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1. Design of ANCHOR-RA: a multi-national cross-sectional study on screening for interstitial lung disease in patients with rheumatoid arthritis

Author

Jeffrey A. Sparks, Philippe Dieudé, Anna-Maria Hoffmann-Vold, Gerd R Burmester, Simon LF Walsh, Michael Kreuter, Christian Stock, Steven Sambevski, Margarida Alves, and Paul Emery

Subjects
Connective tissue diseases, Pulmonary fibrosis, Rheumatic diseases, Tomography, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Patients with rheumatoid arthritis (RA) are at risk of developing interstitial lung disease (ILD), which is associated with high mortality. Screening tools based on risk factors are needed to decide which patients with RA should be screened for ILD using high-resolution computed tomography (HRCT). The ANCHOR-RA study is a multi-national cross-sectional study that will develop a multivariable model for prediction of RA-ILD, which can be used to inform screening for RA-ILD in clinical practice. Methods Investigators will enrol consecutive patients with RA who have ≥ 2 of the following risk factors for RA-ILD: male; current or previous smoker; age ≥ 60 years at RA diagnosis; high-positive rheumatoid factor and/or anti-cyclic citrullinated peptide (titre > 3 x upper limit of normal); presence or history of certain extra-articular manifestations of RA (vasculitis, Felty’s syndrome, secondary Sjögren’s syndrome, cutaneous rheumatoid nodules, serositis, and/or scleritis/uveitis); high RA disease activity in the prior 12 months. Patients previously identified as having ILD, or who have had a CT scan in the prior 2 years, will not be eligible. Participants will undergo an HRCT scan at their local site, which will be assessed centrally by two expert radiologists. Data will be collected prospectively on demographic and RA-related characteristics, patient-reported outcomes, comorbidities and pulmonary function. The primary outcomes will be the development of a probability score for RA-ILD, based on a multivariable model incorporating potential risk factors commonly assessed in clinical practice, and an estimate of the prevalence of RA-ILD in the study population. It is planned that 1200 participants will be enrolled at approximately 30 sites in the USA, UK, Germany, France, Italy, Spain. Discussion Data from the ANCHOR-RA study will add to the body of evidence to support recommendations for screening for RA-ILD to improve detection of this important complication of RA and enable early intervention. Trial registration clinicaltrials.gov NCT05855109 (submission date: 3 May 2023).

Published
2024
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2. Osteoporosis and risk of fracture in heart transplant patients

Author

Marine Forien, Romain Coralli, Constance Verdonk, Sébastien Ottaviani, Esther Ebstein, Lucie Demaria, Elisabeth Palazzo, Richard Dorent, and Philippe Dieudé

Subjects
heart transplant, bone mineral density, fractures, osteoporosis, vertebral fracture (VF), Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

IntroductionSignificant bone loss occurs after heart transplantation, predominantly in the first year, with increased risk of incident fractures. The goal of this study was to evaluate the prevalence of fragility fractures in a population of heart transplantation patients and to identify the independent risk factors for fractures.MethodsThis was a prospective monocentric study that included patients with heart transplantation occurring < 10 years who were undergoing heart transplantation monitoring. All patients underwent bone mineral density evaluation by dual-energy X-ray absorptiometry and radiographies to establish the presence of vertebral fractures.ResultsWe included 79 patients (61 men); the mean age was 56.8 ± 10.8 years. The mean time between transplantation and inclusion was 32.3 ± 35.0 months. Incident fractures were diagnosed in 21 (27%) patients after heart transplantation. Vertebral fractures were the most frequent (30 vertebral fractures for 15 patients). Osteoporosis was confirmed in 22 (28%) patients. Mean bone mineral density at the femoral neck and total hip was lower with than without fracture (femoral neck: 0.777 ± 0.125 vs 0.892 ± 0.174 g/cm2, p

Published
2023
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4. Clinical features and outcomes of patients with myositis associated-interstitial lung disease

Author

Theodoros Karampitsakos, Vasilios Tzilas, Ourania Papaioannou, Serafeim Chrysikos, Eirini Vasarmidi, Pierre-Antoine Juge, Styliani Vizirianaki, Eleni Bibaki, Argyro Reppa, Prodromos Sidiropoulos, Matthaios Katsaras, Vasilina Sotiropoulou, Panagiota Tsiri, Electra Koulousousa, Eva Theochari, Georgios Tsirikos, Ioannis Christopoulos, Elli Malakounidou, Eirini Zarkadi, Fotios Sampsonas, Georgios Hillas, Theofanis Karageorgas, Dimitrios Daoussis, Christina Kalogeropoulou, Katerina Dimakou, Nikolaos Tzanakis, Raphael Borie, Philippe Dieudé, Katerina Antoniou, Bruno Crestani, Demosthenes Bouros, and Argyris Tzouvelekis

Subjects
myositis, interstitial lung disease, organizing pneumonia, amyopathic, survival, Medicine (General), R5-920
Abstract

IntroductionMyositis associated interstitial lung disease (ILD) seems to be an under-recognized entity.MethodsIn this multicenter, retrospective study, we recorded between 9/12/2019 and 30/9/2021 consecutive patients who presented in five different ILD centers from two European countries (Greece, France) and received a multidisciplinary diagnosis of myositis associated-ILD. The primary outcome was all-cause mortality over 1 year in specific subgroups of patients. Secondary outcomes included comparison of disease characteristics between patients diagnosed with the amyopathic subtype and patients with evidence of myopathy at diagnosis.ResultsWe identified 75 patients with myositis associated-ILD. Median age (95% CI) at the time of diagnosis was 64.0 (61.0–65.0) years. Antinuclear antibody testing was positive in 40% of the cohort (n = 30/75). Myopathy onset occurred first in 40.0% of cases (n = 30), ILD without evidence of myopathy occurred in 29 patients (38.7%), while 16 patients (21.3%) were diagnosed concomitantly with ILD and myopathy. The commonest radiographic pattern was cellular non-specific interstitial pneumonia (NSIP) and was observed in 29 patients (38.7%). The radiographic pattern of organizing pneumonia was significantly more common in patients diagnosed with the amyopathic subtype compared to patients that presented with myopathy [24.1% (n = 7/29) vs. 6.5% (n = 3/46), p = 0.03]. One year survival was 86.7% in the overall population. Kaplan–Meier analysis demonstrated significantly higher all-cause 1-year mortality in patients with the amyopathic subtype compared to patients with evidence of myopathy [H R 4.24 (95% CI: 1.16–15.54), p = 0.03]. Patients diagnosed following hospitalization due to acute respiratory failure experienced increased risk of 1-year all-cause mortality compared to patients diagnosed in outpatient setting [HR 6.70 (95% CI: 1.19–37.81), p = 0.03]. Finally, patients with positive anti-MDA5 presented with higher 1-year all-cause mortality compared to anti-MDA5 negative patients [HR 28.37 (95% CI: 5.13–157.01), p = 0.0001].ConclusionSpecific ILD radiographic patterns such as NSIP and organizing pneumonia may herald underlying inflammatory myopathies. Hospitalized patients presenting with bilateral organizing pneumonia refractory to antibiotics should be meticulously evaluated for myositis associated-ILD even if there is no overt muscular involvement. Incorporation of ILD radiological patterns in the diagnostic criteria of inflammatory myopathies may lead to timely therapeutic interventions and positively impact patients’ survival.

Published
2023
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5. Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort

Author

Gaël Mouterde, Nathalie Rincheval, Cédric Lukas, Claire Daien, Alain Saraux, Philippe Dieudé, Jacques Morel, and Bernard Combe

Subjects
Rheumatoid arthritis, Early arthritis, Seronegative arthritis, Arthritis, ESPOIR cohort, Anti-citrullinated protein antibodies (ACPA), Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Objective To describe the disease course of patients with early arthritis without rheumatoid factor (RF) and anti-citrullinated protein auto-antibodies (ACPA) in an inception cohort. To determine baseline predictors of fulfilling 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) for these patients within 3 years. Method Patients included in the multicenter ESPOIR cohort were compared at baseline and 3 years by whether they were negative for RF and ACPA (“seronegative”) or positive for RF and/or ACPA (“seropositive”). Univariate analysis was used to determine the association between baseline variables in seronegative patients and RA classification. Stepwise multiple logistic regression was used to identify predictors of RA classification within 3 years, estimating odds ratios (ORs). Results Among 354 seronegative patients, 224/340 with available data (65.9%) fulfilled RA classification at baseline and 189/233 (81.1%) at 3 years. As compared with seropositive patients, seronegative patients had lower DAS28 (p = 0.002) and lower modified total Sharp score (mTSS; p = 0.026) at baseline; DAS28 remission was similar (p = 0.634), but radiographic progression rate was lower in seronegative patients (p

Published
2019
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6. The genetics of interstitial lung diseases

Author

Raphael Borie, Pierre Le Guen, Mada Ghanem, Camille Taillé, Clairelyne Dupin, Philippe Dieudé, Caroline Kannengiesser, and Bruno Crestani

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Interstitial lung diseases (ILDs) are a set of heterogeneous lung diseases characterised by inflammation and, in some cases, fibrosis. These lung conditions lead to dyspnoea, cough, abnormalities in gas exchange, restrictive physiology (characterised by decreased lung volumes), hypoxaemia and, if progressive, respiratory failure. In some cases, ILDs can be caused by systemic diseases or environmental exposures. The ability to treat or cure these ILDs varies based on the subtype and in many cases lung transplantation remains the only curative therapy. There is a growing body of evidence that both common and rare genetic variants contribute to the development and clinical manifestation of many of the ILDs. Here, we review the current understanding of genetic risk and ILD.

Published
2019
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7. Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort.

Author

Gaetane Nocturne, Stephan Pavy, Saida Boudaoud, Raphaèle Seror, Philippe Goupille, Philippe Chanson, Désirée van der Heijde, Floris van Gaalen, Francis Berenbaum, Xavier Mariette, Karine Briot, Antoine Feydy, Pascal Claudepierre, Philippe Dieudé, Joanne Nithitham, Kimberly E Taylor, Lindsey A Criswell, Maxime Dougados, Christian Roux, and Corinne Miceli-Richard

Subjects
Medicine, Science
Abstract

To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and

Published
2015
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8. Which and How Many Patients Should Be Included in Randomised Controlled Trials to Demonstrate the Efficacy of Biologics in Primary Sjögren's Syndrome?

Author

Valérie Devauchelle-Pensec, Jacques-Eric Gottenberg, Sandrine Jousse-Joulin, Jean-Marie Berthelot, Aleth Perdriger, Eric Hachulla, Pierre Yves Hatron, Xavier Puechal, Véronique Le Guern, Jean Sibilia, Laurent Chiche, Vincent Goeb, Olivier Vittecoq, Claire Larroche, Anne Laure Fauchais, Gilles Hayem, Jacques Morel, Charles Zarnitsky, Jean Jacques Dubost, Philippe Dieudé, Jacques Olivier Pers, Divi Cornec, Raphaele Seror, Xavier Mariette, Emmanuel Nowak, and Alain Saraux

Subjects
Medicine, Science
Abstract

OBJECTIVE:The goal of this study was to determine how the choice of the primary endpoint influenced sample size estimates in randomised controlled trials (RCTs) of treatments for primary Sjögren's syndrome (pSS). METHODS:We reviewed all studies evaluating biotechnological therapies in pSS to identify their inclusion criteria and primary endpoints. Then, in a large cohort (ASSESS), we determined the proportion of patients who would be included in RCTs using various inclusion criteria sets. Finally, we used the population of a large randomised therapeutic trial in pSS (TEARS) to assess the impact of various primary objectives and endpoints on estimated sample sizes. These analyses were performed only for the endpoints indicating greater efficacy of rituximab compared to the placebo. RESULTS:We identified 18 studies. The most common inclusion criteria were short disease duration; systemic involvement; high mean visual analogue scale (VAS) scores for dryness, pain, and fatigue; and biological evidence of activity. In the ASSESS cohort, 35 percent of patients had recent-onset disease (lower than 4 years), 68 percent systemic manifestations, 68 percent high scores on two of three VASs, and 52 percent biological evidence of activity. The primary endpoints associated with the smallest sample sizes (nlower than 200) were a VAS dryness score improvement higher to 20 mm by week 24 or variable improvements (10, 20, or 30 mm) in fatigue VAS by week 6 or 16. For patients with systemic manifestations, the ESSDAI change may be the most logical endpoint, as it reflects all domains of disease activity. However, the ESSDAI did not improve significantly with rituximab therapy in the TEARS study. Ultrasound score improvement produced the smallest sample size estimate in the TEARS study. CONCLUSION:This study provides valuable information for designing future RCTs on the basis of previously published studies. Previous RCTs used inclusion criteria that selected a small part of the entire pSS population. The endpoint was usually based on VASs assessing patient complaints. In contrast to VAS dryness cut-offs, VAS fatigue cut-offs did not affect estimated sample sizes. SGUS improvement produced the smallest estimated sample size. Further studies are required to validate standardised SGUS modalities and assessment criteria. Thus, researchers should strive to develop a composite primary endpoint and to determine its best cut-off and assessment time point.

Published
2015
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9. Early-onset osteoarthritis, Charcot-Marie-Tooth like neuropathy, autoimmune features, multiple arterial aneurysms and dissections: an unrecognized and life threatening condition.

Author

Mélodie Aubart, Delphine Gobert, Fleur Aubart-Cohen, Delphine Detaint, Nadine Hanna, Hyacintha d'Indya, Janine-Sophie Lequintrec, Philippe Renard, Anne-Marie Vigneron, Philippe Dieudé, Jean-Pierre Laissy, Pierre Koch, Christine Muti, Joelle Roume, Veronica Cusin, Bernard Grandchamp, Laurent Gouya, Eric LeGuern, Thomas Papo, Catherine Boileau, and Guillaume Jondeau

Subjects
Medicine, Science
Abstract

BackgroundSevere osteoarthritis and thoracic aortic aneurysms have recently been associated with mutations in the SMAD3 gene, but the full clinical spectrum is incompletely defined.MethodsAll SMAD3 gene mutation carriers coming to our centre and their families were investigated prospectively with a structured panel including standardized clinical workup, blood tests, total body computed tomography, joint X-rays. Electroneuromyography was performed in selected cases.ResultsThirty-four SMAD3 gene mutation carriers coming to our centre were identified and 16 relatives were considered affected because of aortic surgery or sudden death (total 50 subjects). Aortic disease was present in 72%, complicated with aortic dissection, surgery or sudden death in 56% at a mean age of 45 years. Aneurysm or tortuosity of the neck arteries was present in 78%, other arteries were affected in 44%, including dissection of coronary artery. Overall, 95% of mutation carriers displayed either aortic or extra-aortic arterial disease. Acrocyanosis was also present in the majority of patients. Osteoarticular manifestations were recorded in all patients. Joint involvement could be severe requiring surgery in young patients, of unusual localization such as tarsus or shoulder, or mimicking crystalline arthropathy with fibrocartilage calcifications. Sixty eight percent of patients displayed neurological symptoms, and 9 suffered peripheral neuropathy. Electroneuromyography revealed an axonal motor and sensory neuropathy in 3 different families, very evocative of type II Charcot-Marie-Tooth (CMT2) disease, although none had mutations in the known CMT2 genes. Autoimmune features including Sjogren's disease, rheumatoid arthritis, Hashimoto's disease, or isolated autoantibodies- were found in 36% of patients.InterpretationSMAD3 gene mutations are associated with aortic dilatation and osteoarthritis, but also autoimmunity and peripheral neuropathy which mimics type II Charcot-Marie-Tooth.

Published
2014
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10. Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.

Author

Yukinori Okada, Dorothee Diogo, Jeffrey D Greenberg, Faten Mouassess, Walid A L Achkar, Robert S Fulton, Joshua C Denny, Namrata Gupta, Daniel Mirel, Stacy Gabriel, Gang Li, Joel M Kremer, Dimitrios A Pappas, Robert J Carroll, Anne E Eyler, Gosia Trynka, Eli A Stahl, Jing Cui, Richa Saxena, Marieke J H Coenen, Henk-Jan Guchelaar, Tom W J Huizinga, Philippe Dieudé, Xavier Mariette, Anne Barton, Helena Canhão, João E Fonseca, Niek de Vries, Paul P Tak, Larry W Moreland, S Louis Bridges, Corinne Miceli-Richard, Hyon K Choi, Yoichiro Kamatani, Pilar Galan, Mark Lathrop, Towfique Raj, Philip L De Jager, Soumya Raychaudhuri, Jane Worthington, Leonid Padyukov, Lars Klareskog, Katherine A Siminovitch, Peter K Gregersen, Elaine R Mardis, Thurayya Arayssi, Layla A Kazkaz, and Robert M Plenge

Subjects
Medicine, Science
Abstract

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

Published
2014
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11. Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans.

Author

Joanna E Cobb, Darren Plant, Edward Flynn, Meriem Tadjeddine, Philippe Dieudé, François Cornélis, Lisbeth Ärlestig, Solbritt Rantapää Dahlqvist, George Goulielmos, Dimitrios T Boumpas, Prodromos Sidiropoulos, Sophine B Krintel, Lykke M Ørnbjerg, Merete L Hetland, Lars Klareskog, Thomas Haeupl, Andrew Filer, Christopher D Buckley, Karim Raza, Torsten Witte, Reinhold E Schmidt, Oliver FitzGerald, Douglas Veale, Stephen Eyre, and Jane Worthington

Subjects
Medicine, Science
Abstract

ObjectivesGenome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA.MethodsA cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data.ResultsSignificant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10(-9)).ConclusionsThis study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.

Published
2013
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12. Epistatic interaction between BANK1 and BLK in rheumatoid arthritis: results from a large trans-ethnic meta-analysis.

Author

Emmanuelle Génin, Baptiste Coustet, Yannick Allanore, Ikue Ito, Maria Teruel, Arnaud Constantin, Thierry Schaeverbeke, Adeline Ruyssen-Witrand, Shigeto Tohma, Alain Cantagrel, Olivier Vittecoq, Thomas Barnetche, Xavier Le Loët, Patrice Fardellone, Hiroshi Furukawa, Olivier Meyer, Benjamin Fernández-Gutiérrez, Alejandro Balsa, Miguel A González-Gay, Gilles Chiocchia, Naoyuki Tsuchiya, Javier Martin, and Philippe Dieudé

Subjects
Medicine, Science
Abstract

BACKGROUND: BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility. PATIENTS AND METHODS: We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes. RESULTS: None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (P(interaction) = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04-1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02-1.21], P = 0.012). CONCLUSION: This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis.

Published
2013
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13. Genotype/phenotype analyses for 53 Crohn's disease associated genetic polymorphisms.

Author

Camille Jung, Jean-Frédéric Colombel, Marc Lemann, Laurent Beaugerie, Matthieu Allez, Jacques Cosnes, Gwenola Vernier-Massouille, Jean-Marc Gornet, Jean-Pierre Gendre, Jean-Pierre Cezard, Frank M Ruemmele, Dominique Turck, Françoise Merlin, Habib Zouali, Christian Libersa, Philippe Dieudé, Nadem Soufir, Gilles Thomas, and Jean-Pierre Hugot

Subjects
Medicine, Science
Abstract

Background & aimsRecent studies reported a role for more than 70 genes or loci in the susceptibility to Crohn's disease (CD). However, the impact of these associations in clinical practice remains to be defined. The aim of the study was to analyse the relationship between genotypes and phenotypes for the main 53 CD-associated polymorphisms.MethodA cohort of 798 CD patients with a median follow up of 7 years was recruited by tertiary adult and paediatric gastroenterological centres. A detailed phenotypic description of the disease was recorded, including clinical presentation, response to treatments and complications. The participants were genotyped for 53 CD-associated variants previously reported in the literature and correlations with clinical sub-phenotypes were searched for. A replication cohort consisting of 722 CD patients was used to further explore the putative associations.ResultsThe NOD2 rare variants were associated with an earlier age at diagnosis (p = 0.0001) and an ileal involvement (OR = 2.25[1.49-3.41] and 2.77 [1.71-4.50] for rs2066844 and rs2066847, respectively). Colonic lesions were positively associated with the risk alleles of IL23R rs11209026 (OR = 2.25 [1.13-4.51]) and 6q21 rs7746082 (OR = 1.60 [1.10-2.34] and negatively associated with the risk alleles of IRGM rs13361189 (OR = 0.29 [0.11-0.74]) and DEFB1 rs11362 (OR = 0.50 [0.30-0.80]). The ATG16L1 and IRGM variants were associated with a non-inflammatory behaviour (OR = 1.75 [1.22-2.53] and OR = 1.50 [1.04-2.16] respectively). However, these associations lost significance after multiple testing corrections. The protective effect of the IRGM risk allele on colonic lesions was the only association replicated in the second cohort (p = 0.03).ConclusionsIt is not recommended to genotype the studied polymorphisms in routine practice.

Published
2012
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14. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

Author

Yannick Allanore, Mohamad Saad, Philippe Dieudé, Jérôme Avouac, Jorg H W Distler, Philippe Amouyel, Marco Matucci-Cerinic, Gabriella Riemekasten, Paolo Airo, Inga Melchers, Eric Hachulla, Daniele Cusi, H-Erich Wichmann, Julien Wipff, Jean-Charles Lambert, Nicolas Hunzelmann, Kiet Tiev, Paola Caramaschi, Elisabeth Diot, Otylia Kowal-Bielecka, Gabriele Valentini, Luc Mouthon, László Czirják, Nemanja Damjanov, Erika Salvi, Costanza Conti, Martina Müller, Ulf Müller-Ladner, Valeria Riccieri, Barbara Ruiz, Jean-Luc Cracowski, Luc Letenneur, Anne Marie Dupuy, Oliver Meyer, André Kahan, Arnold Munnich, Catherine Boileau, and Maria Martinez

Subjects
Genetics, QH426-470
Abstract

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P

Published
2011
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15. Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study

Author

Grégoire Martin de Frémont, Nathalie Costedoat-Chalumeau, Estibaliz Lazaro, Rakiba Belkhir, Gaëlle Guettrot-Imbert, Nathalie Morel, Gaétane Nocturne, Anna Molto, Tiphaine Goulenok, Elisabeth Diot, Laurent Perard, Nicole Ferreira-Maldent, Maelle Le Besnerais, Nicolas Limal, Nihal Martis, Noémie Abisror, Odile Debouverie, Christophe Richez, Vincent Sobanski, François Maurier, Gaëtan Sauvetre, Hervé Levesque, Marie-Agnès Timsit, Nathalie Tieulié, Pauline Orquevaux, Boris Bienvenu, Matthieu Mahevas, Thomas Papo, Céline Lartigau-Roussin, Elodie Chauvet, Emilie Berthoux, Françoise Sarrot-Reynauld, Loïc Raffray, Marion Couderc, Nicolas Martin Silva, Noémie Jourde-Chiche, Nicolas Belhomme, Thierry Thomas, Vincent Poindron, Viviane Queyrel-Moranne, Juliette Delforge, Camille Le Ray, Emmanuelle Pannier, Xavier Mariette, Véronique Le Guern, Raphaèle Seror, Alexandra AUDEMARD-VERGER, Emmanuel AZZI, Béatrice BANNEVILLE, Antoine BAUDET, Constance BEAUDOUIN BAZIRE, Cristina BELIZNA, Alexandre Belot, Ygal BENHAMOU, Alice Berezné, Fanny BERNARD-GUERVILLY, Sabine BERTHIER, Holy BEZANAHARY, Lisa BIALE, Adrien BIGOT, Claire BLANCHARD-DELAUNAY, Anne CALAS, Julien CAMPAGNE, Pascal CATHEBRAS, Claire CAZALETS, Benjamin CHAIGNE, Olivia CHANDESRIS, Jérémy CHATELAIS, Emmanuel CHATELUS, Fleur COHEN, Bernard Combe, Céline COMPARON, Pascal COQUERELLE, Louise DAMIAN, Eric DAUGAS, Mathilde DE MENTHON, Claire DE MOREUIL, Estelle DELATTRE, Azeddine DELLAL, Catherine Deneux-Tharaux, Amélie DENIS, Camille DEPROUW, Emmanuelle DERNIS, Alban DEROUX, Sandra DESOUCHES, Philippe Dieudé, Guillaume DIREZ, Maxime Dougados, Marine DRIESSEN, Aurélie DU THANH, Laetitia DUNOGEANT, Cécile DURANT, Cécile-Audrey DUREL, Isabelle DURIEU, Florence EBOUE, Elisabeth Elefant, Olivier FAIN, Bruno FAUTREL, René-Marc FLIPO, Aline FRAZIER, Antoine FROISSART, Sophie GEORGIN-LAVIALLE, Elisabeth GERVAIS, Bertrand GODEAU, François Goffinet, Anne GOMPEL, Laure GOSSEC, Philippe GOUPILLE, Claire GRANGE, Constance GUILLAUD-DANIS, Eric HACHULLA, Sabine HOEFSLOOT, Aurélie HUMMEL, Patrick JEGO, Stéphanie JOBARD, Laurence JOSSELIN-MAHR, Marc LAMBERT, Vincent LANGLOIS, Delphine LARIVIERE, Claire LARROCHE, Augustin LATOURTE, Christian LAVIGNE, Thomas LE GALLOU, Gaëlle LEROUX, Jean Guillaume LETAROUILLY, Frédéric LIOTÉ, Laurence Loeuillet, Jonathan London, Valentine Loustau, Pierre LOZAC'H, Emmanuel MAHEU, Hélène MAILLARD, Hubert MAROTTE, Agathe MASSEAU, Arsène MEKINIAN, Sara Melboucy Belkhir, Corinne Miceli-Richard, Martin MICHAUD, Marc MICHEL, Olivier MORANNE, Chafika MORATI-HAFSAOUI, Guillaume MOULIS, Luc MOUTHON, Barbara NICOLAS, Jacky Nizard, Jérémy ORA, Rodérau OUTH, Elisabeth PASQUIER, Jean-Loup PENNAFORTE, Antoinette PERLAT, Hélène PETIT-BAUER, Evangeline PILLEBOUT, Jean-Maxime PIOT, Agnès PORTIER, Olivier Pourrat, Xavier PUECHAL, Gregory PUGNET, Manon REDONDIN, Alexis REGENT, Mélanie RORIZ, Laurent SAILLER, Léa SAVEY, Marc SCHERLINGER, Nicolas SCHLEINITZ, Jérémie Sellam, Loïc Sentilhes, Aude SERVAIS, Perrine SMETS, Christelle SORDET, Martin SOUBRIER, Katia STANKOVIC-STOJANOVIC, Geoffrey URBANSKI, Véronique VEIT, Emmanuelle WEBER, and Cécile YELNIK

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2023
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16. Characterisation of a high-risk profile for maternal thrombotic and severe haemorrhagic complications in pregnant women with antiphospholipid syndrome in France (GR2): a multicentre, prospective, observational study

Author

Anne Murarasu, Gaëlle Guettrot-Imbert, Véronique Le Guern, Cécile Yelnik, Viviane Queyrel, Nicolas Schleinitz, Nicole Ferreira-Maldent, Elisabeth Diot, Geoffrey Urbanski, Emmanuelle Pannier, Estibaliz Lazaro, Odile Souchaud-Debouverie, Pauline Orquevaux, Nicolas Belhomme, Nathalie Morel, Elodie Chauvet, François Maurier, Maëlle Le Besnerais, Noemie Abisror, Tiphaine Goulenok, Françoise Sarrot-Reynauld, Alban Deroux, Elisabeth Pasquier, Claire de Moreuil, Holy Bezanahary, Laurent Pérard, Nicolas Limal, Vincent Langlois, Anne Calas, Bertrand Godeau, Christian Lavigne, Eric Hachulla, Fleur Cohen, Ygal Benhamou, Loïc Raffray, Mathilde de Menthon, Nathalie Tieulié, Vincent Poindron, Luc Mouthon, Maddalena Larosa, Elisabeth Eléfant, Loic Sentilhes, Anna Molto, Catherine Deneux-Tharaux, Nathalie Costedoat-Chalumeau, Emmanuel Azzi, Béatrice Banneville, Antoine Baudet, Constance Beaudouin-Bazire, Cristina Belizna, Rakiba Belkhir, Alice Berezne, Emilie Berthoux, Sabine Berthier, Lisa Biale, Boris Bienvenu, Claire Blanchard-Delaunay, Pascal Cathebras, Claire Cazalets, Benjamin Chaigne, Olivia Chandesris, Jérémy Chatelais, Emmanuel Chatelus, Pascal Coquerelle, Marion Couderc, Juliette Delforge, Amélie Denis, Sandra Desouches, Philippe Dieudé, Guillaume Direz, Marine Driessen, Aurélie Du Thanh, Laetitia Dunogeant, Cécile Durant, Isabelle Durieu, Marc Fabre, Olivier Fain, René-Marc Flipo, Aline Frazier, Antoine Froissart, Sophie Georgin-Lavialle, Elisabeth Gervais, Anne Gompel, Laure Gossec, Phillipe Goupille, Claire Grange, Constance Guillaud-Danis, Aurélie Hummel, Moez Jallouli, Patrick Jego, Stéphane Jobard, Laurence Josselin-Mahr, Noémie Jourde-Chiche, Anne-Sophie Korganow, Marc Lambert, Delphine Lariviere, Claire Larroche, Céline Lartigau-Roussin, Augustin Latourte, Thomas Le Gallou, Gaëlle Leroux, Hervé Levesque, Frédéric Lioté, Jonathan London, Valentine Loustau, Emmanuel Maheu, Matthieu Mahevas, Hélène Maillard, Xavier Mariette, Hubert Marotte, Nicolas Martin-Silva, Nihal Martis, Agathe Masseau, Arsène Mekinian, Sara Melboucy-Belkhir, Martin Michaud, Marc Michel, Chafika Morati-Hafsaoui, Jacky Nizard, Jérémy Ora, Jean-Loup Pennaforte, Antoinette Perlat, Hélène Petit Bauer, Evangeline Pillebout, Jean-Maxime Piot, Agnès Portier, Gregory Pugnet, Manon Redondin, Alexis Regent, Christophe Richez, Mélanie Roriz, Laurent Sailler, Gaëtan Sauvêtre, Léa Savey, Vincent Sobanski, Christelle Sordet, Martin Soubrier, Katia Stankovic Stojanovic, Thierry Thomas, Marie-Agnès Timsit, and Vassilis Tsatsaris

Subjects
Rheumatology, Immunology, Immunology and Allergy
Published
2022
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17. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

Author

Kazuyoshi, Ishigaki, Saori, Sakaue, Chikashi, Terao, Yang, Luo, Kyuto, Sonehara, Kensuke, Yamaguchi, Tiffany, Amariuta, Chun Lai, Too, Vincent A, Laufer, Ian C, Scott, Sebastien, Viatte, Meiko, Takahashi, Koichiro, Ohmura, Akira, Murasawa, Motomu, Hashimoto, Hiromu, Ito, Mohammed, Hammoudeh, Samar Al, Emadi, Basel K, Masri, Hussein, Halabi, Humeira, Badsha, Imad W, Uthman, Xin, Wu, Li, Lin, Ting, Li, Darren, Plant, Anne, Barton, Gisela, Orozco, Suzanne M M, Verstappen, John, Bowes, Alexander J, MacGregor, Suguru, Honda, Masaru, Koido, Kohei, Tomizuka, Yoichiro, Kamatani, Hiroaki, Tanaka, Eiichi, Tanaka, Akari, Suzuki, Yuichi, Maeda, Kenichi, Yamamoto, Satoru, Miyawaki, Gang, Xie, Jinyi, Zhang, Christopher I, Amos, Edward, Keystone, Gertjan, Wolbink, Irene, van der Horst-Bruinsma, Jing, Cui, Katherine P, Liao, Robert J, Carroll, Hye-Soon, Lee, So-Young, Bang, Katherine A, Siminovitch, Niek, de Vries, Lars, Alfredsson, Solbritt, Rantapää-Dahlqvist, Elizabeth W, Karlson, Sang-Cheol, Bae, Robert P, Kimberly, Jeffrey C, Edberg, Xavier, Mariette, Tom, Huizinga, Philippe, Dieudé, Matthias, Schneider, Martin, Kerick, Joshua C, Denny, Koichi, Matsuda, Keitaro, Matsuo, Tsuneyo, Mimori, Fumihiko, Matsuda, Keishi, Fujio, Yoshiya, Tanaka, Atsushi, Kumanogoh, Matthew, Traylor, Cathryn M, Lewis, Stephen, Eyre, Huji, Xu, Richa, Saxena, Thurayya, Arayssi, Yuta, Kochi, Katsunori, Ikari, Masayoshi, Harigai, Peter K, Gregersen, Kazuhiko, Yamamoto, S, Louis Bridges, Leonid, Padyukov, Javier, Martin, Lars, Klareskog, Yukinori, Okada, Soumya, Raychaudhuri, AII - Inflammatory diseases, Experimental Immunology, Clinical Immunology and Rheumatology, Rheumatology, AMS - Musculoskeletal Health, and AMS - Tissue Function & Regeneration

Subjects
Arthritis, Rheumatoid, Asian People, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Genetics, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Article, Genome-Wide Association Study, Adaptor Proteins, Signal Transducing
Abstract

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 x 10(-8)), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA.

Published
2022
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18. A Risk Score to Detect Subclinical Rheumatoid Arthritis–Associated Interstitial Lung Disease

Author

Pierre‐Antoine Juge, Benjamin Granger, Marie‐Pierre Debray, Esther Ebstein, Fabienne Louis‐Sidney, Joanna Kedra, Tracy J. Doyle, Raphaël Borie, Arnaud Constantin, Bernard Combe, René‐Marc Flipo, Xavier Mariette, Olivier Vittecoq, Alain Saraux, Guillermo Carvajal‐Alegria, Jean Sibilia, Francis Berenbaum, Caroline Kannengiesser, Catherine Boileau, Jeffrey A. Sparks, Bruno Crestani, Bruno Fautrel, and Philippe Dieudé

Subjects
Male, Arthritis, Rheumatoid, Rheumatology, Risk Factors, Immunology, Humans, Immunology and Allergy, Female, Prospective Studies, Lung Diseases, Interstitial, Lung, Mucin-5B
Abstract

Patients at high risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) would benefit from being identified before the onset of respiratory symptoms; this can be done by screening patients with the use of chest high-resolution computed tomography (HRCT). Our objective was to develop and validate a risk score for patients who have subclinical RA-ILD.Our study included a discovery population and a replication population from 2 prospective RA cohorts (ESPOIR and TRANSLATE2, respectively) without pulmonary symptoms who had received chest HRCT scans. All patients were genotyped for MUC5B rs35705950. After multiple logistic regression, a risk score based on independent risk factors for subclinical RA-ILD was developed in the discovery population and tested for validation in the replication population.The discovery population included 163 patients with RA, and the replication population included 89 patients with RA. The prevalence of subclinical RA-ILD was 19.0% and 16.9%, respectively. In the discovery population, independent risk factors for subclinical RA-ILD were presence of the MUC5B rs35705950 T allele (odds ratio [OR] 3.74 [95% confidence interval (95% CI) 1.37, 10.39]), male sex (OR 3.93 [95% CI 1.40, 11.39]), older age at RA onset (for each year, OR 1.10 [95% CI 1.04, 1.16]), and increased mean Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (for each unit, OR 2.03 [95% CI 1.24, 3.42]). We developed and validated a derived risk score with receiver operating characteristic areas under the curve of 0.82 (95% CI 0.70-0.94) for the discovery population and 0.78 (95% CI 0.65-0.92) for the replication population. Excluding MUC5B rs35705950 from the model provided a lower goodness of fit (likelihood ratio test, P = 0.01).We developed and validated a risk score that could help identify patients at high risk of subclinical RA-ILD. Our findings support an important contribution of MUC5B rs35705950 to subclinical RA-ILD risk.

Published
2022
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19. Screening for spondyloarthritis in patients with inflammatory bowel diseases

Author

Sébastien Ottaviani, Xavier Tréton, Marine Forien, Romain Coralli, Astrid Dauchez, Carmen Stefanescu, Anne-Laure Pelletier, Hakim Becheur, Esther Ebstein, Yoram Bouhnik, and Philippe Dieudé

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Inflammatory bowel diseases (IBDs) can be associated with various musculoskeletal (IBD-MSK) manifestations that could be difficult to classify for gastroenterologists. We aimed to evaluate the characteristics of patients with IBD-MSK and the prevalence of spondyloarthritis (SpA). In this observational cross-sectional study, we included patients with IBD-MSK complaints (peripheral or back pain). All patients underwent a standardized rheumatology evaluation including clinical, biological and imaging evaluations (MRI of spine and sacroiliac joints and ultrasonography of enthesis). We included 183 IBD patients (60.7% women; median [interquartile range] age 45 [36-56] years); 159 (87%) had joint pain. In 43 (23.5%) and 25/175 (14.3%) patients, enthesis abnormalities were found on ultrasonography and sacroiliitis on MRI, respectively. SpA was diagnosed in 54 (29.5%) patients. IBD-related arthralgia and degenerative spine disease were diagnosed in 105 (57.4%) and 72 (39.3%) patients. Sixteen (29.6%) SpA patients initiated a new conventional synthetic disease modifying anti-rheumatic drug (DMARD). A biologic DMARD was initiated in 10 patients or changed in 3. More than half of IBD-MSK patients had IBD-related arthralgia, and about one-third had definite SpA. Ultrasonography of enthesis and systematic MRI of sacroiliac joints seem useful for SpA classification and differential diagnosis in these patients who often have musculoskeletal pain complaints. Therapeutics were changed in most patients, which highlights the need for a multidisciplinary approach for managing IBD with extra-intestinal symptoms.

Published
2022
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22. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Anatole Harrois, Florence Patin, Anaïs Razurel, Laure Allanic, Grégoire Martin de Frémont, Vincent Jachiet, Gonçalo Boleto, Eric D'Ortenzio, Xavier Mariette, Philippe Dieudé, Etienne Canouï, Z Julia, Nathalie Dournon, Jean-Sébastien Hulot, David Lebeaux, Eric Mariotte, Dorothee Vallois, Laurence Berard, Nicolas Gambier, Christiane Verny, Mathilde Le Marchand, Mitja Jevnikar, Jean-Jacques Mourad, Marjolaine Morgand, Bertrand Guidet, Alexandre Moores, Prissile Bakouboula, Frédéric Pène, Pascal Richette, Martine Meunier, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Mamadou Salif Cisse, Marie-Hélène Legros, Yann Nguyen, Damien Roux, Robin Deleris, Maxence Decavele, Patrice Cacoub, Isabelle Dusanter, Patricia Senet, Nassim Mahtal, Raphael Borie, Philippe Benoit, Blandine Denis, Luca Semerano, Sebastien Abad, Marie Dubert, Marie Lachatre, Marine Livrozet, Nathan Ebstein, Lakhdar Mameri, Adrien Michon, Olivier Sanchez, Aurélien Guffroy, Pierre Dupland, Jérôme Pacanowski, Yasmina Ferfar, Tassadit Hadjam, Anne-Marie Roques, Celine Comparon, Solaya Chalal, A Soria, Isabelle Lehir, Anne Gysembergh-Houal, Stéphanie Alary, Valérie Dejean, Elena Kiouris, Estelle Henry, Sophie Diemunsch, Jonathan London, Fanny Charbonnier, Alexandre Demoule, Louise Bondeelle, Samira Saleh-Mghir, Lise Bernard, Brigitte Sabatier, Anne Jacolot, Aurelie Sautereau, Pierre Faye, Benjamin Fournier, Noémie Abisror, Awa Ndiaye, Ruben Benainous, Damien Sène, Emmanuelle Sacco, Isabelle Debrix, Gabriel Nisand, Régis Peffault de Latour, Anne Sophie Korganow, Kévin Cardet, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Elena Fois, Jean-Benoit Arlet, Christine Broissand, Yaël Amara, Matheus Vieira, Sophie Caillat-Zucman, Madona Sakkal, Juliette Djadi-Prat, Jean-Louis Teboul, Hélène François, Stéphane Renaud, Sylviane Ravato, Alaki Thiemele, Gabrielle Archer, Alain Fourreau, David Boutboul, Arsène Mekinian, Antoine Gros, Morgane Faure, Anne Pattyn, Camille Petit-Hoang, Jessica Krause le Garrec, Antony Canellas, Jean-Michel Molina, Zakaria Ait Hamou, Eric Oksenhendler, Ilias Koumis, Marie-Aude Penet, Catherine Boussard, Vincent Fallet, Guillaume Geri, Loic Kassegne, Bernard Cholley, Lucie Biard, Elodie Perrodeau, Tomas Urbina, David Schmitz, johann Cailhol, Elise Morawiec, Audrey Phibel, Sophie Renet, Emmanuel Weiss, Faouzi Saliba, Kristina Beziriganyan, Abdellatif Tazi, Isabelle Peigney, Bertrand Dunogue, Rémy Gauzit, Damien Bergerot, Bob Heger, Ines Ben-Mabrouk, Jade Ghosn, Benjamin Planquette, Alexis Régent, François Weill, Yasmina Mekid, Rosa Da Silva, Victor Lancon, Marc Michel, Nadia Anguel, Anne Claire Desbois, François Danion, Brigitte Ranque, Mohamed Belloul, Nadège Lemarié, Amélie Cransac, Marine Nadal, Lalia Djaghout, Anne Tréhan, Samy Figueiredo, Hakim Meddah, Aurélie Clan Hew Wai, Julie Delemazure, Soraya Fellahi, Jacques-Eric Gottenberg, Matthieu Uzzan, Jean-Charles Duclos-Vallée, Tabassome Simon, Vanessa Rathouin, Yves Hansmann, Hélène Gros, Syllia Belazouz, Nathalie Marin, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Annabelle Stoclin, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Miguel Alejandro Vasquez-Ibarra, Isabelle Madeleine, Simon Valayer, Anne Adda, Marie-Thérèse Tremorin, Nicolas Meyer, Vixra Keo, Lara Zafrani, Caroline Semaille, Maxime Dougados, Olivier Olivier, Emeline Colomba, Florence Morin, Claire Rouzaud, Paul Michel Mertes, Claire Montlahuc, Anne Blanchard, Valérie Pourchet-Martinez, Constance Delaugerre, Nicolas Carlier, Jacques Cadranel, Nicolas Noel, Kahina Cheref, Bao Phung, Moez Jallouli, Ulrich Clarac, Marthe Rigal, Mireille Adda, Lionel Galicier, Fanny Domont, Lee S. Nguyen, Férial Berbour, Fanny Pommeret, Celine Dupré, Gaël Leprun, Jean-Luc Diehl, Laetitia Languille, Philippe Blanche, Abolfazl Mohebbi, Mathilde Noaillon, Olivier Collange, Paul Jaubert, Anne Daguenel-Nguyen, Sandrine Briois, Anne-Lise Pouliquen, Coralie Bloch Queyrat, Clément Jourdaine, Cédric Pierron, Geoffrey Rossi, Chloe McAvoy, Claire Courtin, Mathias Cornic, C Rioux, Christine Lemagner, Martin Dres, Emmanuelle Guillot, Marc Garnier, Safaa Nemlaghi, Guillaume Grailles, Yazdan Yazdanpanah, Veronique Joly, Thiziri Sadaoui, Marion Bouhris, Vincent Castelain, Muriel Fartoukh, Sébastien Cavelot, Sophie Ohlmann-Caillard, Valentina Isernia, Bruno Crestani, Thinhinane Bariz, Benjamin Chaigne, Emmanuel Andrès, Frédéric Blanc, Alain Wynckel, Louise-Laure Mariani, Yasmine Messaoudi, Naima Sguiouar, Amina Kebir, Asmaa Mamoune, Caroline Gaudefroy, Victoire De Lastours, Pierre Diemunsch, Etienne Lengliné, Claire Tantet, Julien Mayaux, Benjamin G. Chousterman, Arthur Pavot, Anne Rachline, Gwenaël Lorillon, Hassan Joumaa, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Fanny Defrancq, Véronique Vigna, Yves Cohen, Amira Benattia, Martin Siguier, Sophie Georgin-Lavialle, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Olivier Hermine, Mathieu Vautier, Florence Tubach, Marion Licois, Anaïs Codorniu, Fanny Alby-Laurent, Jérémie Zerbit, Aude Jacob, Benedicte Giroux-Leprieur, Carine Karachi, Laurent Cylly, Edouard Flamarion, Gladys Aratus, Charléne Jouve, Robin Dhote, Claire Davoine, Valentin Greigert, Gaelle Leroux, Cécile Kedzia, Guillaume Lefèvre, Catherine Metzger, Olivier Benveniste, Clairelyne Dupin, Marie-Alexandra Alyanakian, Mathieu Oberlin, Julien Poissy, Linda Gimeno, Adrien Contejean, Segolene Toquet, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Virginie Zarrouk, Cécile Yelnik, Mandy Nizard, Mourad Djadel, F-Xavier Lescure, Agnes Maurer, Geoffroy Liégeon, Arthur Neuschwander, Hélène Lafoeste, Gaëtan Deslée, Frédéric De Blay, Claire Pernin, Cloé Comarmond, Anne Hutt, Ridha Belilita, Laurence Lecomte, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Jean-Jacques Tudesq, Benjamin Terrier, Solène Fabre, Lelia Escaut, Eva Chatron, Emmanuelle Blin, Pauline Jouany, Sara Sambin, Chistophe Willekens, Nabil Raked, Jean-Simon Rech, Serge Bureau, Boris Bienvenu, Elisabeth Coupez, Tali-Anne Szwebel, Lydia Suarez, Chaouki Bouras, Kamyl Baghli, Emilia Stan, Valérie Camara-Clayette, Fanette Denies, Nathalie Menage, Paul Legendre, Axelle Fuentes, Oriane Puéchal, Charlotte Kaeuffer, Guillaume Becker, Clara Campos-Vega, Armand Mekontso-Dessaps, Pernelle Vauboin, Yurdagul Uzunhan, F Louni, Marie hélène Pari, Myriam Virlouvet, Nicolas Belaube, Hugues Cordel, Nathalie Chavarot, Olivier Sitbon, Jean-Daniel Lelievre, Matthieu Mahévas, Julie Smati, Olivier Clovet, Marc Bardou, Ada Clarke, Gilles Garcia, Anouk Walter-Petrich, Hala Semri, Vasco Honsel, Giovanna Melica, Pierre Mora, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Céline Verstuyft Verstuyft, Blandine Lehmann, Pascal Martel, Aida Zahrate-Ghoul, Karine Martin, Alexandre Bourgoin, Baptiste Duceau, Philippe Ravaud, Celine Wilpotte, Sylvie Le Gac, Michaël Darmont, Aurélie Durel Maurisse, Younes Keroumi, Aude Rigolet, Julie Chas, Pierre-Louis Tharaux, Caroline Morbieu, Valérie Paquet, Eric Vicaut, Pascaline Choinier, Samir Hamiria, Elsa Feredj, Frédéric Schlemmer, Gilles Pialoux, Zeina Louis, Marion Parisey, David Montani, Jean-Pierre Riveline, Jean-Marie Michot, Pascal Lim, Eliane Bertrand, Gaelle Clavere, Julie Jambon, Stéphane Brin, Saskia Flamand, Jeanne Meunier, Geoffroy Volle, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Caroline Hauw-Berlemont, Gabriel Baron, Jeremy Arzoine, Loren Soyez-Herkert, Maria Pereira, Antoine Parrot, Johanna Oziel, Carole Burger, Eric Noll, Paul Vermes, Jeanne Goupil de Bouille, Xavier Monnet, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Jean-Philippe Bastard, Younes El Amine, Timothee Bironne, Damien Vanhoye, Amine Ghembaza, Laure Berton, Yvon Ruch, Thomas Volpe, Thomas Gorget, Jaouad Benhida, Julien Saussereau, Elodie Issorat, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Laurène Deconinck, A. Dossier, Félix Ackermann, Greggory Ducrocq, Anne Bergeron, Laurence Annonay, Camille Knosp, Laurence Drouard, Adrien Joseph, Hilario Nunes, Hanane Fodil, Sabrine Ouamri, Belkacem Asselate, Julie Fillon, Dominique Dautel, Isabelle Brindele, Robin Charreteur, S Lariven, Elie Azoulay, Sami Kolta, Cédric Sublon, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Bruno Mourvillier, Ewa Kozaliewicz, Vincent Provitolo, Marie Lecronier, Julien Chabert, Matthieu Resche-Rigon, Stéphan Pavy, Naura Gamany, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Corinne Guerin, Pierre Tissieres, Nathalie Costedoat-Chalumeau, Nessima Yelles, Emmanuel Chatelus, Jean-Christophe Corvol, Luc Mouthon, Marie Gilbert, Matthieu Lemoine, Lucie Aunay, Candice Estellat, Laure Choupeaux, Dhiaa Meriem Hai, Bernard Goichot, Céline Louapre, Roza Rahli, Nathalie De Castro, Christian Richard, Malikhone Chansombat, Kamil Chitour, Joseph Emmerich, Elodie Drouet, Julien Pottecher, Eric Demonsant, Alexandra Beurton, Raphaël Porcher, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Pierre-Grégoire Guinot, Nicolas Champtiaux, Caroline Pradon, Annick Tibi, Julien Le Marec, Nawal Derridj, Mohamad Zaidan, Eric Marquis, Mickael Henriques, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Diane Le Pluart, Coralie Gernez, Yacine Boudali, Dimitri Fremont, Pierrick Le Borgne, Corinne Pernot, Mélanie Dehais, Claire Madelaine, Dominique Roulot, Georgina Maalouf, Constance Guillaud, Corine Nyanou, Karine Celli Lebras, Sophie Granville, Sabrina Brahmi, Catherine Le Bourlout, Hassan Tarhini, Asmaa Mabrouki, Hakim Tayebi, Sophie Ismael, Jonathan Marey, Sophie Bayer, Gabriel Steg, Antoine Fayol, Catherine Fauvaux, Delphine Feyeux, Côme Bureau, Alexandre Morel, Agathe Bounhiol, Alexandre Buffet, Souad Benarab, Luc Haudebourg, Pierre Le Guen, Damien Vimpere, Xavier Jaïs, Clotilde Le Tiec Le Tiec, Sophie Bulifon, Pélagie Thibaut, Alison Klasen, Claire Pacheco, Anne Godier, Marie Antignac, Domitille Molinari, Philippe Durand, Olivier Lambotte, Paul Henri Grisot, Anne Lise Jegu, Vincent Poindron, Ruxandra Burlacu, Denis Jesuthasan, Sarah Benghanem, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Sara Virolle, Léa Resmini, Liem Binh Luong Nguyen, Marie Matignon, Céline Leplay, and Claire Aguilar

Subjects
medicine.medical_specialty, business.industry, Immunology, Hazard ratio, Absolute risk reduction, Articles, medicine.disease, law.invention, Clinical trial, Pneumonia, Sarilumab, Rheumatology, Randomized controlled trial, law, Internal medicine, Cohort, medicine, Immunology and Allergy, Adverse effect, business
Abstract

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Published
2022
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23. Salivary gland ultrasonography in patients with connective tissue diseases: a multi-centre observational study

Author

Manon Lesturgie-Talarek, Julia Goossens, Sabryne Berkani, Marine Forien, Pierre-Antoine Juge, Esther Ebstein, Elisabeth Palazzo, Raphael Borie, Bruno Crestani, Philippe Dieudé, and Sébastien Ottaviani

Subjects
Sjogren's Syndrome, Rheumatology, Humans, Pharmacology (medical), Connective Tissue Diseases, Head, Salivary Glands, Ultrasonography
Abstract

Objective US of salivary glands (SGUS) is a non-invasive tool that allows for diagnosing primary SS (pSS) or secondary SS (sSS). However, little is known about the prevalence of US findings of SS in other CTDs. The aim of this multi-centre observational study was to evaluate, in CTD patients with or without SS, the prevalence of abnormal SGUS findings and the possible association of the findings with clinical or biological phenotypes. Methods B-Mode SGUS was performed by one operator blinded to clinical data. Each SG was semi-quantitatively rated on a scale from 0 to 4 according to the Jousse-Joulin score; a score ≥2 was considered pathological. Results Data for 194 patients were analysed (pSS, n = 30; sSS, n = 39; other CTDs, n = 77; controls, n = 48). SGUS findings were abnormal in 80%, 67%, 25% and 2% of patients, respectively. Independent of the underlying disease, age and sex, abnormal SGUS findings were significantly associated with presence of anti-SSA antibodies (P Conclusion Abnormal SGUS findings were associated with anti-SSA antibody positivity independent of the underlying disease. In SS patients, abnormal findings were associated with immunologic features and mouth involvement. Among CTD patients, SGUS changes may be associated with a particular immune profile.

Published
2021
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24. Current issues in rheumatoid arthritis-associated interstitial lung disease

Author

Philippe Dieudé, Paul Emery, and Clive Kelly

Subjects
medicine.medical_specialty, business.industry, Immunology, Psychological intervention, Interstitial lung disease, Disease, medicine.disease, Clinical trial, Increased risk, Rheumatology, Rheumatoid arthritis, Intervention (counseling), medicine, Immunology and Allergy, Intensive care medicine, business
Abstract

Summary Rheumatoid arthritis (RA) is associated with a ten-fold increased risk of interstitial lung disease (ILD). The presence of ILD in a patient with RA influences both prognosis and the choice of therapeutic intervention. Although there has been increasing awareness of the relevance of ILD to the outcome of patients with RA, there remains limited consensus around several important aspects of disease diagnosis and management. This Review emphasises two of the main areas in which a much greater standardisation of approach is urgently needed. First, the development of a screening approach based on established risk factors is a priority. Learning how to identify patients with RA-associated ILD early and then monitoring their condition to assess progression and measure the potential influence of therapeutic interventions is essential. Second, there is a need to consolidate the therapeutic evidence base to agree a standard approach to intervention. Although we already have a range of potentially effective treatments, further clinical trials are required to optimise therapeutic intervention.

Published
2021
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25. Rheumatoid arthritis and idiopathic pulmonary fibrosis: a bidirectional Mendelian randomisation study

Author

Olivia C Leavy, Leticia Kawano-Dourado, Iain D Stewart, Jennifer K Quint, Joshua J Solomon, Raphael Borie, Bruno Crestani, Louise V Wain, R Gisli Jenkins, Philippe Dieudé, and Cosetta Minelli

Abstract

IntroductionA usual interstitial pneumonia (UIP) pattern of lung injury is a key feature of idiopathic pulmonary fibrosis (IPF) and is also observed in up to 40% of individuals with rheumatoid arthritis (RA) related Interstitial Lung Disease (RA-ILD). The RA-UIP phenotype could result from either a causal relationship of RA on UIP or vice versa, or from a simple co-occurrence of RA and IPF due to shared demographic, genetic or environmental risk factors.MethodsWe used two-sample bidirectional Mendelian Randomisation (MR) to investigate the causal effects of RA on UIP and of UIP on RA, using variants from genome-wide association studies of RA (separately for seropositive and seronegative RA) and of IPF as genetic instruments. We conducted inverse-variance-weighted fixed-effect MR as a primary analysis and undertook sensitivity analyses to assess potential violations of the key MR assumption of no (horizontal) pleiotropy.ResultsSeropositive RA showed a significant protective effect on IPF (Odds Ratio, OR = 0.93; 95% Confidence Interval, CI: 0.87-0.99; P=0.032), while the MR in the other direction showed a strongly significant causal effect of IPF on seropositive RA (OR = 1.06, 95% CI: 1.04-1.08, P=1.22×10−11).ConclusionOur findings support the hypothesis that RA-UIP may be due to a cause-effect relationship between IPF and RA, rather than due to a coincidental occurrence of IPF in patients with RA. The causal effect of IPF on seropositive RA suggests that patho-mechanisms involved in the development of UIP may promote RA and would suggest that screening for UIP in asymptomatic RA patients may be warranted and may influence therapy management of patients with RA-UIP.

Published
2022
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26. Rheumatological evaluation of patients with interstitial lung disease

Author

Bruno Crestani, Philippe Dieudé, Marie-Pierre Debray, Raphael Borie, Sébastien Ottaviani, and S. Khaleche

Subjects
Male, Pathology, medicine.medical_specialty, Immunology, MEDLINE, behavioral disciplines and activities, environment and public health, Text mining, Rheumatology, medicine, Humans, Immunology and Allergy, Connective Tissue Diseases, Lung, Aged, Aged, 80 and over, business.industry, fungi, Interstitial lung disease, General Medicine, Middle Aged, respiratory system, medicine.disease, Connective tissue disease, Respiratory Function Tests, respiratory tract diseases, Sjogren's Syndrome, Feature (computer vision), Female, CTD, Lung Diseases, Interstitial, business
Abstract

Objective: Interstitial lung disease (ILD) is a common feature of connective tissue disease (CTD). The diagnosis of CTD-ILD can be challenging and is important for therapeutic decisions. In this st...

Published
2021
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28. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography in polymyalgia rheumatica: an observational study

Author

Charlotte, Casadepax-Soulet, Khadija, Benali, Bruno, Crestani, Eve, Piekarski, Besma, Mahida, Esther, Ebstein, Pierre-Antoine, Juge, Marine, Forien, Philippe, Dieudé, and Sébastien, Ottaviani

Subjects
Rheumatology, Immunology, Immunology and Allergy
Abstract

Polymyalgia rheumatica (PMR) is an inflammatory disease with a diagnosis that is sometimes difficult to establish. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) might be helpful. We analysed the usefulness of 18F-FDG PET/CT for the diagnosis of PMR.This was an observational retrospective study of individuals with PMR who underwent 18F-FDG PET/CT and a control group. We assessed clinical and 18F-FDG PET/CT characteristics. Sixteen sites were studied. The number of sites with significant FDG uptake, the mean maximum standardised uptake value (SUVmax) and the highest SUVmax value were assessed for each patient.Data for 123 patients with PMR (37 with corticosteroids [CSTs] use) were analysed; 85 had new-onset PMR. As compared with the 75 controls, patients with new-onset PMR had higher mean ± SD number of sites with significant FDG uptake (11.3 ± 3.3 vs. 0.9 ± 1.1, p0.001) and higher SUVmax scores (p0.001). A cut-off of 5 hypermetabolic sites provided sensitivity of 96.5% and specificity 100%. For the total SUVmax score, a cut-off of 3 had the best sensitivity (92.6%) and specificity (86.1%). As compared with PMR patients using CSTs, those who were CST-naive had significantly higher CRP level (p0.001), number of sites with significant FDG uptake (p0.001) and SUVmax scores (p0.01). In contrast, large-vessel vasculitis was more frequent in patients receiving CSTs than CST-naive patients (27% vs. 8%, p0.01).The number of hypermetabolic sites or SUVmax quantification might be useful for PMR diagnosis, and CSTs might affect the results of 18F-FDG PET/CT.

Published
2022
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29. Current favourable 10-year outcome of patients with early rheumatoid arthritis: data from the ESPOIR cohort

Author

Maxime Dougados, Jean-Pierre Daurès, Alain Saraux, Philippe Dieudé, Philippe Goupille, Nathalie Rincheval, René-Marc Flipo, Bernard Combe, Alain Cantagrel, Thierry Schaeverbeke, Patrick Boumier, Olivier Vittecoq, Jean Sibilia, Bruno Fautrel, Francis Berenbaum, and Xavier Mariette

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, Population, Comorbidity, Outcome (game theory), Arthritis, Rheumatoid, Rheumatology, Internal medicine, Intensive care, medicine, Humans, Pharmacology (medical), education, education.field_of_study, business.industry, Remission Induction, Early rheumatoid arthritis, Middle Aged, medicine.disease, Antirheumatic Agents, Rheumatoid arthritis, Cohort, Female, France, business, Early arthritis, Follow-Up Studies
Abstract

Objective To report the 10-year outcome of an inception cohort of patients with early rheumatoid arthritis (RA), the ESPOIR cohort, and predictors of outcome. Methods From 2003 to 2005, 813 patients were included if they had early arthritis ( Results In total, 521 (64.1%) RA patients were followed up for 10 years; 35 (4.3%) died, which appears to be similar to the French general population. Overall, 480 (92.1%) patients received a DMARD; 174 (33.4%) received at least one biologic DMARD, 13.6% within 2 years. At year 10, 273 (52.4%) patients were in DAS28 remission, 40.1% in sustained remission, 14.1% in drug-free remission, 39.7% in CDAI remission. Half of the patients achieved a health assessment questionnaire-disability index (HAQ-DI) < 0.5. SF-36 physical component and pain were well controlled. Structural progression was weak, with a mean change from baseline in modified Sharp score of 11.0 (17.9). Only 34 (6.5%) patients required major joint surgery. A substantial number of patients showed new comorbidities over 10 years. Positivity for anti-citrullinated peptides antibodies (ACPA) was confirmed as a robust predictor of long-term outcome. Conclusions We report a very mild 10-year outcome of a large cohort of patients with early RA diagnosed in the early 2000s, which was much better than results for a previous cohort of patients who were recruited in 1993. This current favourable outcome may be related to more intensive care for real-life patients.

Published
2021
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30. MRI Features Associated With the Detection of Microbial Pathogens by CT-Guided Biopsy in Septic Spondylodiscitis

Author

Géraldine Bart, Christophe Rioux, Pascal Richette, Hervé Jacquier, Véronique Joly, Emilie Chotard, Elisabeth Palazzo, Yazdan Yazdanpanah, Benoit Le Goff, Marine Forien, Sébastien Ottaviani, Philippe Dieudé, Julia Goossens, and Germain Jelin

Subjects
Adult, Image-Guided Biopsy, Male, Spondylodiscitis, medicine.medical_specialty, Discitis, Rheumatology, Interquartile range, Edema, Biopsy, medicine, Humans, Intervertebral Disc, Abscess, Aged, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Intervertebral disc, Middle Aged, medicine.disease, Magnetic Resonance Imaging, medicine.anatomical_structure, Granuloma, Radiology, medicine.symptom, Tomography, X-Ray Computed, business
Abstract

OBJECTIVE The aim of this study was to assess the magnetic resonance imaging (MRI) features associated with microbial pathogen detection by computed tomography (CT)-guided biopsy in patients with suspected septic spondylodiscitis. METHODS For the last 10-year period, we analyzed the medical records of patients who underwent MRI and CT-guided biopsy for suspected septic spondylodiscitis. Clinical characteristics were recorded. The following MRI features were assessed: edema or contrast enhancement of the intervertebral disc, adjacent vertebrae, epidural and paravertebral space, presence of abscess, and paravertebral edema size. A positive biopsy was defined by pathogen identification on bacterial analysis or the presence of granuloma on histology. Predictors of a positive biopsy were assessed with a logistic regression model. RESULTS We analyzed data for 61 patients (34 [56%] male; mean age, 59.9 ± 18.0 years); for 35 patients (57%), CT-guided biopsy was positive for a pathogen. The 4 MRI findings significantly associated with a positive biopsy were epiduritis, greater than 50% vertebral endplate edema, loss of intradiscal cleft, and abscess. The size of paravertebral edema was greater with a positive than negative biopsy (median, 15.9 [interquartile range, 11.3-21.3] vs 7.3 [4.6-12.9] mm; p = 0.004). On multivariable analysis, epiduritis was the only independent predictor of a positive biopsy (adjusted odds ratio, 7.4 [95% confidence interval, 1.7-31.4]; p = 0.006). CONCLUSIONS Epiduritis and the size of paravertebral edema on MRI are associated with detection of a microbial pathogen in suspected septic spondylodiscitis. For patients without these MRI signs, the need for further investigations such as enriched or prolonged cultures, a second CT-guided biopsy, or even surgical biopsy need to be discussed.

Published
2020
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31. 18F-FDG PET/CT in bone sarcoidosis: an observational study

Author

Raphael Borie, Eve Piekarski, Sébastien Ottaviani, Khadija Benali, Marine Forien, Philippe Dieudé, Elisabeth Palazzo, Lucie Demaria, Bruno Crestani, and Julia Goossens

Subjects
030203 arthritis & rheumatology, medicine.medical_specialty, Axial skeleton, medicine.diagnostic_test, Sternum, business.industry, Retrospective cohort study, General Medicine, medicine.disease, Rheumatology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Internal medicine, Biopsy, medicine, Humerus, 030212 general & internal medicine, Radiology, Sarcoidosis, business, Pelvis
Abstract

Bone sarcoidosis is usually rare. Imaging procedures such as fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) can reveal bone sarcoidosis with better sensitivity than conventional radiography. We aimed to describe bone sarcoidosis involvement detected with 18F-FDG PET/CT. This was an observational retrospective study of individuals with pulmonary sarcoidosis who underwent 18F-FDG PET/CT. According to the ATS/ERS/WASOG criteria, sarcoidosis was diagnosed by the presence of clinical and/or imaging features of sarcoidosis and evidence of non-caseating epithelioid granulomas on a biopsy. We assessed clinical and 18F-FDG PET/CT characteristics. Data for 85 patients with sarcoidosis (56.5% female, median age 47 [range 21–80] years) were analyzed. The median follow-up was 4 years. Among 56 patients, sarcoidosis occurred in more than three organs. According to ATS/ERS/WASOG criteria, bone sarcoidosis was diagnosed in 12 (14%) patients. The spine was the most commonly affected location (92%, n = 11), followed by the pelvis (67%, n = 8), sternum (33%, n = 4), humerus (25%, n = 3), and fingers (17%, n = 2). Only peripheral adenopathy was associated with bone sarcoidosis (p = 0.04). Seven patients had a 18F-FDG PET/CT follow-up, all showing a decrease of bone lesions. Bone sarcoidosis occurred in 14% of patients with sarcoidosis, affecting multiple bones and mostly the axial skeleton. 18F-FDG PET/CT seems a sensitive tool for diagnosis and follow-up of bone sarcoidosis.

Published
2020
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33. Pilot experience of multidisciplinary team discussion dedicated to inherited pulmonary fibrosis

Author

Ralph Epaud, Serge Amselem, Philippe Bonniaud, Clairelyne Dupin, Aurélie Plessier, Annick Clement, Vincent Cottin, Flore Sicre de Fontbrune, Lidwine Wemeau-Stervinou, Vincent Bunel, Diane Bouvry, Marie Pierre Debray, Caroline Kannengiesser, Aurélie Cazes, Bruno Crestani, Marie Legendre, Raphael Borie, Ibrahima Ba, Nadia Nathan, Philippe Dieudé, Elodie Lainey, Laurent Gouya, Pascale Fanen, Centre de Référence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Avicenne [AP-HP], Centre de Référence des Maladies Pulmonaires Rares [AP-HP Bobigny], Centre de référence national pour les maladies respiratoires rares de l’enfant RespiRare [CHU Trousseau], Service de Pneumologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Centre des maladies respiratoires rares Respirare [CHI Créteil], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), AP-HP Hôpital universitaire Robert-Debré [Paris], Hopital Saint-Louis [AP-HP] (AP-HP), Centre de compétences des maladies pulmonaires rares de l'adulte [CHU Lille] (CRMPR), Service de Pneumologie et Immuno-Allergologie [CHU LIlle], Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pole Cardio-vasculaire et pulmonaire [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie [Hôpital Louis Pradel – CHU Lyon] (Centre de Référence des Maladies Pulmonaires Rares), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-CHU Lyon, and Couvet, Sandrine

Subjects
Male, MESH: Familial, multidisciplinary discussion, Interstitial pulmonary fibrosis, Surfactant, TERT, Telomerase, Pulmonary Fibrosis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Organ transplantation, 0302 clinical medicine, Pulmonary fibrosis, Pharmacology (medical), 030212 general & internal medicine, Child, Genetics (clinical), medicine.diagnostic_test, Interstitial lung disease, General Medicine, Middle Aged, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], Child, Preschool, Female, Familial, Adult, medicine.medical_specialty, Adolescent, Genetic counseling, MEDLINE, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Multidisciplinary team, Surface-Active Agents, Young Adult, 03 medical and health sciences, medicine, Humans, Genetic Testing, Intensive care medicine, Aged, Genetic testing, business.industry, Research, lcsh:R, Infant, medicine.disease, Human genetics, 030228 respiratory system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, RNA, business
Abstract

Background Genetic testing is proposed for suspected cases of monogenic pulmonary fibrosis, but clinicians and patients need specific information and recommendation about the related diagnosis and management issues. Because multidisciplinary discussion (MDD) has been shown to improve accuracy of interstitial lung disease (ILD) diagnosis, we evaluated the feasibility of a genetic MDD (geneMDD) dedicated to the indication for and interpretation of genetic testing. The geneMDD group met monthly and included pediatric and adult lung specialists with ILD expertise, molecular and clinical geneticists, and one radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Results Since 2016, physicians from 34 different centers in 7 countries have participated in the geneMDD. The medical files of 95 patients (53 males) have been discussed. The median age of patients was 43 years [range 0–77], 10 were ≤ 15 years old, and 6 were deceased at the time of the discussion. Among 85 analyses available, the geneMDD considered the rare gene variants pathogenic for 61: 37 variants in telomere-related genes, 23 variants in surfactant-related genes and 1 variant in MARS. Genetic counseling was offered for relatives of these patients. The geneMDD therapeutic proposals were as follows: antifibrotic drugs (n = 25), steroids or immunomodulatory therapy (n = 18), organ transplantation (n = 21), watch and wait (n = 21), or best supportive care (n = 4). Conclusion Our experience shows that a dedicated geneMDD is feasible regardless of a patient’s age and provides a unique opportunity to adapt patient management and therapy in this very rare condition.

Published
2019
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34. Polymyalgia rheumatica following COVID-19 vaccination: A case-series of ten patients

Author

Sébastien Ottaviani, Pierre-Antoine Juge, Marine Forien, Esther Ebstein, Elisabeth Palazzo, and Philippe Dieudé

Subjects
musculoskeletal diseases, Original Paper, COVID-19 Vaccines, Rheumatology, Polymyalgia Rheumatica, SARS-CoV-2, ultrasound, Giant Cell Arteritis, Vaccination, COVID-19, Humans, infection
Abstract

Objectives Polymyalgia rheumatica (PMR) is the commonest inflammatory disorder of the elderly; an association with environmental triggers and a deregulated immune response have been described. The aim of this study was to investigate the association of environmental triggers before the onset of PMR. Material and methods The database of 58 consecutive PMR patients recruited from a single rheumatology secondary care setting was retrospectively analyzed to investigate the frequency of environmental triggers and correlations with clinical characteristics, ultrasound and laboratory data. Results Fifteen PMR patients (26%) described a connection with environmental agents: six PMR patients reported a vaccination, 4 reported a respiratory tract infection, 5 reported seasonal influenza before the onset of the disease. The model of multivariate linear regression which better predicted a shorter time to normalize inflammatory reactants (R2 = 27.46%, p = 0.0042) comprised the presence of an environmental trigger and a higher PCR. A linear regression analysis confirmed an inverse correlation between PCR at onset and time to normalize inflammatory reactant (r = –0.3031, p = 0.0208). A significant correlation was demonstrated between presence of environmental trigger and shorter time to normalize inflammation (r = –0.5215, p< 0.0001), and lesser frequency of gleno-humeral synovitis on US (r = –0.3774, p = 0.0038). Conclusions Our work describes a correlation between environmental triggers in PMR and higher CRP at diagnosis, faster response to therapy, and milder shoulder synovitis. We may suppose that these patients belong to a more specific subtype of PMR, in whom external stimuli, such as vaccination or infection, may lead to a deregulated response within the context of an impaired senescent immuno-endocrine system.

Published
2021

35. Interstitial lung diseases associated with mutations of poly(A)-specific ribonuclease: A multicentre retrospective study

Author

Quentin, Philippot, Caroline, Kannengiesser, Marie Pierre, Debray, Clément, Gauvain, Ibrahima, Ba, Margherita, Vieri, Anne, Gondouin, Jean-Marc, Naccache, Martine, Reynaud-Gaubert, Yurdagul, Uzunhan, Benjamin, Bondue, Dominique, Israël-Biet, Philippe, Dieudé, Cécile, Fourrage, Elodie, Lainey, Effrosyne, Manali, Spyros, Papiris, Lidwine, Wemeau, Sandrine, Hirschi, Hervé, Mal, Hilario, Nunes, Frédéric, Schlemmer, Elodie, Blanchard, Fabian, Beier, Vincent, Cottin, Bruno, Crestani, and Raphaël, Borie

Subjects
Pulmonary and Respiratory Medicine, Exoribonucleases, Mutation, Humans, Lung Diseases, Interstitial, Idiopathic Pulmonary Fibrosis, Retrospective Studies
Abstract

Poly(A)-specific ribonuclease (PARN) mutations have been associated with familial pulmonary fibrosis. This study aims to describe the phenotype of patients with interstitial lung disease (ILD) and heterozygous PARN mutations.We performed a retrospective, observational, non-interventional study of patients with an ILD diagnosis and a pathogenic heterozygous PARN mutation followed up in a centre of the OrphaLung network.We included 31 patients (29 from 16 kindreds and two sporadic patients). The median age at ILD diagnosis was 59 years (range 54 to 63). In total, 23 (74%) patients had a smoking history and/or fibrogenic exposure. The pulmonary phenotypes were heterogenous, but the most frequent diagnosis was idiopathic pulmonary fibrosis (n = 12, 39%). Haematological abnormalities were identified in three patients and liver disease in two. In total, 21 patients received a specific treatment for ILD: steroids (n = 13), antifibrotic agents (n = 11), immunosuppressants (n = 5) and N-acetyl cysteine (n = 2). The median forced vital capacity decline for the whole sample was 256 ml/year (range -363 to -148). After a median follow-up of 32 months (range 18 to 66), 10 patients had died and six had undergone lung transplantation. The median transplantation-free survival was 54 months (95% CI 29 to ∞). Extra-pulmonary features were less frequent with PARN mutation than telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) mutation.IPF is common among individuals with PARN mutation, but other ILD subtypes may be observed.

Published
2021

37. Lack of association between the TNFAIP3 rs2230926 variant and rheumatoid arthritis-associated lymphoma

Author

Joanna Kedra, Raphaele Seror, Philippe Dieudé, Arnaud Constantin, Eric Toussirot, Elias Kfoury, Charles Masson, Divi Cornec, Jean-Jacques Dubost, Laurent Marguerie, Sebastien Ottaviani, Franck Grados, Rakiba Belkhir, Olivier Fain, Bruno Fautrel, Peggy Philippe, Muriel Piperno, Bernard Combe, Olivier Lambotte, Christophe Richez, Jérémie Sellam, Thomas Sené, Guillaume Denis, Thierry Lequerre, Thierry Lazure, Xavier Mariette, and Gaetane Nocturne

Subjects
Arthritis, Rheumatoid, Lymphoma, Rheumatology, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Tumor Necrosis Factor alpha-Induced Protein 3
Published
2022
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38. Use of

Author

Marie, Pean de Ponfilly-Sotier, Florent L, Besson, Léa, Gomez, Sébastien, Ottaviani, Philippe, Dieudé, Stephane, Pavy, Xavier, Mariette, Raphaele, Seror, and Gaetane, Nocturne

Subjects
Fluorodeoxyglucose F18, Polymyalgia Rheumatica, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Giant Cell Arteritis, Spondylarthritis, Humans, Radiopharmaceuticals, Aged
Abstract

To evaluate the relevance ofIn 2 rheumatology departments, we identified PMR and atypical SpA patients who underwentBetween September 2012 and August 2018, we enrolled 35 PMR and 27 SpA patients (median [interquartile range] age 71 years [63.5-74.5] and 54 years [41.5-63], P0.001).

Published
2021

39. Practical Management of patients on anti-IL6R therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author

Jacques Morel, Anne Tournadre, Jérémie Sellam, Yoram Bouhnik, Divi Cornec, Valérie Devauchelle-Pensec, Philippe Dieudé, Philippe Goupille, Nicolas Kluger, Estibaliz Lazaro, Benoit Le Goff, Victor de Lédinghen, Thierry Lequerré, Gaëtane Nocturne, Raphaèle Seror, Marie-Elise Truchetet, Frank Verhoeven, Thao Pham, and Christophe Richez

Subjects
Arthritis, Rheumatoid, Inflammation, Rheumatology, Antirheumatic Agents, Humans
Published
2021

40. Secukinumab and ustekinumab treatment in psoriatic arthritis: results of a direct comparison

Author

Chi Duc Nguyen, Nicolas Cohen, Bruno Fautrel, Jean-Hugues Salmon, Elisabeth Gervais, Guy Baudens, Céline Labadie, Eric Houvenagel, Maeva Kyheng, Pascal Richette, Isabelle Chary-Valckenaere, X. Deprez, Thao Pham, Pascal Claudepierre, Benoît Flachaire, René-Marc Flipo, Corinne Miceli-Richard, Philippe Dieudé, Peggy Philippe, Christophe Richez, Laurent Marguerie, Damien Loeuille, Pierre Lafforgue, Jérémie Sellam, N. Segaud, Jean-Guillaume Letarouilly, Florence Tubach, Marie-Hélène Guyot, Université de Lille, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Aix Marseille Université (AMU), Université de Bordeaux (UB), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Sorbonne Université (SU), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Université de Reims Champagne-Ardenne (URCA), Université Paris Cité (UPCité), Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and pithioux, martine

Subjects
Male, medicine.medical_specialty, real-world, Subgroup analysis, Kaplan-Meier Estimate, Antibodies, Monoclonal, Humanized, ustekinumab, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Rheumatology, Internal medicine, Ustekinumab, Outcome Assessment, Health Care, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Adverse effect, Propensity Score, Aged, Retrospective Studies, 030203 arthritis & rheumatology, psoriatic arthritis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, secukinumab, Hazard ratio, Arthritis, Psoriatic, persistence, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Middle Aged, medicine.disease, 3. Good health, Discontinuation, Methotrexate, Withholding Treatment, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Secukinumab, Female, Dermatologic Agents, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Cohort study, medicine.drug, Follow-Up Studies
Abstract

Objectives To evaluate the characteristics of patients (pts) with PsA treated by ustekinumab (UST) or secukinumab (SEK) and to compare real-world persistence of UST and SEK in PsA. Methods In this retrospective, national, multicentre cohort study, pts with PsA (CASPAR criteria or diagnosis confirmed by the rheumatologist) initiating UST or SEK with a follow-up ≥6 months were included from January 2011 to April 2019. The persistence between SEK and UST was assessed after considering the potential confounding factors by using pre-specified propensity-score methods. Causes of discontinuation and tolerance were also collected. Results A total of 406 pts were included: 245 with UST and 161 with SEK. The persistence rate was lower in the UST group compared with the SEK group [median persistence 9.4 vs 14.7 months; 26.4% vs 38.0% at 2 years; weighted hazard ratio (HR) = 1.42; 95% CI: 1.07, 1.92; P =0.015]. In subgroup analysis, the persistence rate of SEK associated with MTX was significantly higher than that of UST associated with MTX: HR = 2.20; 95% CI: 1.30, 3.51; P =0.001, in contrast to SEK vs UST monotherapy: HR = 1.06; 95% CI: 0.74, 1.53; P =0.75. Discontinuation due to inefficacy was reported in 91.7% (SEK) and 82.4% (UST) of pts. Discontinuation due to an adverse event was reported in 12.2% (SEK) and 7.7% (UST) of pts. Conclusion In this first study comparing UST and SEK, the persistence of SEK was higher than that of UST in PsA. In subgroup analysis, this difference was only found in association with MTX.

Published
2021
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41. Efficacité et sécurité de l’anakinra dans la goutte associée à une insuffisance rénale chronique de stade 4 ou 5 ou à une transplantation rénale : étude rétrospective multicentrique

Author

Nicolas Rosine, P.A. Juge, Marine Forien, Marie-Elise Truchetet, Thierry Schaeverbeke, Thomas Bardin, Hang-Korng Ea, Pascal Richette, Frédéric Lioté, Bernard Bannwarth, Christophe Richez, Clotilde Loustau, Sébastien Ottaviani, Philippe Dieudé, Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université Paris Diderot - Paris 7 (UPD7), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier

Subjects
[SDV] Life Sciences [q-bio], 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract

Resume Objectifs Les inhibiteurs de l’interleukine (IL)-1β, efficaces dans les crises de goutte, sont recommandes en cas de contre-indications a la prise en charge standard, notamment insuffisance renale chronique (IRC) de stade 4 ou 5. Or, il existe peu de donnees disponibles sur l’efficacite et la securite de ces agents dans cette population de patients. Nous avons souhaite explorer l’efficacite et la securite de l’anakinra utilise pour traiter les crises de goutte chez des patients presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale. Methodes Cette etude retrospective menee dans trois centres universitaires a inclus des patients consecutifs presentant une IRC de stade 4 ou 5 ou ayant subi une transplantation renale qui prenaient de l’anakinra en traitement d’une arthrite goutteuse aigue et avaient effectue au moins une visite de suivi. L’efficacite, la survenue d’infections et les variations de la fonction renale ont ete consignees. Resultats Sur les 31 patients inclus (24 hommes, âge moyen 72 ± 11 ans), 25 n’avaient pas subi de transplantation et presentaient une IRC de stade 4 ou 5 (estimation du debit de filtration glomerulaire moyen [eDFG] selon la formule MDRD 22,7 ± 6,5 mL/min/1,73 m2) et 6 avaient subi une transplantation renale (eDFG moyen 41,5 ± 22,8 mL/min/1,73 m2). La duree mediane de la goutte etait de 3,5 ans et le taux moyen d’uricemie de 8,7 mg/dL. Vingt-et-un patients (68 %) presentaient des tophi et 21, une arthropathie goutteuse. L’anakinra a ete efficace chez tous les patients (EVA final 10 et CRP finale 10 mg/L). Dix patients (32 %) etaient dependants de l’anakinra (c.-a-d. qu’un traitement prolonge d’anakinra etait necessaire). Une infection grave a ete enregistree chez une seule patiente, trois mois apres l’instauration de l’anakinra. Aucune variation significative de la fonction renale n’a ete observee. Conclusion L’anakinra peut constituer une option therapeutique sure chez les patients goutteux presentant une IRC a un stade avance. Des etudes comparatives randomisees supplementaires sont necessaires pour confirmer nos resultats.

Published
2019
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42. Bowel-associated dermatosis arthritis syndrome: A case report with first positron emission tomography analysis

Author

Sébastien Ottaviani, Elisabeth Palazzo, Germain Jelin, Philippe Dieudé, Marine Forien, Nolan Hassold, Lydia Deschamps, and Vincent Descamp

Subjects
medicine.medical_specialty, positron emission tomography, medicine.diagnostic_test, Bowel-associated dermatosis–arthritis syndrome, business.industry, Obesity Surgery, Context (language use), Case Report, Dermatology, bacterial overgrowth, Bacterial overgrowth, medicine.disease, bowel-associated dermatosis-arthritis syndrome, digestive system diseases, PET, positron emission tomography, PET - Positron emission tomography, Positron emission tomography, BADAS, bowel-associated dermatosis-arthritis syndrome, medicine, Rare syndrome, In patient, Radiology, arthralgia, business, skin eruption
Abstract

Bowel-associated dermatosis-arthritis syndrome (BADAS) is a rare syndrome that was described for the first time in 19711 in patients who received bypass obesity surgery,2 taking the name of bowel bypass syndrome. Similar cases were reported with patients who had inflammatory bowel disease3 leading to the name of BADAS. It causes both arthralgia and skin eruptions, which, in context of bowel disease, has to put us in mind of the possibility of the diagnosis. Here we report a case of a positron emission tomography (PET) scanner description.

Published
2019

44. Effectiveness and safety of anakinra in gout patients with stage 4–5 chronic kidney disease or kidney transplantation: A multicentre, retrospective study

Author

Bernard Bannwarth, Frédéric Lioté, Marie-Elise Truchetet, Marine Forien, Christophe Richez, Nicolas Rosine, Sébastien Ottaviani, Philippe Dieudé, P.A. Juge, Thierry Schaeverbeke, Hang-Korng Ea, Thomas Bardin, Pascal Richette, and Clotilde Loustau

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, Gout, Population, Renal function, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Kidney transplantation, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Anakinra, education.field_of_study, business.industry, Retrospective cohort study, Middle Aged, medicine.disease, Kidney Transplantation, Transplantation, Interleukin 1 Receptor Antagonist Protein, Treatment Outcome, Antirheumatic Agents, Female, business, Follow-Up Studies, Glomerular Filtration Rate, medicine.drug, Kidney disease
Abstract

Objectives Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4–5 chronic kidney disease (CKD) patients. However, efficacy and safety data regarding these agents are lacking in this population. We aimed to investigate the efficacy and safety of anakinra for the treatment of gout flares in patients with stage 4–5 CKD or renal transplantation. Methods This retrospective study encompassing 3 academic centres included consecutive patients with stage 4–5 CKD or kidney transplantation who received anakinra for the treatment of acute gouty arthritis and completed at least one follow-up visit. Efficacy, occurrence of infection, and renal function variations were recorded. Results Of the 31 included patients (24 men, mean age 72 ± 11 years), 25 were non-transplant subjects with stage 4–5 CKD (mean estimated glomerular filtration rate, MDRD formula (eGFR) 22.7 ± 6.5 mL/min/1.73 m 2 ), and six had undergone kidney transplantation (mean eGFR 41.5 ± 22.8 mL/min/1.73 m 2 ). Median gout duration was 3.5 years, and the mean serum urate (SUA) level was 8.7 mg/dL. Twenty-one (68%) patients had tophi, and 21 had gout arthropathy. Anakinra was efficacious in all patients (final VAS 10 and CRP level 10 mg/L). Ten patients (32%) were anakinra dependent (i.e., required prolonged treatment with anakinra). A serious infection was recorded in only one patient, occurring 3 months after starting anakinra. No significant variation in renal function was observed. Conclusion Anakinra may be a safe therapeutic option for gout patients with advanced CKD. Further randomized controlled studies are required to confirm our results.

Published
2018
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45. PRACTICAL MANAGEMENT of patients on anti-TNF therapy: Practical guidelines drawn up by the Club Rhumatismes et Inflammation (CRI)

Author

Marie-Elise Truchetet, Anne Tournadre, Estibaliz Lazaro, Jacques Morel, Raphaèle Seror, Philippe Dieudé, Denis Jullien, Thao Pham, Philippe Goupille, Thierry Lequerré, Valérie Devauchelle-Pensec, Jérémie Sellam, Gaetane Nocturne, Yoram Bouhnik, Victor de Lédinghen, Divi Cornec, Christophe Richez, Nicolas Kluger, Benoit Le Goff, Frank Verhoeven, Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Rhumatologie [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Rhumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Gastroentérologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), GH Bichat - Service de Rhumatologie, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Service de Dermatologie [Hôpital Bichat – Claude-Bernard - APHP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Médecine Interne [CHU de Bordeaux], CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU de Bordeaux], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Unité d'Hépatologie et transplantation hépatique, Hôpital Haut-Lévêque, CHU Bordeaux, Pessac, France, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Service de Rhumatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Service de Rhumatologie, Hôpital Sainte-Marguerite, Aix Marseille

Subjects
030203 arthritis & rheumatology, Inflammation, medicine.medical_specialty, business.industry, MEDLINE, 3. Good health, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Antirheumatic Agents, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Humans, Tumor Necrosis Factor Inhibitors, 030212 general & internal medicine, Club, Intensive care medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021
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46. Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry

Author

Maria Margarida Cunha, Gabriela Schmajuk, Rebecca Hasseli, Namrata Singh, Tiffany Y.T. Hsu, Milena A. Gianfrancesco, Anja Strangfeld, Ranjeny Thomas, Naomi J Patel, Thierry Thomas, Philippe Dieudé, Kimme L. Hyrich, Emily Sirotich, Laura Trupin, Liselotte Tidblad, Jinoos Yazdany, René Marc Flipo, Licia Maria Henrique da Mota, Andrea M Seet, Samar Al Emadi, Carolina A. Isnardi, Saskia Lawson-Tovey, Alí Duarte-García, Hendrik Schulze-Koops, Manuel F. Ugarte-Gil, Vanessa L. Kronzer, Philip Robinson, Lindsay Jacobsohn, Elsa F Mateus, Pedro Machado, Ana Paula Monteiro Gomides, Jean W. Liew, Guillermo A. Berbotto, Miguel Bernardes, Patricia P. Katz, Martin Schäfer, Guillermo J. Pons-Estel, Ulf Müller-Ladner, Jeffrey A. Sparks, Elena Nikiphorou, Christof Specker, Paul Sufka, Zara Izadi, Loreto Carmona, Stephanie Rush, Sandra Lúcia Euzébio Ribeiro, Maria O Valenzuela-Almada, Kristin M. D’Silva, Emily L Gilbert, Raphaèle Seror, Laure Gossec, Beth I Wallace, Viviane Angelina de Souza, Akpabio Akpabio, Jérôme Avouac, Leanna Wise, Wendy Costello, Zachary S. Wallace, Suleman Bhana, Jonathan S. Hausmann, Lianne Kearsley-Fleet, Bernd Raffeiner, Carlo Alberto Scirè, Rebecca Grainger, Sparks, J, Wallace, Z, Seet, A, Gianfrancesco, M, Izadi, Z, Hyrich, K, Strangfeld, A, Gossec, L, Carmona, L, Mateus, E, Lawson-Tovey, S, Trupin, L, Rush, S, Katz, P, Schmajuk, G, Jacobsohn, L, Wise, L, Gilbert, E, Duarte-Garcia, A, Valenzuela-Almada, M, Pons-Estel, G, Isnardi, C, Berbotto, G, Hsu, T, D'Silva, K, Patel, N, Kearsley-Fleet, L, Schafer, M, Ribeiro, S, Al Emadi, S, Tidblad, L, Scire, C, Raffeiner, B, Thomas, T, Flipo, R, Avouac, J, Seror, R, Bernardes, M, Cunha, M, Hasseli, R, Schulze-Koops, H, Muller-Ladner, U, Specker, C, De Souza, V, Da Mota, L, Gomides, A, Dieude, P, Nikiphorou, E, Kronzer, V, Singh, N, Ugarte-Gil, M, Wallace, B, Akpabio, A, Thomas, R, Bhana, S, Costello, W, Grainger, R, Hausmann, J, Liew, J, Sirotich, E, Sufka, P, Robinson, P, Machado, P, and Yazdany, J

Subjects
Male, medicine.medical_specialty, abatacept, Coronavirus disease 2019 (COVID-19), Immunology, tumour necrosis factor inhibitors, tumour necrosis factor inhibitor, Antirheumatic Agents/therapeutic use, Rheumatoid Arthritis, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, rituximab, Rheumatology, Arthritis, Rheumatoid/complications, Internal medicine, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Registries, Interleukin 6, Aged, 030203 arthritis & rheumatology, biology, business.industry, SARS-CoV-2, Abatacept, Confounding, COVID-19, rheumatoid arthriti, Middle Aged, medicine.disease, Drug class, Rheumatoid arthritis, Antirheumatic Agents, COVID-19/complications, biology.protein, Rituximab, Female, business, medicine.drug
Abstract

ObjectiveTo investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA).MethodsWe analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders.ResultsOf 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity.ConclusionsPeople with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Published
2021
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47. MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and progression

Author

David A. Schwartz, Joanne J. van der Vis, Bruno Crestani, Marie-Christophe Boissier, Jan C. Grutters, Athina Trachalaki, Raphaël Porcher, Pierre-Antoine Juge, Thierry Schaeverbeke, Spyros Papiris, Nathalie Saidenberg-Kermanac’h, Catherine Boileau, Christophe Richez, Raphael Borie, Jorge Rojas-Serrano, Yurdagul Uzunhan, Theofanis Karageorgas, Montserrat I González-Pérez, Caroline Kannengiesser, Philippe Dieudé, Anna Jamnitski, Tracy J. Doyle, Leticia Kawano-Dourado, René-Marc Flipo, Dimitrios T. Boumpas, Enrique Ambrocio-Ortiz, Dominique Valeyre, Ramcés Falfán-Valencia, Ivette Buendía-Roldán, Joyce S. Lee, Joshua J. Solomon, Coline H.M. van Moorsel, Marie-Pierre Debray, Romain Garofoli, Paul J. Wolters, Lidwine Wemeau-Stervinou, Fabienne Louis-Sydney, Mayra Mejía, Katarina M. Antoniou, Effrosyni D. Manali, Prodromos Sidiropoulos, and Hilario Nunes

Subjects
Lung Diseases, Vital capacity, medicine.medical_specialty, Clinical Sciences, Rheumatoid Arthritis, Gastroenterology, Interstitial Lung Disease, MUC5B, Autoimmune Disease, Pulmonary function testing, Promoter Regions, Arthritis, Rheumatoid, Idiopathic pulmonary fibrosis, Rare Diseases, Rheumatology, Genetic, Interquartile range, Clinical Research, Internal medicine, Rheumatoid, medicine, Genetics, Humans, Risk factor, Promoter Regions, Genetic, Lung, Aged, Proportional hazards model, business.industry, Mortality rate, Arthritis, Inflammatory and immune system, Interstitial lung disease, respiratory system, medicine.disease, Mucin-5B, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Arthritis & Rheumatology, Anesthesiology and Pain Medicine, Respiratory, Public Health and Health Services, Female, business, Interstitial, Lung Diseases, Interstitial
Abstract

Background The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD. Methods Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline. Results Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern. Conclusion In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.

Published
2021

48. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author

Mathieu Vautier, Florence Tubach, Marion Licois, Estelle Henry, Marie-Alexandra Alyanakian, Julien Poissy, Solaya Chalal, Anne Gysembergh-Houal, Stéphanie Alary, Sophie Diemunsch, Jonathan London, Camille Petit-Hoang, Ruben Benainous, Catherine Metzger, Olivier Benveniste, Hala Semri, Charléne Jouve, Robin Dhote, johann Cailhol, Elise Morawiec, Kristina Beziriganyan, Mathieu Oberlin, Paul Legendre, Hélène François, Claire Davoine, F Louni, Myriam Virlouvet, Stéphane Renaud, Christiane Verny, Bertrand Guidet, Bob Heger, Lara Zafrani, Pierre-Louis Tharaux, Mandy Nizard, Adrien Contejean, Segolene Toquet, Ulrich Clarac, Sylviane Ravato, Gaëtan Deslée, Frédéric De Blay, Christian Richard, Raphaël Porcher, Malikhone Chansombat, Marie Lachatre, Ines Ben-Mabrouk, Matthieu Uzzan, Lauren Demerville, Amélie Servettaz, Annabelle Pourbaix, Philippe Manivet, Fanny Charbonnier, Pierre-Grégoire Guinot, Alexandre Demoule, Nicolas Champtiaux, Nicolas Belaube, Jean-Pierre Riveline, Kamil Chitour, Joseph Emmerich, Arthur Neuschwander, Mickael Henriques, Anne Hutt, Arthur Pavot, Anne Rachline, Elena Fois, Audrey Phibel, Xavier Monnet, Jean-Charles Duclos-Vallée, Félix Ackermann, Maria Pereira, Anne Sophie Korganow, Elodie Drouet, Tabassome Simon, Morgane Faure, Anne Pattyn, Aida Zahrate-Ghoul, Karine Martin, Jean-Jacques Tudesq, Gladys Aratus, Kévin Cardet, Julien Pottecher, Eric Demonsant, Arsène Mekinian, Rémy Gauzit, Julie Smati, Robin Deleris, Jean-Simon Rech, Boris Bienvenu, Nicolas Lefebvre, Elodie Baudry, Nicolas Bonnet, Alexis Régent, François Weill, Lalia Djaghout, Anne Tréhan, Isabelle Lehir, Elena Kiouris, Sophie Renet, Yasmina Mekid, Vanessa Rathouin, David Montani, Annick Tibi, Anne Blanchard, Fanette Denies, Nathalie Menage, Guillaume Becker, Valérie Camara-Clayette, Loic Kassegne, Nathalie Chavarot, Aurélie Clan Hew Wai, Jeremy Arzoine, Louise Bondeelle, Mohamad Zaidan, S Lariven, Laurent Cylly, Edouard Flamarion, Chaouki Bouras, Florence Bellenfant, Melissa Clément, Lola-Jade Palmieri, Marie hélène Pari, Lionel Galicier, Valérie Dejean, Delphine Feyeux, Naima Sguiouar, Anne Bergeron, Laurence Annonay, Anouk Walter-Petrich, Camille Knosp, Laurence Drouard, Thiziri Sadaoui, Julie Delemazure, Antoine Parrot, Carole Burger, Laurence Berard, Nicolas Gambier, Eric Marquis, Isabelle Madeleine, Gwenaël Lorillon, Matthieu Resche-Rigon, Yves Hansmann, Claire Rouzaud, Hélène Gros, Sophie Caillat-Zucman, Bernard Cholley, Celine Wilpotte, Chistophe Willekens, Lydia Suarez, Syllia Belazouz, Valérie Pourchet-Martinez, Dhiaa Meriem Hai, Olivier Collange, Paul Jaubert, Marie-Thérèse Tremorin, Nathalie Marin, Diane Le Pluart, Madona Sakkal, Juliette Djadi-Prat, Alexandre Morel, Agathe Bounhiol, Xavier Jaïs, Nicolas Meyer, Vixra Keo, Michaël Darmont, Benedicte Giroux-Leprieur, Anatole Harrois, Anne Adda, Yaël Amara, Fanny Pommeret, Antony Canellas, Matheus Vieira, Clotilde Le Tiec Le Tiec, Corinne Pernot, Bernard Goichot, Céline Louapre, Roza Rahli, Anne Jacolot, Anne Daguenel-Nguyen, Marie Dubert, Anaïs Razurel, Aurelie Sautereau, Mitja Jevnikar, Pierre Faye, Jeanne CHAUFFiER, Mathieu Jozwiak, Laurent Savale, Florence Patin, Kahina Cheref, Mélanie Dehais, Paul Michel Mertes, Caroline Morbieu, Valérie Paquet, Dominique Roulot, Giovanna Melica, Pauline Jouany, Frédéric Schlemmer, Blandine Lehmann, Pascal Martel, Tomas Urbina, Yazdan Yazdanpanah, Veronique Joly, Damien Bergerot, Claire Courtin, Benjamin Fournier, Guillaume Grailles, Asmaa Mamoune, Caroline Gaudefroy, Charlotte Kaeuffer, Bruno Crestani, Thinhinane Bariz, C Rioux, Karine Celli Lebras, Sophie Granville, Marion Bouhris, Hugues Cordel, Jean-Marie Michot, Mohamed Belloul, Nadège Lemarié, Philippe Dieudé, Sylvie Le Gac, Matthieu Mahévas, Pascal Richette, Anaïs Codorniu, Camille Rolland-Debord, Edouard Lefèvre, Sophie-Rym Hamada, Tristan Martin, Vincent Castelain, Aude Rigolet, Valentin Greigert, Gaelle Leroux, Simon Valayer, Eliane Bertrand, Eric Vicaut, Stéphane Brin, Jacques-Eric Gottenberg, Olivier Clovet, Marc Bardou, Muriel Fartoukh, Valentina Isernia, Ada Clarke, Bao Phung, Grégoire Martin de Frémont, Jeanne Meunier, Gonçalo Boleto, David Lebeaux, Hassan Tarhini, Asmaa Mabrouki, Pascaline Choinier, Etienne Canouï, Eric D'Ortenzio, Constance Guillaud, Corine Nyanou, Alexandre Moores, Linda Gimeno, Victoire De Lastours, F-Xavier Lescure, Claire Montlahuc, Sophie Georgin-Lavialle, A Soria, Xavier Mariette, Sophie Ismael, Prissile Bakouboula, Olivier Lambotte, Jérémie Zerbit, Aude Jacob, Z Julia, Nathalie Dournon, Marthe Rigal, Mireille Adda, Nathan Ebstein, Frédéric Duée, Helene Chambrin-Lauvray, Ramdane Meftali, Hélène Lafoeste, Coralie Bloch Queyrat, Sabrina Brahmi, Catherine Le Bourlout, Nicolas Noel, Emmanuelle Guillot, Hakim Tayebi, Sandrine Briois, Anne-Lise Pouliquen, Lakhdar Mameri, Sophie-Caroline Sacleux, Nathalie Rozensztajn, Lelia Escaut, Clément Jourdaine, Cédric Pierron, Marc Garnier, Yves Cohen, Abdellatif Tazi, Maxence Decavele, Paul Henri Grisot, Patrice Cacoub, Laure Allanic, Amira Benattia, Martin Siguier, Luca Semerano, Jean-Sébastien Hulot, Jean-Jacques Mourad, Sara Sambin, Miguel Alejandro Vasquez-Ibarra, Nabil Raked, Christine Lemagner, Martin Dres, Clara Campos-Vega, Tali-Anne Szwebel, Benjamin Chaigne, Emmanuel Andrès, Gabriel Steg, Frédéric Blanc, Isabelle Peigney, Catherine Fauvaux, Côme Bureau, Samira Saleh-Mghir, Julie Jambon, Pierre Dupland, Anne Lise Jegu, Mamadou Salif Cisse, Damien Roux, Moez Jallouli, Philippe Blanche, Sébastien Cavelot, Sophie Ohlmann-Caillard, Louise-Laure Mariani, Adrien Michon, Alain Wynckel, Saskia Flamand, Safaa Nemlaghi, Benjamin G. Chousterman, Geoffroy Volle, Cécile Kedzia, Fanny Domont, Lee S. Nguyen, Férial Berbour, Pierre Diemunsch, Celine Dupré, Etienne Lengliné, Claire Tantet, Gaël Leprun, Sara Virolle, Perrine Guillaume-Jugnot, Soumeya Hammal, B. Duchemann, Mathilde Le Marchand, Vincent Poindron, Victor Lancon, Ruxandra Burlacu, Guillaume Lefèvre, Kamyl Baghli, Emilia Stan, Yann Nguyen, Olivier Sanchez, Olivier Sitbon, Loren Soyez-Herkert, Fanny Defrancq, Véronique Vigna, Aurélien Guffroy, Martine Meunier, Pierre Mora, Léa Resmini, Liem Binh Luong Nguyen, Jean-Luc Diehl, Johanna Oziel, Emmanuelle Bugnet, Lamiae Grimaldi, Olivia Daconceicao, Marie Matignon, Mourad Djadel, Yasmine Messaoudi, Hassan Joumaa, Isabelle Dusanter, Sarah Benghanem, Julien Mayaux, Marc Michel, Claire Pernin, Antoine Gros, Nassim Mahtal, Philippe Benoit, Cloé Comarmond, Laurence Lecomte, Patricia Senet, Sebastien Abad, Jérôme Pacanowski, Céline Leplay, Claire Aguilar, Cédric Sublon, Jesuthasan Denis, Régis Peffault de Latour, Gabrielle Archer, Alain Fourreau, Emmanuelle Blin, Lise Bernard, Alexandra Beurton, Alexandre Buffet, Pierre Le Guen, Clairelyne Dupin, Olivier Fain, A Gervais, Marc Humbert, Yves Allenbach, Alexandre Bourgoin, Agnes Maurer, Eric Noll, Virginie Elisee, Adrien Mirouse, Cecile Larcheveque, Carine Karachi, Samy Figueiredo, Hakim Meddah, Greggory Ducrocq, Jeanne Goupil de Bouille, Awa Ndiaye, Jessica Krause le Garrec, Maxime Dougados, Yasmina Ferfar, Damien Vimpere, Olivier Olivier, Annabelle Stoclin, Jean-Louis Teboul, Ridha Belilita, Serge Bureau, Naura Gamany, Emeline Colomba, Baptiste Duceau, Philippe Ravaud, Corinne Guerin, Florence Morin, Pélagie Thibaut, Younes Keroumi, Julie Chas, Elisabeth Coupez, Laetitia Languille, Mathias Cornic, Jean-Michel Molina, Caroline Pradon, Alison Klasen, Zakaria Ait Hamou, Armand Mekontso-Dessaps, Yurdagul Uzunhan, Samir Hamiria, Anne Godier, Elsa Feredj, Nessima Yelles, Jean-Benoit Arlet, Christine Broissand, Belkacem Asselate, Jaouad Benhida, Julien Le Marec, Nawal Derridj, Laurène Deconinck, A. Dossier, Eric Oksenhendler, Eva Chatron, Lucie Aunay, Candice Estellat, Julie Fillon, Marie Antignac, Jade Ghosn, Ilias Koumis, David Schmitz, Domitille Molinari, Soraya Fellahi, Bruno Mégarbane, Aline Frazier, Ramon Junquera, Vincent Provitolo, Marie Lecronier, Dimitri Fremont, Pierrick Le Borgne, Emmanuel Weiss, Faouzi Saliba, Stéphan Pavy, Geoffrey Rossi, Chloe McAvoy, Eric Mariotte, Dorothee Vallois, Sabrine Ouamri, Pierre Tissieres, Luc Mouthon, Blandine Denis, Celine Comparon, Emmanuelle Sacco, Frédéric Pène, Marjolaine Morgand, Vasco Honsel, Laure Choupeaux, Bruno Mourvillier, Ewa Kozaliewicz, Marie-Hélène Legros, Isabelle Debrix, Gabriel Nisand, Julien Chabert, Juliette Camuset, Stéphane Jauréguiberry, Lynda Chalal, Marine Livrozet, Lucie Biard, Elodie Perrodeau, Brigitte Sabatier, Raphael Borie, Rosa Da Silva, Nathalie Costedoat-Chalumeau, Emmanuel Chatelus, Jean-Christophe Corvol, Nathalie De Castro, David Boutboul, Benjamin Planquette, Anne Claire Desbois, François Danion, Brigitte Ranque, Amélie Cransac, Marine Nadal, Coralie Gernez, Yacine Boudali, Claire Madelaine, Georgina Maalouf, Jonathan Marey, Sophie Bayer, Antoine Fayol, Souad Benarab, Luc Haudebourg, Sophie Bulifon, Claire Pacheco, Philippe Durand, Olivier Hermine, Fanny Alby-Laurent, Geoffroy Liégeon, Axelle Fuentes, Jean-Daniel Lelievre, Gilles Garcia, Céline Verstuyft Verstuyft, Marie-Aude Penet, Constance Delaugerre, Nicolas Carlier, Aurélie Durel Maurisse, Gilles Pialoux, Zeina Louis, Marion Parisey, Pascal Lim, Gaelle Clavere, Martin De Sarcus, Marie Vayssettes, Thomas Papo, Adrien Joseph, Hilario Nunes, Hanane Fodil, Solen Kernéis, Antoine Bachelard, Jacques Duranteau, Karine Lacombe, Olivia Lenoir, Mathilde Vallet, Isabelle Brindele, Robin Charreteur, Elie Azoulay, Dorothée Chopin, Aïcha Bah, Moustafa Benafla, Marie Gilbert, Matthieu Lemoine, Abolfazl Mohebbi, Mathilde Noaillon, Amina Kebir, Virginie Zarrouk, Cécile Yelnik, Benjamin Terrier, Solène Fabre, Paul Crespin, Sarah Dalibey, Thierno Dieye, Renaud Felten, Oriane Puéchal, Pernelle Vauboin, Caroline Hauw-Berlemont, Gabriel Baron, Paul Vermes, Yvon Ruch, Dominique Dautel, Tassadit Hadjam, Anne-Marie Roques, Jean-Philippe Bastard, Younes El Amine, Damien Sène, Alaki Thiemele, Catherine Boussard, Vincent Fallet, Timothee Bironne, Damien Vanhoye, Guillaume Geri, Amine Ghembaza, Bertrand Dunogue, Nadia Anguel, Laure Berton, Caroline Semaille, Thomas Volpe, Jacques Cadranel, Thomas Gorget, Julien Saussereau, Elodie Issorat, Sami Kolta, Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-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)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Réanimation Médicale et Toxicologique [Hôpital Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Porcher, Raphaël

Subjects
Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, Randomized controlled trial, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Hazard ratio, Articles, Middle Aged, Intensive care unit, Hospitals, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Hospitalization, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Treatment Outcome, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Critical Care, Population, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, Humans, education, Critical Care Outcomes, Aged, Mechanical ventilation, Anakinra, SARS-CoV-2, business.industry, Comment, COVID-19, Bayes Theorem, Pneumonia, medicine.disease, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Interleukin 1 Receptor Antagonist Protein, 030228 respiratory system, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, business, Interleukin-1
Abstract

International audience; Background: Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods: In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual.Findings: Between April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2·5%, 90% credible interval [CrI] -17·1 to 12·0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61·2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54·5% (median posterior HR 0·97; 90% CrI 0·62 to 1·52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usual care group (p=0·45).Interpretation: Anakinra did not improve outcomes in patients with mild-to-moderate COVID-19 pneumonia. Further studies are needed to assess the efficacy of anakinra in other selected groups of patients with more severe COVID-19.Funding: The Ministry of Health, Programme Hospitalier de Recherche Clinique, Foundation for Medical Research, and AP-HP Foundation.

Published
2021
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49. Interleukin 6 receptor inhibition in primary Sjögren syndrome: a multicentre double-blind randomised placebo-controlled trial

Author

Christophe Richez, S. Rist, Christelle Sordet, Valérie Devauchelle-Pensec, Aleth Perdriger, Jacques Morel, Azeddine Dellal, Claire Larroche, Alain Saraux, Carine Salliot, Arsène Mekinian, Raphaèle Seror, Philippe Dieudé, Jean Sibilia, David Saadoun, Thierry Martin, Renaud Felten, Eric Hachulla, Charles Zarnitsky, Emanuelle Dernis, A. Contis, P. Kieffer, Patrice Cacoub, Jean-Marie Berthelot, Mira Y Tawk, Olivier Vittecoq, Lise Holterbach, Ouafaa Aberkane, Véronique Le Guern, Gilles Blaison, Nicolas Meyer, Cécile Arnold, Emmanuel Chatelus, François Maurier, Hatron Pierre Yves, Emmanuel Andrès, Pierre Duffau, Xavier Mariette, Jacques-Eric Gottenberg, Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de médecine interne et maladies infectieuses [Bordeaux], CHU Bordeaux [Bordeaux]-Groupe hospitalier Saint-André, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional d'Orléans (CHRO), CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de médecine interne [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, CHU Strasbourg, Groupe Hospitalier du Havre Hôpital Jacques Monod (MONTIVILLIERS) (GHH), CH Colmar, Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Hôpital Sainte Blandine, Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), CHU Saint-Antoine [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
medicine.medical_specialty, Immunology, Population, Placebo-controlled study, Placebo, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Double blind, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Tocilizumab, Double-Blind Method, Rheumatology, Internal medicine, medicine, Clinical endpoint, Humans, Immunology and Allergy, 030212 general & internal medicine, 10. No inequality, education, Primary Sjögren Syndrome, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Middle Aged, Receptors, Interleukin-6, cytokines, 3. Good health, chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Sjogren's syndrome, biological therapy, Interleukin-6 receptor, Female, business
Abstract

ObjectivesNo immunomodulatory drug has been approved for primary Sjögren’s syndrome, a systemic autoimmune disease affecting 0.1% of the population. To demonstrate the efficacy of targeting interleukin 6 receptor in patients with Sjögren’s syndrome-related systemic complications.MethodsMulticentre double-blind randomised placebo-controlled trial between 24 July 2013 and 16 July 2018, with a follow-up of 44 weeks, involving 17 referral centres. Inclusion criteria were primary Sjögren’s syndrome according to American European Consensus Group criteria and score ≥5 for the EULAR Sjögren’s Syndrome Disease activity Index (ESSDAI, score of systemic complications). Patients were randomised to receive either 6 monthly infusions of tocilizumab or placebo. The primary endpoint was response to treatment at week 24. Response to treatment was defined by the combination of (1) a decrease of at least 3 points in the ESSDAI, (2) no occurrence of moderate or severe activity in any new domain of the ESSDAI and (3) lack of worsening in physician’s global assessment on a Visual Numeric Scale ≥1/10, all as compared with enrolment.Results110 patients were randomised, 55 patients to tocilizumab (mean (SD) age: 50.9 (12.4) years; women: 98.2%) and 55 patients to placebo (54.8 (10.7) years; 90.9%). At 24 weeks, the proportion of patients meeting the primary endpoint was 52.7% (29/55) in the tocilizumab group and 63.6% (35/55) in the placebo group, for a difference of −11.4% (95% credible interval −30.6 to 9.0) (Pr[Toc >Pla]=0.14).ConclusionAmong patients with primary Sjögren’s syndrome, the use of tocilizumab did not improve systemic involvement and symptoms over 24 weeks of treatment compared with placebo.Trial registration numberNCT01782235.

Published
2021
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50. Hunting for the genetic basis of Susac syndrome

Author

Philippe Dieudé, Caroline Kannengiesser, Boris Keren, Catherine Boileau, Karim Sacre, Ibrahima Ba, Emmanuelle Ollivier, Thomas Papo, and C. David

Subjects
Genetics, Diagnosis, Differential, Susac Syndrome, Neurology, business.industry, Medicine, Humans, Neurology (clinical), business, Magnetic Resonance Imaging
Published
2021

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