi, Crescenzio Scioscia, Carlo Alberto Scirè, Maria-Magdalena Tamas, Shun Tanimura, Lucio Ventura-Rios, Catalina Villota-Eraso, Orlando Villota, Paraskevi V. Voulgari, Florentin Ananu Vreju, Gentiana Vukatana, Johana Zacariaz Hereter, Anna Zanetti, Walter Grassi, Emilio Filippucci, Institut Català de la Salut, [Di Matteo A] Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy. Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom. [Moscioni E, Lommano MG, Cipolletta E, Smerilli G, Farah S] Rheumatology Unit, Department of Clinical and Molecular Sciences, 'Carlo Urbani' Hospital, Polytechnic University of Marche, Ancona, Italy. [de Agustin JJ] Servei de Reumatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Di Matteo, A, Moscioni, E, Lommano, M, Cipolletta, E, Smerilli, G, Farah, S, Airoldi, C, Aydin, S, Becciolini, A, Bonfiglioli, K, Carotti, M, Carrara, G, Cazenave, T, Corradini, D, Cosatti, M, de Agustin, J, Destro Castaniti, G, Di Carlo, M, Di Donato, E, Di Geso, L, Elliott, A, Fodor, D, Francioso, F, Gabba, A, Hernandez-Diaz, C, Horvath, R, Hurnakova, J, Jesus, D, Marin, J, Martire, M, Mashadi Mirza, R, Massarotti, M, Musca, A, Nair, J, Okano, T, Papalopoulos, I, Rosa, J, Rosemffet, M, Rovisco, J, Rozza, D, Salaffi, F, Scioscia, C, Scire, C, Tamas, M, Tanimura, S, Ventura-Rios, L, Villota-Eraso, C, Villota, O, Voulgari, P, Vreju, F, Vukatana, G, Hereter, J, Zanetti, A, Grassi, W, and Filippucci, E

Subjects
reliability, Otros calificadores::Otros calificadores::/diagnóstico por imagen [Otros calificadores], General Medicine, muscle echogenicity, sarcopenia, enfermedades musculoesqueléticas::enfermedades reumáticas [ENFERMEDADES], Músculs - Ecografia, Musculoskeletal Diseases::Rheumatic Diseases [DISEASES], rheumatic diseases, diagnóstico::técnicas y procedimientos diagnósticos::diagnóstico por imagen::ecografía [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Ultrasonography [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], musculoskeletal ultrasound, rheumatic disease, Reumatisme - Ecografia, Other subheadings::Other subheadings::/diagnostic imaging [Other subheadings]
Abstract

Muscle echogenicity; Musculoskeletal ultrasound; Rheumatic diseases Ecogenicidad muscular; Ecografía musculoesquelética; Enfermedades reumáticas Ecogenicitat muscular; Ecografia musculoesquelètica; Malalties reumàtiques Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases. Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0–3) and a continuous quantitative measurement (“VAS echogenicity,” 0–100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall’s Tau and Pearson’s Rho coefficients. Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57–0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68–0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. “VAS echogenicity” showed a high reliability both in the inter-observer [ICC = 0.80 (0.75–0.85)] and intra-observer [ICC = 0.88 (0.88–0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and “VAS echogenicity” [ICC = 0.52 (0.50–0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively). Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases. RH and JH were supported by Ministry of Health, Czech Republic – conceptual development of research organization, Motol University Hospital, Prague, Czech Republic (00064203).

Published
2023
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8. Reliability assessment of ultrasound muscle echogenicity in patients with rheumatic diseases: Results of a multicenter international web-based study.

Author

Di Matteo A, Moscioni E, Lommano MG, Cipolletta E, Smerilli G, Farah S, Airoldi C, Aydin SZ, Becciolini A, Bonfiglioli K, Carotti M, Carrara G, Cazenave T, Corradini D, Cosatti MA, de Agustin JJ, Destro Castaniti GM, Di Carlo M, Di Donato E, Di Geso L, Elliott A, Fodor D, Francioso F, Gabba A, Hernández-Díaz C, Horvath R, Hurnakova J, Jesus D, Marin J, Martire MV, Mashadi Mirza R, Massarotti M, Musca AA, Nair J, Okano T, Papalopoulos I, Rosa J, Rosemffet M, Rovisco J, Rozza D, Salaffi F, Scioscia C, Scirè CA, Tamas MM, Tanimura S, Ventura-Rios L, Villota-Eraso C, Villota O, Voulgari PV, Vreju FA, Vukatana G, Hereter JZ, Zanetti A, Grassi W, and Filippucci E

Abstract

Objectives: To investigate the inter/intra-reliability of ultrasound (US) muscle echogenicity in patients with rheumatic diseases., Methods: Forty-two rheumatologists and 2 radiologists from 13 countries were asked to assess US muscle echogenicity of quadriceps muscle in 80 static images and 20 clips from 64 patients with different rheumatic diseases and 8 healthy subjects. Two visual scales were evaluated, a visual semi-quantitative scale (0-3) and a continuous quantitative measurement ("VAS echogenicity," 0-100). The same assessment was repeated to calculate intra-observer reliability. US muscle echogenicity was also calculated by an independent research assistant using a software for the analysis of scientific images (ImageJ). Inter and intra reliabilities were assessed by means of prevalence-adjusted bias-adjusted Kappa (PABAK), intraclass correlation coefficient (ICC) and correlations through Kendall's Tau and Pearson's Rho coefficients., Results: The semi-quantitative scale showed a moderate inter-reliability [PABAK = 0.58 (0.57-0.59)] and a substantial intra-reliability [PABAK = 0.71 (0.68-0.73)]. The lowest inter and intra-reliability results were obtained for the intermediate grades (i.e., grade 1 and 2) of the semi-quantitative scale. "VAS echogenicity" showed a high reliability both in the inter-observer [ICC = 0.80 (0.75-0.85)] and intra-observer [ICC = 0.88 (0.88-0.89)] evaluations. A substantial association was found between the participants assessment of the semi-quantitative scale and "VAS echogenicity" [ICC = 0.52 (0.50-0.54)]. The correlation between these two visual scales and ImageJ analysis was high (tau = 0.76 and rho = 0.89, respectively)., Conclusion: The results of this large, multicenter study highlighted the overall good inter and intra-reliability of the US assessment of muscle echogenicity in patients with different rheumatic diseases., Competing Interests: SA received honoraria from AbbVie, Celgene, UCB, Novartis, Janssen, Pfizer, and Sanofi. AB served as a speaker for AbbVie, Amgen, Sanofi-Genzyme, and UCB, outside the submitted work. EF had received speaking fees from AbbVie, Amgen, BMS, Janssen, Lilly, Novartis, Roche, Pfizer, and UCB, outside the submitted work. WG had received speaking fees from Celltrion and Pfizer, outside the submitted work., (Copyright © 2023 Di Matteo, Moscioni, Lommano, Cipolletta, Smerilli, Farah, Airoldi, Aydin, Becciolini, Bonfiglioli, Carotti, Carrara, Cazenave, Corradini, Cosatti, de Agustin, Destro Castaniti, Di Carlo, Di Donato, Di Geso, Elliott, Fodor, Francioso, Gabba, Hernández-Díaz, Horvath, Hurnakova, Jesus, Marin, Martire, Mashadi Mirza, Massarotti, Musca, Nair, Okano, Papalopoulos, Rosa, Rosemffet, Rovisco, Rozza, Salaffi, Scioscia, Scirè, Tamas, Tanimura, Ventura-Rios, Villota-Eraso, Villota, Voulgari, Vreju, Vukatana, Hereter, Zanetti, Grassi and Filippucci.)

Published
2023
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9. Reliability assessment of the definition of ultrasound enthesitis in SpA: results of a large, multicentre, international, web-based study.

Author

Di Matteo A, Cipolletta E, Destro Castaniti GM, Smerilli G, Airoldi C, Aydin SZ, Becciolini A, Bonfiglioli K, Bruns A, Carrara G, Cazenave T, Ciapetti A, Cosatti MA, de Agustín JJ, Di Carlo M, Di Donato E, Di Geso L, Duran E, Elliott A, Estrach C, Farisogulları B, Fiorenza A, Fodor D, Gabba A, Hernández-Díaz C, Huang F, Hurnakova J, Li L, Jesus D, Karadag O, Martire MV, Massarotti M, Michelena X, Musca AA, Nair J, Okano T, Papalopoulos I, Rosemffet M, Rovisco J, Rozza D, Salaffi F, Satulu I, Scioscia C, Scirè CA, Sun F, Tamas MM, Tanimura S, Ventura-Rios L, Voulgari PV, Vreju FA, Vukatana G, Wong E, Yang J, Zacariaz Hereter J, Zanetti A, Grassi W, and Filippucci E

Subjects
Humans, Reproducibility of Results, Ultrasonography methods, Ultrasonography, Doppler methods, Internet, Enthesopathy diagnostic imaging
Abstract

Objectives: To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA., Methods: In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs., Results: Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76-0.78), 0.72 (0.71-0.73), respectively; PABAK: 0.86 (0.86-0.87), 0.73 (0.73-0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64-0.65), PABAK: 0.67 (0.67-0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41-0.42), PABAK: 0.41 (0.40-0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36-0.38); PABAK: 0.37 (0.37-0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation., Conclusions: The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2022
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10. Rheumatoid arthritis patients initiating rituximab with low number of previous bDMARDs failures may effectively reduce rituximab dose and experience fewer serious adverse events than patients on full dose: a 5-year cohort study.

Author

Bertsias A, Avgoustidis N, Papalopoulos I, Repa A, Kougkas N, Kalogiannaki E, Bertsias G, Flouri I, and Sidiropoulos P

Subjects
Cohort Studies, Female, Humans, Middle Aged, Prednisolone, Prospective Studies, Rituximab adverse effects, Arthritis, Rheumatoid drug therapy
Abstract

Background: Rituximab is used for the treatment of active rheumatoid arthritis. In the present study, we examined the long-term flare risk and safety of reduced doses of rituximab., Patients-Methods: This was a prospective, observational, single-center study of patients starting rituximab on standard dose (SD). Patients were switched to low dose (LD) (1 g every 6 months), based on the treating rheumatologist's decision after having achieved sustained clinical responses, while the rest of the patients continued on standard dose (SD). During a 60-month period, we assessed (Kaplan-Meier survival analysis) the relapse rate (increase ≥ 1.2 in DAS28-ESR for ≥ 6 months) and discontinuations due to treatment failure in the low dose group, and we compared the incidence of serious adverse events (SAEs) between LD and SD groups., Results: Out of 361 patients [females 83.4%, mean age 61.9 (10.6) years, seropositive 50.3%, median total comorbidities count 4], 81 patients (22.4%) entered LD in a median time of 24 months (95% CI 18-30 months). Seropositivity (OR 1.823), more than 2 previous bDMARDs failures (OR 0.428), and DAS28 < 4.88 at 6 months (OR 2.329) predicted the odds of entering LD (p < 0.05 for all). During 60 months of follow-up, only 7.5% of patients on LD relapsed. Patients on LD had significantly less SAEs and all-cause hospitalizations as compared to the SD group (p < 0.05 for all). Linear regression analysis showed that previous hospitalization while on bDMARDs (p < 0.0001), use of prednisolone > 5 mg/day while on rituximab (p < 0.0001), and a history of ≥ 2 previous csDMARDs (p = 0.041) predicted the risk of SAEs., Conclusion: In a cohort of patients with established RA and significant comorbidities who taper rituximab after substantial initial disease activity improvement, a low rate of relapses and lower risk of SAEs compared to SD were recorded. Seropositivity, a lower number of previous bDMARDs use, and lower DAS28 at 6 months predicted the probability of entering the LD regimen., (© 2022. The Author(s).)

Published
2022
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11. Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients.

Author

Thomas K, Lazarini A, Kaltsonoudis E, Drosos A, Papalopoulos I, Sidiropoulos P, Tsatsani P, Gazi S, Pantazi L, Boki KA, Katsimbri P, Boumpas D, Fragkiadaki K, Tektonidou M, Sfikakis PP, Karagianni K, Sakkas LI, Grika EP, Vlachoyiannopoulos PG, Evangelatos G, Iliopoulos A, Dimitroulas T, Garyfallos A, Melissaropoulos K, Georgiou P, Areti M, Georganas C, Vounotrypidis P, Kitas GD, and Vassilopoulos D

Abstract

Background: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA., Methods: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded., Results: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR<3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to <5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA [odds ratio (OR) = 2.29 p  < 0.001] whereas advanced age (OR = 0.98, p  = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p  < 0.001), use of GCs (OR = 0.75, p  = 0.037) or ⩾2 bDMARDs (OR = 0.61, p  = 0.002), high co-morbidity index (OR = 0.86, p  = 0.011) and obesity (OR = 0.62, p  = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR >3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs., Conclusion: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2020.)

Published
2020
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12. In early arthritis patients, high HAQ at baseline and DAS28 at three months predict suboptimal outcomes at two years: a retrospective cohort study.

Author

Fanouriakis A, Papalopoulos I, Gergianaki I, Spyrou G, Erden A, Rapsomaniki P, Terizaki M, Avgoustidis N, Repa A, Kougkas N, Bertsias G, Boumpas DT, and Sidiropoulos PI

Subjects
Adult, Aged, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid physiopathology, Clinical Decision-Making, Disease Progression, Female, Health Status, Humans, Male, Middle Aged, Predictive Value of Tests, Remission Induction, Retrospective Studies, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Turkey, Arthritis, Rheumatoid diagnosis, Decision Support Techniques, Disability Evaluation
Abstract

Objectives: Early arthritis clinics (EAC) aim to improve rheumatoid arthritis (RA) outcomes by tailoring treatment targeting to remission. Our aim was to analyse disease course and relevant predictors over 2 years in early arthritis; we also assessed the applicability of the "treat-to-target approach" in a real-life EAC., Methods: Patients with early arthritis recruited at the EAC of the University Hospital of Heraklion were followed prospectively according to a follow-up protocol for two years, without implementing a pre-specified treatment protocol, to capture real-life practices. Early predictors of "suboptimal outcomes" (high disease activity or HAQ>1.0 at 2 years) and biologic DMARD (bDMARD) initiation were evaluated with multivariate logistic regression. Intensification of treatment at 3 and 6 months and subsequent long-term outcome were also assessed., Results: 251 patients [RA (n=188), undifferentiated arthritis (n=63)] were included. Although both DAS28 and HAQ at 2 years improved significantly compared to baseline in RA patients [mean (SD) DAS28 and median (IQR) HAQ 3.70 (1.32) and 0.44 (0.75) at 2 years, p<0.001 for both compared to baseline], 43.7% still had moderate and 18.8% high disease activity. The most powerful predictor of suboptimal outcomes or bDMARD initiation in RA was high disease activity at three months (adjusted odds ratio 2.22 and 2.62, respectively). At three and six months 72.8% and 62.4% of patients with medium/high disease activity received treatment intensification, which resulted in significant decrease in disease activity at 2 years (p<0.001 for ΔDAS28)., Conclusions: DAS28 at three months was the most powerful predictor of suboptimal disease outcome during a 2-year follow-up in early RA. Despite significant DAS reductions, more than 50% of patients have active disease at two years. Failure to fully implement the treat-to-target strategy in our cohort could account for the low remission rates.

Published
2018

13. Canakinumab for recurrent rheumatic disease associated-pericarditis: a case series with long-term follow-up.

Author

Kougkas N, Fanouriakis A, Papalopoulos I, Bertsias G, Avgoustidis N, Repa A, and Sidiropoulos P

Subjects
Adult, Antibodies, Monoclonal, Humanized, Female, Follow-Up Studies, Humans, Interleukin-1beta, Male, Middle Aged, Pericarditis etiology, Recurrence, Time Factors, Antibodies, Monoclonal therapeutic use, Pericarditis drug therapy, Rheumatic Diseases complications
Published
2018
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14. Multicenter Cross-sectional Study of Patients with Rheumatoid Arthritis in Greece: Results from a cohort of 2.491 patients.

Author

Thomas K, Lazarini A, Kaltsonoudis E, Drosos A, Papalopoulos I, Sidiropoulos P, Katsimbri P, Boumpas D, Tsatsani P, Gazi S, Fragkiadaki K, Tektonidou M, Sfikakis PP, Pantazi L, Boki KA, Grika EP, Vlachoyiannopoulos PG, Karagianni K, Sakkas LI, Dimitroulas T, Garyfallos A, Kassimos D, Evangelatos G, Iliopoulos A, Areti M, Georganas C, Melissaropoulos K, Georgiou P, Vounotrypidis P, Ntelis K, Mavragani CP, Bournazos I, Katsifis G, Mavrommatis C, Kitas GD, and Vassilopoulos D

Abstract

Aim of the Study: To evaluate the current disease characteristics, treatment and comorbidities of rheumatoid arthritis (RA) in Greece., Methods: Multicenter, cross-sectional study with a 9-month recruitment period between 2015 and 2016. Demographics, disease characteristics, treatment and comorbidities were collected via a web-based platform., Results: 2.491 RA patients were recruited: 96% from tertiary referral centers, 79% were females with a mean age of 63.1 years and disease duration of 9.9 years. Fifty-two percent were rheumatoid factor and/or anti-CCP positive, while 41% had erosive disease. Regarding treatment, 82% were on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs), 42% on biologic DMARDs (TNFi: 22%, non-TNFi: 20%) and 40% on corticosteroids (mean daily dose: 5.2 mg). Despite therapy, 36% of patients had moderate and 12% high disease activity. The most frequent comorbidities were hypertension (42%), hyperlipidemia (33%), osteoporosis (29%), diabetes mellitus (15%) and depression (12%). Latent tuberculosis infection (positive tuberculin skin test or interferon gamma release assay) was diagnosed in 13 and 15.3% of patients, respectively. Regarding chronic viral infections, 6.2% had history of herpes zoster while 2% and 0.7% had chronic hepatitis B and C virus infection, respectively. A history of serious infection was documented in 9.6%. Only 36% and 52% of the participants had ever been vaccinated against pneumococcus and influenza virus, respectively., Conclusion: This is one of the largest epidemiologic studies providing valuable data regarding the current RA characteristics in Greece. Half of patients were seropositive but despite therapy, half displayed residual disease activity, while preventive vaccination was limited., (© 2018 The Mediterranean Journal of Rheumatology (MJR).)

Published
2018
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15. Liver safety of non-tumour necrosis factor inhibitors in rheumatic patients with past hepatitis B virus infection: an observational, controlled, long-term study.

Author

Papalopoulos I, Fanouriakis A, Kougkas N, Flouri I, Sourvinos G, Bertsias G, Repa A, Avgoustidis N, and Sidiropoulos P

Subjects
Adult, Aged, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid immunology, Chemical and Drug Induced Liver Injury diagnosis, Female, Greece, Hepatitis B diagnosis, Hepatitis B immunology, Hepatitis B virus immunology, Humans, Immunocompromised Host, Male, Middle Aged, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha immunology, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid drug therapy, Biological Products adverse effects, Chemical and Drug Induced Liver Injury etiology, Hepatitis B virology, Hepatitis B virus pathogenicity, Virus Activation
Abstract

Objectives: The risk of hepatitis B virus (HBV) reactivation with non-tumour necrosis factor inhibitor (non-TNFi) biologic agents in patients with rheumatic diseases and past HBV infection has not been definively elucidated. We assessed the comparative safety of non-TNFi and TNFi biologic agents in such patients in real-life clinical settings., Metgods: We carried out a retrospective cohort study from the Department of Rheumatology, University Hospital of Heraklion. Patients who received abatacept (ABA), tocilizumab (TCZ) or rituximab (RTX) during the period 2003-2016 and were HbsAg(-), anti-HBc(+), anti-HBs(±) at baseline, were monitored for HBV reactivation. Patients treated with TNFi agents during the same period were used as a control group., Results: 101 cases of non-TNFi (39 ABA, 32 RTX and 30 TCZ) and 111 cases of TNFi treatment were identified. In non-TNFi, 76 cases (75.2%) were anti-HBc(+)/anti-HBs(+) and 25 (24.8%) were anti-HBc(+)/anti-HBs(-), as compared to 82 (73.9%) and 29 (26.1%) in TNFi-treated, respectively. After a median (IQR) observation of 24.0 (34.7) months, two cases (2.0%) of HBV reactivation were identified in the non-TNFi group; one with ABA, successfully treated with entecavir, and one fatal case with RTX and prior exposure to cyclophosphamide. No reactivation was observed in the TNFi group (p=0.226 vs. non-TNFi). Αnti-HBs titres were significantly reduced compared to baseline in the non-TNFi group [median (IQR) 203.9 (954.7) mIU/ml before treatment versus 144.9 (962.9) mIU/ml after treatment, p=0.03]., Conclusions: Two cases of HBV reactivation highlight the risk for this complication in patients with past HBV infection under biologic therapy.

Published
2018

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