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1. Evaluation of serum interleukin-6 level as a surrogate marker of synovial inflammation and as a factor of structural progression in early rheumatoid arthritis: results from a French national multicenter cohort

Author

Baillet, Athan, Gossec, Laure, Paternotte, Simon, Etcheto, Adrien, Combe, Bernard, Meyer, Olivier, Mariette, Xavier, Gottenberg, Jacques-Eric, Dougados, Maxime, Saraux, Alain, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Hôpital Bichat, AP-HP, Service de rhumatologie, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Investigation Clinique INSERM 1412 ( CIC 1412 - BREST ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre d'Investigation Clinique INSERM 1412 (CIC 1412 - BREST), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)

Subjects
Male, MESH: Synovitis, [SDV]Life Sciences [q-bio], Arthritis, Rheumatoid, Cohort Studies, MESH : Female, Longitudinal Studies, MESH : Biomarkers, MESH: Longitudinal Studies, MESH: Cohort Studies, Ultrasonography, MESH : Longitudinal Studies, MESH : Synovitis, MESH : Ultrasonography, MESH: Arthritis, Rheumatoid, Synovitis, MESH: Middle Aged, MESH: Follow-Up Studies, Middle Aged, MESH : Adult, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Disease Progression, Female, MESH: Disease Progression, France, Adult, MESH : Interleukin-6, MESH : Male, MESH : Cohort Studies, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Humans, MESH : Middle Aged, MESH : France, MESH: Humans, [ SDV ] Life Sciences [q-bio], Interleukin-6, MESH : Humans, MESH : Follow-Up Studies, MESH: Adult, MESH : Disease Progression, MESH: Interleukin-6, MESH: Male, MESH: France, MESH : Arthritis, Rheumatoid, MESH: Biomarkers, MESH: Female, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Follow-Up Studies, MESH: Ultrasonography
Abstract

International audience; Objective: Interleukin-6 (IL-6) is a key cytokine in rheumatoid arthritis pathogenesis. We aimed to analyze the association between IL-6 serum levels and joint inflammation at baseline and the correlation of time-integrated IL-6 values with structural damage during the first 36 months of early arthritis.Methods: IL-6 was assessed by 2 different methods in 813 patients of the French early arthritis cohort ESPOIR (Etude et Suivi des Polyarthrites Indifférenciées Récentes) over 36 months. IL-6 and C-reactive protein (CRP) changes were correlated to radiographic progression assessed by the total Sharp/van der Heijde score (SHS). Synovium inflammation was assessed in a subgroup of 126 patients by ultrasonography (US). The relationship between SHS change and IL-6 or CRP levels at baseline was investigated by a univariate regression and a multivariable analysis. A longitudinal model nested by visit and patient was conducted to assess the role of IL-6 on SHS at each visit.Results: At baseline, IL-6 was more strongly correlated with the swollen joint count than CRP level. In the univariate analysis, the time-integrated value of IL-6 was more strongly correlated with the swollen joint count and the variation of SHS than time-integrated CRP level. Baseline IL-6 was not independently associated with SHS change. Longitudinal models nested by patient showed that IL-6 levels were associated with structural damage independently from the Disease Activity Score in 28 joints, smoking status, rheumatoid factor, and anti-citrullinated protein peptide antibody serology, treatments, and CRP levels.Conclusion: IL-6 level was a marker of US synovitis at baseline. Repeated measurements of IL-6 are associated with structural damage.

Published
2015
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2. Improving agreement in assessment of synovitis in rheumatoid arthritis

Author

Peter P. Cheung, Emmanuel Chatelus, François Pouyol, Adeline Ruyssen-Witrand, Laure Gossec, Mélanie Gilson, Sandrine Guis, Martin Soubrier, Nathalie Balandraud, Thierry Marhadour, Pascal Richette, Ghislaine Gill, Isabelle Chary-Valckenaere, Stephan Pavy, Emmanuelle Dernis, Vincent André, Gérard Chalès, Gaël Mouterde, Maxime Dougados, National University Health System, Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Centre Hospitalier du Mans, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), CHU Pontchaillou [Rennes], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Rhumatologie, Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie, Service de rhumatologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Roger Salengro, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AP-HP, pôle appareil locomoteur, Service de rhumatologie, Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Gabriel Montpied (CHU), CHU Clermont-Ferrand, National University Health System [Singapore] (NUHS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Roger Salengro [Lille], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Gabriel Montpied [Clermont-Ferrand], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Ingénierie Moléculaire et Physiopathologie Articulaire ( IMoPA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Centre de résonance magnétique biologique et médicale ( CRMBM ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) -Centre National de la Recherche Scientifique ( CNRS ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), and CHU Gabriel Montpied ( CHU )

Subjects
Male, MESH: Synovitis, MESH : Aged, Arthritis, MESH: Observer Variation, Severity of Illness Index, MESH : Consensus, Arthritis, Rheumatoid, MESH : Cross-Sectional Studies, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 0302 clinical medicine, Medicine, MESH : Female, 030212 general & internal medicine, skin and connective tissue diseases, MESH : Joints, MESH : Synovitis, Observer Variation, MESH: Aged, MESH: Arthritis, Rheumatoid, Synovitis, MESH: Middle Aged, medicine.diagnostic_test, Swollen joints, MESH : Adult, Middle Aged, 3. Good health, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Reproducibility of Results, MESH: Joints, Rheumatoid arthritis, MESH : Severity of Illness Index, Female, Clinical Competence, MESH: Clinical Competence, Clinical competence, Adult, musculoskeletal diseases, medicine.medical_specialty, Validation study, Consensus, MESH : Male, Physical examination, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, MESH: Cross-Sectional Studies, Rheumatology, MESH: Rheumatology, MESH: Severity of Illness Index, Humans, MESH : Middle Aged, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Consensus, MESH : Rheumatology, Aged, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Reproducibility of Results, MESH : Humans, Reproducibility of Results, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH : Observer Variation, medicine.disease, MESH : Clinical Competence, MESH: Male, Cross-Sectional Studies, MESH : Arthritis, Rheumatoid, Physical therapy, Joints, Treatment decision making, business, MESH: Female
Abstract

International audience; Synovitis assessment through evaluation of swollen joints is integral in steering treatment decisions in rheumatoid arthritis (RA). However, there is high inter-observer variation. The objective was to assess if a short collegiate consensus would improve swollen joint agreement between rheumatologists and whether this was affected by experience.; Eighteen rheumatologists from French university rheumatology units participated in three 30 minutes rounds over a half day meeting evaluating joint counts of RA patients in small groups, followed by short consensus discussions. Agreement was evaluated at the end of each round as follows: (i) global agreement of swollen joints (ii) swollen joint agreement according to level of experience of the rheumatologist (iii) swollen joint count and (iv) agreement of disease activity state according to the Disease Activity Score (DAS28). Agreement was calculated using percentage agreement and kappa.; Global agreement of swollen joints failed to improve (kappa 0.50 to 0.52) at the joint level. Agreement between seniors did not improve but agreement between newly qualified rheumatologists and their senior peer, which was initially poor (kappa 0.28), improved significantly (to 0.54) at the end of the consensus exercises. Concordance of DAS28 activity states improved from 71% to 87%.; Consensus exercises for swollen joint assessment is worthwhile and may potentially improve agreement between clinicians in clinical synovitis and disease activity state, benefit was mostly observed in newly qualified rheumatologists.

Published
2013
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3. Evidence of the symptomatic and structural efficacy of methotrexate in daily practice as the first disease-modifying drug in rheumatoid arthritis despite its suboptimal use: results from the ESPOIR early synovitis cohort

Author

Gaujoux-Viala, Cécile, Paternotte, Simon, Combe, Bernard, Dougados, Maxime, Saraux, Alain, Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre d'Investigation Clinique ( CIC - Brest ), and Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, MESH: Antirheumatic Agents, MESH: Synovitis, Health Status, MESH : Aged, Arthritis, MESH : Dose-Response Relationship, Drug, Severity of Illness Index, Gastroenterology, MESH: Dose-Response Relationship, Drug, Arthritis, Rheumatoid, Cohort Studies, 0302 clinical medicine, Outcome Assessment, Health Care, Pharmacology (medical), MESH : Female, 030212 general & internal medicine, skin and connective tissue diseases, MESH: Cohort Studies, MESH: Health Status, media_common, MESH: Treatment Outcome, MESH : Synovitis, MESH: Aged, MESH: Arthritis, Rheumatoid, Synovitis, MESH: Middle Aged, Middle Aged, MESH : Adult, MESH : Antirheumatic Agents, 3. Good health, Treatment Outcome, MESH: Methotrexate, MESH: Young Adult, Antirheumatic Agents, Rheumatoid arthritis, Cohort, Disease Progression, Drug Therapy, Combination, Female, MESH : Severity of Illness Index, MESH: Disease Progression, medicine.drug, Adult, Drug, musculoskeletal diseases, medicine.medical_specialty, Adolescent, MESH : Outcome Assessment (Health Care), media_common.quotation_subject, MESH : Male, MESH : Young Adult, MESH : Cohort Studies, MESH : Treatment Outcome, MESH: Folic Acid, Young Adult, 03 medical and health sciences, Folic Acid, Rheumatology, Internal medicine, MESH : Adolescent, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Severity of Illness Index, medicine, Humans, MESH : Middle Aged, MESH : Health Status, MESH: Outcome Assessment (Health Care), Aged, 030203 arthritis & rheumatology, MESH: Adolescent, MESH : Folic Acid, MESH: Humans, Dose-Response Relationship, Drug, business.industry, MESH : Drug Therapy, Combination, MESH : Humans, MESH: Adult, MESH : Disease Progression, medicine.disease, MESH: Male, Surgery, MESH: Drug Therapy, Combination, Methotrexate, Concomitant, MESH : Methotrexate, Propensity score matching, MESH : Arthritis, Rheumatoid, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; OBJECTIVE: To describe the use of MTX in early arthritis (EA) in daily clinical practice and to evaluate its 6-month symptomatic efficacy and 12-month structural efficacy. METHODS: Patients included in the French observational ESPOIR cohort were assessed. Evaluation of the symptomatic and structural efficacy was performed by generalized linear regression after adjustment on propensity score (PS) in the group of patients receiving at least 3 months of MTX vs the ones receiving any other treatment except LEF, SSZ or TNF inhibitors. RESULTS: Within the first 6 months of follow-up of 777 EA patients, 59% received a DMARD, which was MTX in 68% (N = 313) of patients. The mean dose of MTX was 12.7 ± 3.8 mg/week. Only 53.7% of the patients received folic acid supplementation. MTX was initiated in patients with more active and severe disease. At 6 months, in unadjusted analysis, patients starting MTX had a significantly higher DAS-28 (3.58 vs 3.23; P = 0.001) and a significantly higher HAQ (0.60 vs. 0.48; P = 0.01) compared with controls. After adjustment by PS, there were no significant differences. Adjustment for the PS also revealed a statistically significant decrease in the radiological progression at 12 months in the MTX group [total Sharp-van der Heijde score (SHS), 1.05 ± 0.29 vs 2.02 ± 0.29, P = 0.025]. CONCLUSION: This study confirms the symptomatic and structural efficacy of MTX in EA in daily practice despite the non-optimal use of MTX, including low doses and infrequent concomitant folic acid supplementation.

Published
2012
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4. 2010 Rheumatoid Arthritis Classification Criteria An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

Author

Aletaha, Daniel, Neogi, Tuhina, Silman, J., Funovits, Julia, Felson, David T, Bingham, Clifton O, Birnbaum, Neal S, Burmester, Gerd R, Bykerk, P., Combe, Bernard, Costenbader, Karen H, Dougados, Maxime, Emery, Paul P, Ferraccioli, Gianfranco, Hazes, Johanna M W, Hobbs, Kathryn, Huizinga, Tom W J, Kavanaugh, Arthur, Kay, Jonathan, Kvien, Tore K, Laing, Timothy, Mease, Philip, Menard, H. A., Moreland, Larry W, Naden, Raymond L, Pincus, Theodore, Smolen, Josef S, Stanislawska-Biernat, Ewa, Symmons, Deborah, Tak, Paul P, Upchurch, Katherine S, Vencovsky, Jirí, Wolfe, Frederick, Hawker, Gillian, Silman, Alan J, Bykerk, Vivian P, Cohen, Marc D, Ménard, Henri A, Saraux, A., AII - Amsterdam institute for Infection and Immunity, Clinical Immunology and Rheumatology, Tufts University School of Medicine [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Service de rhumatologie [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Leeds, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Leiden University Medical Center (LUMC), Virginia Tech [Blacksburg], University of Colorado [Boulder], Department of Rheumatology, Diakonhjemmet Hospital, CHU Pontchaillou [Rennes], Division of Rheumatology (NYU Hospital - Rheumato), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU)-NYU System (NYU), Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, University of Amsterdam [Amsterdam] (UvA), Institute of Rheumatology, Institut de Neurosciences de la Timone (INT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), ARC Epidemiology Unit, The University of Manchester, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique INSERM 1412 (CIC 1412 - BREST), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rheumatology, Faculteit der Geneeskunde, The University of North Carolina at Chapel Hill, Charité - University Medicine, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Recherche Agronomique ( INRA ), Service de Rhumatologie [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Erasmus MC, University Medical Center Rotterdam, Hogeschool Rotterdam, University of Colorado Boulder [Boulder], Division of Rheumatology ( NYU Hospital - Rheumato ), New York University Hospital, University of Amsterdam [Amsterdam] ( UvA ), Institut de Neurosciences de la Timone ( INT ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Lymphocyte B et Auto-immunité ( LBAI ), Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHRU Brest - Service de Rhumatologie ( CHU - BREST - Rhumato ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Centre d'Investigation Clinique INSERM 1412 ( CIC 1412 - BREST ), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Universiteit Leiden, Medizinische Universität Wien = Medical University of Vienna, Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
Time Factors, MESH : International Cooperation, MESH: Synovitis, International Cooperation, [SDV]Life Sciences [q-bio], Arthritis, Disease, Severity of Illness Index, MESH : Early Diagnosis, Arthritis, Rheumatoid, MESH : North America, MESH: Early Diagnosis, MESH: Acute-Phase Reaction, Immunology and Allergy, Pharmacology (medical), MESH : Algorithms, Societies, Medical, MESH : Synovitis, MESH: Arthritis, Rheumatoid, Synovitis, biology, undifferentiated arthritis citrullinated peptide controlled-trial methotrexate disease progression antibodies therapies erosions, Anti–citrullinated protein antibody, Early Inflammatory Arthritis, Connective tissue disease, Europe, Rheumatoid arthritis, MESH : Severity of Illness Index, Algorithms, MESH : Time Factors, medicine.medical_specialty, MESH: Terminology as Topic, MESH : Europe, Immunology, MESH: Societies, Medical, MESH: Algorithms, MESH : Acute-Phase Reaction, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Terminology as Topic, Internal medicine, MESH: Severity of Illness Index, Severity of illness, medicine, MESH : Societies, Medical, Humans, Acute-Phase Reaction, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH: Time Factors, medicine.disease, MESH : Terminology as Topic, MESH: North America, MESH: International Cooperation, Early Diagnosis, MESH : Arthritis, Rheumatoid, North America, Physical therapy, biology.protein, MESH: Europe, business, Rheumatism
Abstract

Objective. The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease-this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." Results. In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). Conclusion. This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."

Published
2010
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5. Reproducibility of joint swelling assessment by sonography in patients with long-lasting rheumatoid arthritis (SEA-Repro study part II)

Author

Christophe Hudry, Jérémie Sellam, Maxime Dougados, M.A. D'Agostino, F. Etchepare, Cécile Hacquard, Isabelle Chary Valckenaere, Gérard Chalès, Jean David Albert, Sandrine Jousse-Joulin, Laurent Grange, Alain Saraux, Thierry Marhadour, Jacques Bentin, Damien Loeuille, Philippe Gaudin, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de Rhumatologie, CHU Brugmann, CHU Brugmann, Belgium, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Service de rhumatologie, Hôpital Sud, Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Physiopathologie, Pharmacologie et Ingénierie articulaires ( PPIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]

Subjects
Male, Settore MED/16 - REUMATOLOGIA, MESH: Synovitis, MESH : Aged, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, Cohen's kappa, Rheumatoid, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, 030212 general & internal medicine, Disease activity, MESH : Joints, Ultrasonography, MESH : Synovitis, MESH: Aged, MESH: Arthritis, Rheumatoid, Synovitis, MESH: Middle Aged, medicine.diagnostic_test, Doppler, Middle Aged, Reference Standards, MESH : Ultrasonography, Doppler, MESH: Reproducibility of Results, MESH: Joints, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Severity of Illness Index, Female, MESH: Reference Standards, Long lasting, medicine.medical_specialty, MESH : Male, Immunology, Physical examination, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, Ultrasound, medicine, Humans, In patient, MESH : Middle Aged, Aged, 030203 arthritis & rheumatology, Reproducibility, MESH: Humans, business.industry, MESH : Reproducibility of Results, Arthritis, MESH : Humans, Reproducibility of Results, Ultrasonography, Doppler, medicine.disease, MESH: Male, Surgery, Sonographer, MESH : Arthritis, Rheumatoid, MESH : Reference Standards, MESH: Ultrasonography, Doppler, Joints, Nuclear medicine, business, MESH: Female
Abstract

Objective.To evaluate the intraobserver and interobserver reproducibility of B-mode and power Doppler (PD) sonography in patients with active long-standing rheumatoid arthritis (RA) comparatively with clinical data.Methods.In each of 7 patients being considered for a change in their RA treatment regimen, 7 healthcare professionals examined the 28 joints used in the Disease Activity Score 28-joint count (DAS28). Then 7 sonographers examined each of the 7 patients twice, using previously published B-mode and PD grading systems. The clinical reference standard was presence of synovitis according to at least 4/7 examiners. The sonographic reference standard was at least grade 1 (ALG1) or 2 (ALG2) synovitis according to at least 4/7 sonographers. Interobserver reproducibility of sonography was assessed versus the sonographer having the best intraobserver reproducibility. Agreement was measured by Cohen’s kappa statistic.Results.Intraobserver and interobserver reproducibility of B-mode and PD used separately was fair to good. Agreement between clinicians and sonographers at all sites using B-mode, PD, and both was 0.46, 0.37, and 0.36, respectively, for grade 1 synovitis; and 0.58, 0.19, and 0.19 for grade 2 synovitis. The number of joints with synovitis was smaller by physical examination (36.7%) than by B-mode with ALG1 (58.6%; p < 0.001). The number of joints with synovitis was higher by physical examination than by PD with both ALG1 (17.8%; p < 0.0001) and ALG2 (6.6%; p < 0.0001).Conclusion.PD findings explain most of the difference between clinical and sonographic joint assessments for synovitis in patients with long-standing RA.

Published
2010
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6. Reproducibility of joint swelling assessments in long-lasting rheumatoid arthritis: Influence on disease activity score-28 values (SEA-repro study part I)

Author

Laurent Grange, Jean-David Albert, Christophe Hudry, Jérémie Sellam, F. Etchepare, Cécile Hacquard, Sandrine Jousse-Joulin, M.A. D'Agostino, Maxime Dougados, Thierry Marhadour, Alain Saraux, Philippe Gaudin, Gérard Chalès, Isabelle Chary Valckenaere, Jacques Bentin, Damien Loeuille, Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Physiopathologie, Pharmacologie et Ingénierie articulaires (PPIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, CHU Brugmann, CHU Brugmann, Belgium, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, Hôpital Sud, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Rhumatologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Physiopathologie, Pharmacologie et Ingénierie articulaires ( PPIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), and Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Male, Settore MED/16 - REUMATOLOGIA, MESH: Synovitis, MESH : Aged, Arthritis, Severity of Illness Index, Arthritis, Rheumatoid, 0302 clinical medicine, Cohen's kappa, Rheumatoid, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, MESH : Female, MESH : Joints, Ultrasonography, MESH : Synovitis, MESH: Aged, MESH: Arthritis, Rheumatoid, MESH: Middle Aged, Synovitis, Disease activity score-28, Technician, Middle Aged, Reference Standards, Reproducibility, MESH: Reproducibility of Results, MESH: Joints, Rheumatoid arthritis, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Severity of Illness Index, MESH: Reference Standards, Female, musculoskeletal diseases, medicine.medical_specialty, MESH : Male, Immunology, Rheumatoid Arthritis, Disease activity, 03 medical and health sciences, Rheumatology, MESH: Severity of Illness Index, Severity of illness, medicine, Humans, MESH : Middle Aged, Joint swelling, Aged, 030203 arthritis & rheumatology, MESH: Humans, business.industry, MESH : Reproducibility of Results, MESH : Humans, Reproducibility of Results, medicine.disease, MESH: Male, MESH : Reference Standards, MESH : Arthritis, Rheumatoid, Physical therapy, Joints, business, MESH: Female, 030215 immunology
Abstract

Objectives.To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score-28 (DAS28).Methods.Seven healthcare professionals from different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen’s kappa statistic.Results.Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively.Conclusion.Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone.

Published
2010
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