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Several studies have suggested that obesity could have a negative effect on response to anti-tumor necrosis factor α (anti-TNFα) in rheumatoid arthritis (RA). Little is known about the impact of body mass index (BMI) on other biologic agents. We aimed to evaluate the effect of BMI on response to tocilizumab (TCZ) in RA. RA patients treated with TCZ were included in this multicenter retrospective study. BMI was calculated at the initiation of treatment. After 6 months of treatment, change from baseline in DAS28, pain on a visual analog scale, erythrocyte sedimentation rate and C-reactive protein level, and tender and swollen joints were analyzed. The primary endpoint was decrease in DAS28 ≥ 1.2. Secondary outcomes were good response and remission by EULAR criteria. At baseline, among 115 RA patients included, the median (interquartile range) BMI was 25.4 (22.0-28.8) kg/m(2). The number of patients with normal weight, overweight, and obesity was 53 (46 %), 37 (32 %), and 25 (22 %), respectively. Baseline characteristics did not differ between the three subgroups of BMI. The median BMI did not differ between responders and non-responders for DAS28 decrease ≥1.2 (25.7 [22.1-29.9] vs 24.9 [22.0-27.1], P = 0.38), EULAR good response (25.9 [22.8-30.0] vs 25.4 [22.0-28.4], P = 0.61), and remission (25.1 [22.5-28.6] vs 25.4 [22.0-28.9], P = 0.76). BMI did not affect the response to TCZ in RA. If confirmed, these results could be helpful for the selection of a biologic agent in obese RA patients.

Background The optimal treatment for patients with severe coronavirus-19 disease (COVID-19) and hyper-inflammation remains debated. Material and methods A cohort study was designed to evaluate whether a therapeutic algorithm using steroids with or without interleukin-1 antagonist (anakinra) could prevent death/invasive ventilation. Patients with a ≥5-day evolution since symptoms onset, with hyper-inflammation (CRP≥50mg/L), requiring 3–5 L/min oxygen, received methylprednisolone alone. Patients needing ≥6 L/min received methylprednisolone + subcutaneous anakinra daily either frontline or in case clinical deterioration upon corticosteroids alone. Death rate and death or intensive care unit (ICU) invasive ventilation rate at Day 15, with Odds Ratio (OR) and 95% CIs, were determined according to logistic regression and propensity scores. A Bayesian analysis estimated the treatment effects. Results Of 108 consecutive patients, 70 patients received glucocorticoids alone. The control group comprised 63 patients receiving standard of care. In the corticosteroid±stanakinra group (n = 108), death rate was 20.4%, versus 30.2% in the controls, indicating a 30% relative decrease in death risk and a number of 10 patients to treat to avoid a death (p = 0.15). Using propensity scores a per-protocol analysis showed an OR for COVID-19-related death of 0.9 (95%CI [0.80–1.01], p = 0.067). On Bayesian analysis, the posterior probability of any mortality benefit with corticosteroids+/-anakinra was 87.5%, with a 7.8% probability of treatment-related harm. Pre-existing diabetes exacerbation occurred in 29 of 108 patients (26.9%). Conclusion In COVID-19 non-ICU inpatients at the cytokine release phase, corticosteroids with or without anakinra were associated with a 30% decrease of death risk on Day 15.

Introduction La pneumopathie interstitielle diffuse (PID) est une manifestation extra-articulaire frequente de la polyarthrite rhumatoide (PR) associee a une forte morbi-mortalite. La prevalence exacte de la PR-PID clinique ou infraclinique varie ainsi selon les etudes entre 20 et 60 % et depend de la methode de depistage et de sa temporalite par rapport au debut de la PR. Recemment, le variant du promoteur de MUC5B rs35705950 a ete associe a la presence d’une PID chez les patients atteints de PR. La cohorte ESPOIR a inclus et suivi des patients âges de 18 a 70 ans souffrant d’une PR recente probable ou certaine. Nos objectifs etaient : – d’estimer la prevalence de la PID infraclinique au sein de la cohorte ESPOIR apres au moins 10 ans d’evolution ; – d’evaluer l’interet du genotypage de MUC5B rs35705950 comme marqueur predictif de survenue d’une PR-PID. Patients et methodes Dans cette etude transversale au sein de la cohorte ESPOIR, un depistage d’une PID par scanner thoracique haute-resolution (HRCT) a ete systematiquement propose aux patients inclus dans ESPOIR apres 13 ans de suivi. Une lecture centralisee des HRCT a ete realisee par un radiologue expert qui a classe les patients en fonction de la presence ou l’absence de PID. En cas de PID, l’extension et l’aspect ont ete evalues. Deux patients issus de la cohorte ESPOIR precedemment decedes d’une PR-PID ont ete inclus dans l’analyse afin d’identifier les facteurs prognostiques. Tous les patients inclus ont ete genotypes pour MUC5B rs35705950. Une regression logistique a ete utilisee afin d’identifier les facteurs collectes a l’inclusion dans ESPOIR et predictifs de la presence d’une PID apres au moins 10 ans d’evolution de la PR. Les intervalles de confiance ont ete estimes par methode d’echantillonnage. Resultats Parmi les 170 patients explores par HRCT [133 femmes (78,2 %), duree moyenne de la PR 13,7 ± 1,1 ans], une PID infraclinique etait detectee chez 31 patients (18,2 %) : 19 femmes (61,3 %), âge moyen 67,9 ± 8,7 ans, âge moyen au diagnostic de PR 54,3 ± 8,6 ans. L’etendue de la PID etait 10 % chez 9 patients (5,3 %). Quatre patients presentaient un aspect de pneumopathie interstitielle commune, 4 patients presentaient un aspect de pneumopathie interstitielle non specifique. Des signes scannographiques de fibrose pulmonaire etaient detectes chez 16 patients (9,4 %). Parmi les europeens caucasiens (n = 160), la frequence de l’allele mineur de MUC5B rs35705950 etait de 26,5 % chez les patients PR-PID et de 8,9 % chez les patients PR-non PID (OR = 6,0 ; IC95 %(1,2–7,2)). Apres regression logistique, les facteurs presents au diagnostic de PR et predictifs de survenue d’une PID a 13 ans etaient le sexe masculin (OR = 2,6 IC95 %(1,0-6,6)), un âge au debut de la PR > 49 ans (OR = 5,2 IC95 %(2,0-15,1)), un nombre d’articulations gonflese >9 (OR = 2,9 IC95 %(1,2-7,2)), le caractere migrateur et non fixe des arthrites (OR = 3,4 IC95 %(1,4-8,7)) et l’allele a risque T de MUC5B rs35705950 (OR = 3,8 IC95 %(1,5-10,1)). Ce modele logistique permettait de predire la presence d’une PID apres au moins 10 ans d’evolution de la PR avec une aire sous la courbe = 0,80 IC95 %(0,72-0,90). Conclusion Dans la cohorte ESPOIR, apres au moins 10 ans d’evolution de la PR, la prevalence de la PID infraclinique etait de 18,2 %. Au diagnostic de PR, en association avec certaines donnees cliniques, le genotypage de MUC5B rs35705950 permet d’ameliorer la stratification des patients a risque de developper ulterieurement une PID.

Introduction L’existence d’un antecedent familial de polyarthrite rhumatoide (PR) constitue l’un des principaux facteurs de risque de developper la maladie. Plusieurs etudes conduites chez des patients presentant une PR etablie ont montre une association entre la presence d’un antecedent familial de PR et certaines caracteristiques de la maladie telles que le statut serologique, l’âge de debut et possiblement le profil de reponse a certains des traitements de fond de la maladie. A ce jour, l’impact d’un antecedent familial de PR dans le contexte particulier de la polyarthrite debutante n’a pas ete etudie. L’objectif de cette etude ancillaire de la cohorte ESPOIR etait de determiner, chez des patients presentant une polyarthrite debutante, l’impact d’un antecedent familial de PR sur la presentation initiale du rhumatisme inflammatoire, le diagnostic final et le devenir a long terme de la pathologie. Patients et methodes Cette etude a ete conduite chez l’ensemble des patients inclus dans la cohorte ESPOIR entre 2002 et 2005. Dans le cadre de cette cohorte prospective, des patients âges de 18 a 70 ans ont ete recrutes sur la base de la presence d’au moins 2 articulations gonflees depuis plus de 6 semaines et moins de 6 mois, l’absence d’utilisation prolongee de la corticotherapie et l’absence de recours prealable a un traitement de fond antirhumatismal. De plus, le diagnostic de PR devait etre considere comme certain ou probable par le rhumatologue referent. Dans le cadre de cette etude ancillaire, les patients ont ete stratifies en deux groupes selon l’identification d’un antecedent familial de PR lors de l’evaluation systematique a la visite d’inclusion. Les donnees concernant la presentation initiale du rhumatisme inflammatoire, le diagnostic final (avec un recul de 2 ans) et l’evolution a long terme (a 5 ans) ont ete comparees entre les deux groupes de patients. Les analyses statistiques ont ete realisees a l’aide du logiciel SPSS, ajustees sur les facteurs de confusion potentiels pour ce qui concerne les variables dichotomiques relatives au devenir des patients. Resultats Cent quinze patients (14,1 %) ont rapporte un antecedent familial de PR. En ce qui concerne la presentation initiale du rhumatisme inflammatoire les patients ayant rapporte un antecedent familial de PR presentaient de facon plus frequente des manifestations extra-articulaires (51,8 % versus 39,6 %, p = 0,01). En ce qui concerne le diagnostic final, les patients ayant rapporte un antecedent familial avaient de facon moins frequente un diagnostic alternatif plausible a la PR d’apres le rhumatologue referent (28,3 % versus 42,1 %, p-ajuste = 0,02). En ce qui concerne le devenir a long terme, le recours a un traitement de fond biologique etait plus frequent chez les patients ayant rapporte un antecedent familial (24,7 % versus 14,8 %, p-ajuste = 0,02), donnees etayees par des analyses supplementaires de survie. Conclusion Cette etude demontre que dans le contexte de la polyarthrite debutante, l’identification d’un antecedent familial de PR constitue une donnee cliniquement pertinente, contenant des informations en rapport avec la certitude diagnostique et l’indication future a un traitement de fond biologique.

Introduction La pseudopolyarthrite rhizomelique (PPR) est un rhumatisme inflammatoire survenant apres 50 ans avec un pic de frequence entre 70 et 80 ans. La TEP-TDM au 18F-FDG n’est pas recommandee en cas de PPR isolee mais est utile pour rechercher une arterite a cellules geantes associee ou en cas de doute sur l’existence d’une forme paraneoplasique. Les spondylarthropathies (SPA) touchent classiquement le sujet jeune, avant l’âge de 45 ans. La TEP-TDM n’a pas d’indication dans la SPA de presentation classique. Neanmoins, on estime que 3,5 % des SPA surviennent apres l’âge de 50 ans. Ces SPA de debut tardif constituent un challenge pour le clinicien, car elles ont une presentation clinique atypique. L’objectif de cette etude est d’evaluer l’interet de la TEP-TDM pour discriminer PPR et SPA a debut tardif en pratique clinique. Patients et methodes Afin d’identifier les patients atteints de PPR et SPA, nous avons conduit une recherche dans la base de donnees de 2 services de rhumatologie. Le diagnostic de PPR ou de SPA etait pose par des cliniciens experimentes. La lecture de la TEP-TDM etait effectuee par 2 medecins nucleaires en aveugle des donnees cliniques. Resultats Nous avons inclus 62 patients entre septembre 2012 et aout 2018. Trente-cinq patients avaient une PPR (56,5 %) et 27 une SPA (43,5 %). Les caracteristiques des patients sont presentees dans le Tableau 1 . L’hypermetabolisme en TEP-sur les entheses etait environ 2 fois plus frequent chez les patients PPR, particulierement au niveau rachidien (processus epineux 88,6 vs 40,7 %, p Tableau 1 ). L’intensite de l’hypermetabolisme des entheses ne permettait pas de discriminer PPR et SPA. Un score cumulatif d’hyperfixation enthesitique est en cours de construction pour permettre de differencier PPR et SPA a debut tardif. Nous n’avons pas observe de difference de frequence d’hypermetabolisme sur les articulations, les vaisseaux ni les muscles. Conclusion Cette etude montre que l’hypermetabolisme des entheses se rencontre aussi bien au cours de la SPA que de la PPR mais est plus frequente dans cette derniere population, essentiellement au niveau du rachis, des hanches et des epaules. Des analyses complementaires sont en cours pour la recherche d’un score musculosquelettique permettant de discriminer les 2 pathologies en cas de presentation atypique comme c’est le cas chez les SPA a debut tardif.

Background: Methotrexate (MTX) is a key anchor drug for rheumatoid arthritis (RA) management. Its use has been associated with hypersensitivity pneumonitis and diffuse lung disease. Whether MTX exposure increases the risk of interstitial lung disease (ILD) in patients with RA is disputed. Objectives: We aimed to evaluate the association of antecedent MTX use with development of RA-ILD. Methods: Through a case-control study design with derivation and international validation samples, we examined the association of MTX exposure with ILD in 482 patients with RA-ILD and 741 patients with RA without ILD. Estimates were pooled over the different samples using meta-analysis techniques. Results: Analysis of the derivation sample revealed an inverse relationship between MTX exposure and RA-ILD (adjusted odds ratio [OR], 0.48; 95% confidence interval [CI], 0.25 to 0.92; P=0.028), which was confirmed in the validation samples (pooled adjusted OR, 0.39; 95% CI, 0.23 to 0.68; P Conclusion: Our results suggest that MTX is not a risk factor for RA-ILD and support a possible disease modifying effect of MTX on development of RA-ILD. Disclosure of Interests: Pierre-Antoine Juge: None declared, Joyce S. Lee Consultant of: Celgene, Genentech, Boehringer Ingelheim, Jessica Lau: None declared, Leticia Kawano: None declared, Jorge Rojas-Serrano: None declared, Marco Sebastiani: None declared, Gouri Koduri: None declared, Eric Matteson Grant/research support from: Pfizer, Consultant of: Boehringer Ingelheim, Gilead, TympoBio, Arena Pharmaceuticals, Speakers bureau: Simply Speaking, Karina Bonfiglioli Consultant of: Roche, Abbvie, Pfizer, Janssen and BMS, Marcio Sawamura: None declared, Ronaldo Kairalla: None declared, Lorenzo Cavagna: None declared, Emanuele Bozzalla Cassione: None declared, Andreina Manfredi: None declared, Mayra Mejia: None declared, Pedro Rodriguez Henriquez: None declared, Montserrat I. Gonzalez-Perez: None declared, Ramces Falfan-Valencia: None declared, Ivette Buendia-Roldan: None declared, Glora Perez-Rubio: None declared, Esther Ebstein Consultant of: BMS, Employee of: BMS, Steven Gazal: None declared, Raphael Borie Consultant of: Roche, Boehringer Ingelheim, Sebastien Ottaviani: None declared, Caroline Kannengiesser: None declared, Benoit Wallaert Consultant of: Roche, Boehringer Ingelheim, Yurdagul Uzunhan Consultant of: Roche, Boehringer Ingelheim,, Hilario Nunes: None declared, Dominique Valeyre Consultant of: Astra Zeneca, Roche, Boehringer Ingelheim, Nathalie Saidenberg Kermanac’h: None declared, marie-Christophe Boissier: None declared, Lidwine Wemeau Stervinou Consultant of: Roche, Janssen, BMS, Boehringer Ingelheim, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Sylvain Marchand-Adam Consultant of: Roche, Novartis, Boehringer Ingelheim, Pascal Richette: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi, Claire Dromer: None declared, Marie-Elise Truchetet: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thierry Schaeverbeke: None declared, Huguette Liote: None declared, Gabriel Thabut Employee of: Astra Zeneca, Kevin Deane Grant/research support from: Janssen, Consultant of: Inova, ThermoFisher, Janseen, BMS and Microdrop, Joshua Solomon: None declared, Tracy Doyle: None declared, Jay H. Ryu: None declared, Ivan O. Rosas Consultant of: Boehringer Ingelheim, Gerentech, Three Lakes Partners, V. Michael Holers Grant/research support from: Janssen, Celgene, and BMS, Catherine Boileau: None declared, Marie-Pierre Debray: None declared, Raphael Porcher: None declared, David A. Schwartz Consultant of: NuMedii, Robert Vassallo Shareholder of: Pfizer, BMS, SunPharma, Bruno Crestani Shareholder of: Apellis, Boehringer Inghelheim, Medillune, Roche, Consultant of: Boehringer Ingelhiem, Astra Zeneca, Roche, Sanofi, Philippe Dieude: None declared

Objectives:Secukinumab (SEC) is an interleukin-17 inhibitor used to treat patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Drug maintenance is often used as a proxy for treatment effectiveness and safety in real life settings. We aim to assess SEC maintenance in routine clinical practice and to identify survival predictors associated.Methods:We conducted a retrospective, longitudinal, observational, multicenter study including all patients (pts) with axSpA or PsA who received at least 1 injection of SEC between July 2016 and October 2019. We collected patient’s demographics and clinic characteristics, SEC date of initiation and dosage and dosage modification of SEC, previous biologic Disease-modifying antirheumatic drugs (bDMARDs) and concomitant treatments. Date and reasons of discontinuation – i.e., lack of efficacy, safety issue, sustained remission or others – were collected. Several potential maintenance predictors were tested: age, gender, disease (axSpA or PsA), smoking status, bDMARDs history and concomitant treatment. Among patients with non-radiographic axSpA (nr-axSpA), evidence of MRI sacroiliitis or elevated CRP were also assessed as potential maintenance predictors. Drug maintenance was analyzed by the Kaplan-Meier method and adjusted for baseline factors were estimated by log rank analysis.Results:The main characteristics of the 561 pts included were the following: 363 (64.7%) axSpA, 198 (35.3%) PsA, 329 (58.6%) female, mean age 45,6 +/- 12 years, 221 (39.4%) smokers, 175 (31.2%) radiographic sacroiliitis, 259 (46.2%) MRI sacroiliitis, 198 (35.3%) elevated CRP, 247 (44.0%) HLA B27 positive, mean BASDAI 48,3 +/- 26.8%. SEC was associated to methotrexate (MTX) in 139 pts (24.8%) and was the first line bDMARD in 55 pts (9.8%). The median drug maintenance (MDM) of SEC was 79 weeks (wk) [73-84]. At 52 wk, 245 pts (60%) SpA were still treated with SEC. During the 3-year follow-up, 264 pts discontinued SEC: 180 (68.2%) pts for lack of effectiveness, 47 (17.8%) for adverse events, 14 (5.3%) for others and 23 (8.7%). SEC prescription as first line bDMARD was associated with longer survival versus second line or more: 111 wk [83-138] vs. 69 wk [57-80] (p=0. 017) (figure 1). MDM was not significantly different depending on gender, MTX combo, elevated CRP, axSpA vs PsA and smoking status. Among the nr-axSpA pts, MRI sacroiliitis or elevated CRP did not modify SEC maintenance (p=0.68) (figure 2).Figure 1.Secukinumab maintenance according to therapeutic lineFigure 2.Secukinumab maintenance in nr-axSpA populationConclusion:In routine clinical practice, SEC median maintenance was 79 weeks. Fist line administration was the only independent factor associated with improved SEC retention. Lack of effectiveness was the most common reason of discontinuation.Disclosure of Interests:Benoît Flachaire: None declared, Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Vincent Pradel: None declared, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Guy Baudens: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Corinne Miceli Richard: None declared, Philippe Dieudé: None declared, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Jérémie SELLAM: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Marie-Hélène Guyot: None declared, Chi Duc Nguyen: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly, Thao Pham Speakers bureau: Novartis, Janssen, Lilly

Background:Real-world data are missing for Ustekinumab (UST) and secukinumab (SEK) in psoriatic arthritis (PsA).Objectives:To evaluate the characteristics of the patients (pts) with PsA treated by UST or SEK and to assess real world persistence of UST and SEK in PsA.Methods:This is a retrospective, multicenter study of pts with PsA (CASPAR criteria or diagnosis confirmed by a rheumatologist) initiating UST or SEK with a follow-up ≥ 6 months from January 2011 to April 2019. The comparison of persistence between UST and SEK was analysed using a Cox model with an inverse probability of treatment weighting propensity score including 11 confounding factors. Subgroup analyses (age>65 years, gender, Body Mass Index (BMI), Charlson score>2, psoriasis, CRP>5mg/L, number (nb) of prior biotherapies, proportion of pts on maximum dose of UST or SEK, combination with methotrexate (MTX), enthesitic and axial forms of PsA) were also performed to test the heterogeneity of UST and SEK persistence. Finally, 2 sensitivity analyses were performed, first excluding the pts treated before the marketing authorization of SEK, and then excluding the pts that underwent a molecule switch. Causes of discontinuation were also collected.Results:406 pts were included: 245 with UST and 161 with SEK. At baseline before propensity score-matching, the UST group has a higher BMI (28.9 ± 6.4 kg/m2vs. 27.4 ± 6.0 kg/m2), more peripheral forms (98% vs. 90.8%), a higher nb of active smokers (27.1% vs. 19.9%), a higher frequency of psoriasis (96.3% vs. 83.2%), less MTX users (38.9% vs. 44.2%), a higher nb of pts with CRP >5mg/L (54.3% vs. 47%), a higher nb of pts naïve to biotherapies (22% vs. 13%) and a higher nb of pts with recommended dosing (97.3% vs 50.9%). The median persistence was 9.4 months and 14.7 months for UST and SEK, respectively. The persistence rate was lower in the UST group compared to the SEK group (40.9% vs. 59.1% % at 1 year; 26.4% vs. 38.0% at 2 years; weighted HR=1.42; 95% CI 1.07 to 1.92; p=0.015) (Fig 1). In subgroup analysis, combination with MTX was associated with a higher persistence rate in the patients with SEK compared to those receiving UST: 43.6% vs. 23.2% (HR=2.20; 95% CI 1.30 to 3.51; p=0.001), whereas no difference was observed in SEK and UST monotherapy: 33.8% vs 28.4%, respectively (HR=1.06; 95% CI 0.74 to 1.53; p=0.75) (Fig 2). A similar difference was found in the sensitivity analyses, with however a difference at the limit of significance for the analysis excluding pts with a molecule switch (adjusted HR=1.35; IC95% 0.96 to 1.92; p=0.085). The causes of discontinuation were due to inefficacy in 85% of cases and an adverse event in 12% of cases (19% in the SEK group and 9% in the UST group).Conclusion:In this first real-world study comparing UST and SEK persistence in PsA, the persistence of SEK was longer than that of UST. Subgroup analysis revealed this difference of persistence was restricted to patients treated in combination with MTX.Disclosure of Interests:Jean-Guillaume Letarouilly Grant/research support from: Research grant from Pfizer, Benoît Flachaire: None declared, Céline Labadie: None declared, Nicolas Cohen Speakers bureau: Novartis, Janssen, Maeva Kyheng: None declared, Jérémie SELLAM: None declared, Pascal Richette: None declared, Philippe Dieudé: None declared, Pascal Claudepierre Speakers bureau: Janssen, Novartis, Lilly, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB, Eric Houvenagel Speakers bureau: Janssen, Novartis, Chi Duc Nguyen: None declared, Marie-Hélène Guyot: None declared, Nicolas Segaud: None declared, Frederic Maury: None declared, Laurent Marguerie: None declared, Xavier Deprez Speakers bureau: Novartis, Janssen, Jean-Hugues Salmon Speakers bureau: Novartis, Janssen, Guy Baudens: None declared, Corinne Miceli Richard: None declared, Elisabeth Gervais Speakers bureau: Novartis, Janssen, Roche, Pfizer, BMS, Abbvie, Isabelle CHARY VALCKENAERE: None declared, Pierre Lafforgue Speakers bureau: Novartis, Janssen, Damien LOEUILLE: None declared, Christophe Richez Consultant of: Abbvie, Amgen, Mylan, Pfizer, Sandoz and UCB., Thao Pham Speakers bureau: Novartis, Janssen, Lilly, Rene-Marc Flipo Speakers bureau: Novartis, Janssen, Lilly

Background:Cutaneous involvement is common during primary Sjogren’s Syndrome (pSS) but prevalence and characteristics are difficult to establish precisely because of the limited number of patients studied in most cohorts, the variability of the disorders evaluated in each cohort, the rarity of some of them, and the heterogeneity of evaluations from previous studies (1).Objectives:To determine the prevalence and significance of dermatological disorders in primary Sjogren Syndrome.Methods:We use 2 French cohorts (ASSESS, in which prevalence of skin disorders in 395 pSS patients was evaluated, and diapSS in which 91 consecutive pSS patients had an examination by a dermatologist) and baseline data of the TEARS randomized trial (110 patients with recent or active pSS, treated with rituximab or placebo, and evaluated for skin dryness using a visual analogue scale out of 100).Results:Skin manifestations included in the ESSDAI were rare in the ASSESS cohort (n=16/395, 4.1%, mainly purpuras; only 3 had high activity) but associated with activity in the other ESSDAI domains (peripheral neurological (p50; 48.2%) and that these dry skin patients had higher pain VAS (61.5+/-28.2 vs 46.8+/-27.0; p=0.003) and drought (79.4+/-15.2 vs 62.5+/-21.7; pCutaneous involvementNo Cutaneous involvementTotalp values*Muscular3/16 (18.8)10/373 (2.7)13/389 (3.3)0.001Peripheral nervous system PNS4/16 (25)34/373 (9.1)38/389 (9.8)0.00001Biological8/16 (50)138/371 (37.2)146/387 (37.7)0.017Hematologic7/16 (43.8)55/373 (14.7)62/389 (15.9)0.017History of arthritis12/16 (75)154/374 (41.2)166/390 (42.6)0.008History of splenomegaly2/16 (12.5)10/3762.7)12/392 (3.1)0.024History of lymphoma0/16 (0)18/379 (4.7)18/395 (4.6)0.372Mean (SD) ESSDAI score14.5 (6.8)4.4 (5.1)0.00001Mean (SD) ESSDAI score after excluding the points awarded by skin manifestations8.1 (6.2)4.4 (5.1)0.014Gammaglobulin levels (mean +/- SD)23.1 +/-7.318.5 +/-8.1-0.006Conclusion:The most common skin disorder is dryness, which is associated with a higher level of pain and overall subjective dryness. ESSDAI skin activity is rare, associated with hypergammaglobulinemia and ESSDAI activity. Systematic dermatological examination is informative for non-specific pSS lesionsReferences:[1]Orgeolet L, Foulquier N, Misery L, Redou P, Pers J-O, Devauchelle-Pensec V, et al. Can artificial intelligence replace manual search for systematic literature? Review on cutaneous manifestations in primary Sjögren’s syndrome. Rheumatol Oxf Engl. 2019 Aug 31;Disclosure of Interests:Camille Villon: None declared, Laure Orgeolet: None declared, Anne-Marie Roguedas-Contios: None declared, Laurent Misery: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Divi Cornec: None declared, Sandrine Jousse-Joulin: None declared, Raphaèle Seror Consultant of: BMS UCB Pfizer Roche, Jean-Marie Berthelot: None declared, Philippe Dieudé: None declared, Jean-Jacques Dubost: None declared, anne-laure Fauchais: None declared, Vincent Goeb: None declared, Eric Hachlla: None declared, Pierre-Yves Hatron: None declared, Claire Larroche: None declared, Gilles Hayem: None declared, Véronique LE GUERN Grant/research support from: UCB for GR2 study (to our institution), Aleth Perdriger: None declared, Jacques Morel: None declared, Olivier VITTECOQ: None declared, Xavier Mariette Consultant of: BMS, Gilead, Medimmune, Novartis, Pfizer, Servier, UCB, Valerie Devauchelle-Pensec: None declared, alain saraux: None declared

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, pConclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

Asbestosis is a fibrosing interstitial pneumonitis, which can develop following occupational asbestos exposure and a lengthy latency period [1]. Even after strict regulations on the asbestos industry, an estimated 3400 individuals worldwide died as a consequence of asbestosis in 2017 [2]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr Platenburg has nothing to disclose. Conflict of interest: Dr Wiertz has nothing to disclose. Conflict of interest: Dr van der Vis has nothing to disclose. Conflict of interest: Dr Crestani has nothing to disclose. Conflict of interest: Dr Borie reports grants and personal fees from Roche, grants and personal fees from Boerhinger Ingelheim, outside the submitted work. Conflict of interest: Philippe Dieude Conflict of interest: Dr Kannengiesser has nothing to disclose. Conflict of interest: D. Burgers reports grants from MSD, other from Roche, other from AstraZeneca, other from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Grutters has nothing to disclose. Conflict of interest: Dr van Moorsel has nothing to disclose.

Background We aimed to compare the efficacy of steroids alone or associated with immunosuppressive drugs for the prevention of relapse in cardiac sarcoidosis (CS). Methods In this monocentric multidisciplinary retrospective single center study, all consecutive patients with histologically proven sarcoidosis hospitalized from January 2012 to December 2016 were considered. All patients with symptomatic CS were studied. Patients received steroids or steroids plus immunosuppressive drugs (IS) for CS treatment at diagnosis. The efficacy of each treatment strategy (steroids vs steroids + IS) was assessed by the cardiac relapse rate over follow up. Results 326 consecutive patients with histologically proven sarcoidosis were screened. Among them, 36 (11%) had symptomatic CS (20 (55.5%) men, median age at diagnosis 48.5 [22.8–76]). Twenty-four patients received steroids and 12 received steroids + IS (azathioprine n = 5, methotrexate n = 5, cyclophosphamide n = 2) at CS diagnosis. Over a median follow up of 3.6 [1–15.2] years, 13 (36.1%) patients suffered a cardiac relapse including reduced left ventricular ejection fraction (LVEF, n = 4), third degree heart block (n = 2), atrio-ventricular (n = 1) or ventricular (n = 1) tachycardia and sudden cardiac death (n = 1). Except for a higher frequency of black patients in patients receiving IS, CS features at diagnosis and median time to relapse did not significantly differ between patients who did or did not receive IS. Relapse rate was 45.8% in the steroids group versus 16.7% in the steroids + IS group (p = 0.048). Conclusions In cardiac sarcoidosis, the combination of steroids with immunosuppressive drugs might reduce the risk of cardiac relapse, as compared to steroids alone.

Genetic testing is proposed for suspected cases of pulmonary fibrosis of genetics origin but clinicians and patients need advice about the related diagnostic and management issues. Because multidisciplinary team (MDT) has been shown to improve accuracy of ILD diagnosis, we evaluated the feasibility of an MDT dedicated to the indication and interpretation of genetic testing. The MDT met monthly, included pneumologists experts in ILD in adults, children, geneticists, radiologist. Hematologists, rheumatologists, dermatologists, hepatologists, and pathologists were also invited to attend. Since 2016, 70 patients (37 males, 33 females) were discussed, from 31 different centers (7 countries). Mean age was 46.4 years [0-71] including 3 patients The MDT therapeutic proposals were: antifibrotic drugs (n=23), best supportive care (n=4), surgical lung biopsy (n=2), steroids (n=7), lung transplantation (n=16), or watch and wait (n=9). Our experience shows that a dedicated MDT with genetic analysis is feasible including patients of all ages and provides a unique opportunity to improve knowledge and to adapt patient management and therapy.

Background Myositis prevalence in primary Sjogren’s syndrome (pSS) and whether it is associated with peculiar extra-muscular involvement and/or a biological profile is unknown. Objectives To refine prevalence and characteristics of patients with pSS and myositis. Methods In the national multicenter prospective cohort ASSESS (395 patients with pSS with a 5 year-prospective follow-up), patients with suspected myositis were identified. Their charts were reviewed and the patients were compared with the rest of the cohort. Results Myositis was suspected in 38 patients (2 men, 36 women, 5829–78 yr old) because of myalgia and/or exercise intolerance (n=38) along with high blood CK level (n=28). As compared with the rest of the cohort, they had higher patient-reported signs including pain VAS, dryness VAS and patient reported index ESSPRI (6.3 vs 5.3, p=0.007). In contrast, proportion of systemic involvements (76.3% vs 70.9%, p=0.57) and systemic disease activity measured by the ESSDAI, without taking the muscular domain into account (2 vs 3, p=0.93), were not different from patients without suspected myositis. Demographic characteristics and disease duration were also similar. Electromyographic recording and/or muscle histology performed in these 38 patients objective muscular involvement in only 4 patients (1% of the cohort). - Three patients were diagnosed with inclusion body myositis (sIBM). Accordingly, age at first sign was 49 years,49–60 muscle disease had progressive onset as suggested by the 11 years1–28 delay between first muscle sign and diagnosis. CK level was - One pSS patient with myositis was a 39 years old woman with polymyositis. She developed proximal muscle weakness, CK was 750UI/L and muscle biopsy found endomysial infiltrate. Muscle force and CK level normalised with immunomodulatory drugs. Compared to the rest of the cohort, patient with myositis had longer disease duration at inclusion (15 vs 5 year, p=0.01) and tended to be younger at pSS diagnosis (41.5 vs 53 year, p=0.07). They had more frequent history of systemic manifestations (100% vs 65.0%, p=0.011) but ESSDAI at baseline (2 vs 3, p=0.56) and the biological characteristics were not different from patients without myositis. In contrast with the patients with suspected but not confirmed myositis, patient-reported signs (i.e. fatigue, pain, dryness and ESSPRI score) were similar to patients without myositis. Conclusions Myositis is frequently suspected in patients with pSS, especially when patients-reported signs are particularly disabling. Myositis occurs very infrequently (1% of the cohort), in patients with longer disease duration. sIBM was the most predominant subset of myositis in the present study. Disclosure of Interest None declared

Resume Objectif Les doses maximales de l’allopurinol sont limitees en cas d’insuffisance renale chronique, particulierement aux stades 4/5. Le febuxostat possede un metabolisme hepatique et son utilisation a ete autorisee sans modification posologique chez les patients insuffisants renaux stades 1 a 3. Notre objectif etait d’etudier la tolerance et l’efficacite du febuxostat chez les patients insuffisants renaux chroniques stades 4/5. Methodes Dans cette etude retrospective, nous avons inclus les patients presentant (1) un diagnostic de goutte, (2) un traitement par febuxostat, (3) un debit de filtration glomerulaire ≤ 30 mL/min/1,73m 2 (formule MDRD) lors de l’initiation du febuxostat et (4) un suivi d’au moins 3 mois apres le debut du traitement par febuxostat. L’efficacite, la tolerance et la variation de la fonction renale ont ete analysees. Resultats Nous avons inclus 73 patients goutteux (âge moyen 70,2 ± 11,8 ans, 61 hommes, 31 patients avec nephrangiosclerose et 18 patients transplantes renaux) provenant de 10 centres universitaires. L’uricemie a l’initiation etait de 9,86 ± 2,85 mg/dL, la duree devolution moyenne de la goutte etait de 6,2 ± 7,0 ans. Les comorbidites etaient constituees d’insuffisance cardiaque (17,8 %), d’hypertension arterielle (98,6 %), de diabete (30,1 %), de dyslipidemie (64,8 %) et d’antecedents d’evenements thromboemboliques (38,4 %). Lors de la derniere visite (suivi moyen de 68,5 ± 64,8 semaines), la dose de febuxostat etait de 40 mg/j pour 7 patients (10,5 %), 80 mg/j pour 50 (74,6 %) et 120 mg/j pour 10 patients (14,9 %). L’uricemie etait Conclusion Le febuxostat semble etre efficace chez les patients goutteux insuffisants renaux chroniques stades 4/5. Cependant, la tolerance concernant la fonction renale n’est pas certaine. De plus grandes etudes sont necessaires pour la determiner.

Background Septic spondylodiscitis is an infection involving intervertebral disc and adjacent vertebral endplates that could lead to neurological complications. Magnetic resonance imaging (MRI) is the main imaging modality to suspect spondylodiscitis. However, MRI features predictive for septic spondylodiscitis are still lacking. Objectives To assess the MRI features associated with microbial pathogen detection by CT-guided biopsy among patients with suspected septic spondylodiscitis. Methods Between May 2007 and July 2017, we retrospectively analysed patients who underwent MRI and CT-guided biopsy for suspicion of septic spondylodiscitis. Baseline clinical and biological characteristics were collected. MRIs were analysed by one physician blinded to clinical data. The following MRI features were assessed when available: oedema or contrast-enhancement of intervertebral disk, adjacent vertebrae, epidural and paravertebral space, presence of abscess and paravertebral oedema size. A positive biopsy was defined by pathogen identification on culture or by direct microscopy examination. Results Fifty-one patients (54.9% of males, mean ±SD age of 59.2±19.1 years) were analysed. Lumbar spine (n=38) was the most affected site. A total of 26 (51%) patients had a CT-guided biopsy positive for a bacterial pathogen, mainly mycobacterium tuberculosis (n=7) and staphylococcus aureus (n=7). Disc size reduction, more than 50% of endplate oedema, loss of intradiscal cleft and abscess were the MRI findings associated with detection of bacterial pathogen by biopsy with a frequency of 100%, 92%, 81% and 50%, respectively. Size of paravertebral oedema was statistically higher in positive CT-guided biopsy than those negative (20.5±12.6 vs. 11.0±9.8 mm, p=0.004). The highest specific MRI finding for bacterial pathogen detection was the presence of paravertebral abscess (80%). Conclusions Our study showed that loss of intradiscal cleft, abscess and a large endplate oedema were the best predictive factors for a positive CT-guided biopsy. Size of paravertebral oedema is also associated with detection of bacterial pathogen. Physician must be aware of these MRI findings to better determine which patients should have a CT-guided biopsy. Disclosure of Interest None declared

Objectives To evaluate the performance of MRI inflammatory lesions suggestive of axSpA for the axSpA recognition Methods Observational cross-sectional national multicentre study. Patients: a) Recent onset axSpA patients: first, a sample of 100 patients representative in terms of imaging abnormalities of the global DESIR recent onset axSpA cohort were selected. b) Recent onset CBP patients: consecutive in- and outpatients consulting for recent (>3 months but Results A total of 98 patients with recent onset CBP were included, and compared to 100 recent onset axSpA patients. Age and gender were comparable (mean (SD) 36.2 (9.9) vs. 32.2 (8.7)y, and 41.8% and 45% males, in the CBP vs. axSpA groups, respectively). MRI inflammatory lesions of the SIJ were quite frequent in the CBP group (25% patients with at least one inflammatory lesion) but were significantly more frequently observed in the axSpA group (table 1), with a mean SIJ - SPARCC score of 4.9 (8.8) vs. 0.6 (1.3), p Conclusions ASAS definition of a positive MRI-sacroiliitis performed very well for axSpA recognition; however, definitions proposed for a positive MRI-spine suggestive of axSpA did not seem to perform adequately in this recent disease stage. This supports the idea of not including a positive MRI of the spine in the ASAS classification criteria. Disclosure of Interest None declared

Objectives To evaluate the performances of MRI (SIJ and Spine) structural lesions suggestive of axSpA for its recognition. Methods Observational cross-sectional national multicentre study. Patients: a) Recent onset axSpA patients: first, a sample of 100 patients representative in terms of imaging abnormalities of the global DESIR recent onset axSpA cohort based on the results of the previously published central reading of baseline films of DESIR were selected. b) Recent onset CBP patients: consecutive in- and outpatients consulting for recent mechanical CBP, initiating before the age of 45 y and with a maximum age of 50 y, in four tertiary care Hospitals were included in the study. Imaging: MRI scans (T2-STIR and T1 sequences) of the SIJ and cervico-thoracic and thoraco-lumbar spine were performed in both groups with identical protocol. Central reading: an experienced reader (AM) centrally read all MRI scans, blinded for clinical diagnosis. Statistical analysis: prevalence of lesions suggestive of axSpA was compared in both groups. Sensitivity, specificity and positive likelihood ratio (LR+) of each lesion were calculated. Results A total of 98 patients with recent onset CBP were included, and compared to 100 recent onset axSpA patients. Age and gender were comparable (mean (SD) 36.2 (9.9) vs. 32.2 (8.7)y, and 41.8% and 45% males, in the CBP vs. axSpA groups, respectively). Prevalence of chronic lesions of the SIJ was significantly greater in the axSpA group. Presence of at least 3 subchondral bone erosions at the SIJ performed the best for axSpA discrimination. Prevalence of chronic lesions of the spine was comparable in the two groups. The presence of at least 5 fatty lesions was the most discriminant, with high specificity. Conclusions Presence of at least 3 erosions at the MRI-SIJ and at least 5 fatty lesions at the MRI-spine seemed to performed well for axSpA recognition. Disclosure of Interest None declared

Background Calcium pyrophosphate (CPP) deposition is a frequent joint disease with increased prevalence in older people in whom treatment of acute CPP arthritis with conventional therapies such as colchicine, corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDs) could be contraindicated or not used at an optimal dose. As recommended in gout, anakinra might represent an alternative treatment for acute arthritis. In contrast, the relevance of anakinra in acute CPP arthritis has not given much attention. Objectives We further aimed to analyse the efficacy and safety of anakinra in acute CPP arthritis in a large cohort. Methods We retrospectively included all patients receiving anakinra for acute CPP arthritis between January 2011 and 2017. Medical history data were collected including hypertension, diabetes mellitus, cardiovascular disease, history of gastroduodenal ulcer, renal impairment and concomitant treatments including anticoagulants or antiplatelet drugs. The following data were collected before and 4 days after the first anakinra injection: swollen joint count (SJC), tender joint count (TJC), pain score on a visual analogue scale (VAS, 0–100 mm) and C-reactive protein (CRP) level. A good response was defined according the evaluation of the physician or documentation in the chart of the phrase “good response” after anakinra treatment. Results We included 33 patients (24 women; mean age 79.2±12.8 years). Mean duration of acute arthritis 13.2±12.9 days. CPP arthritis was confirmed by the presence of CCP crystals in synovial fluid in 28/33 (84.8%) patients. For the remaining 5 patients, the diagnosis was confirmed by CPP deposition features seen on imaging. Corticosteroids, NSAIDs and colchicine were previous treatments, without significant improvement in 12 (36.4%), 7 (21.2%) and 18 (54.5%) patients, respectively. The mean dose of corticosteroids was 20.8±8.2 mg/day. Among the 33 patients, 32 had a documented visit at day 4. The number of good responders was 27 (81.8%). At day 4, patients showed decreased mean VAS pain score (from 64.8±26.5 to 21.2±19.7 mm, p Conclusions Our results suggest that anakinra could be a relevant alternative for managing acute CPP arthritis, leading to rapid relief of inflammatory symptoms, with a good tolerance. Disclosure of Interest None declared

OBJECTIVES Onset of primary SS is usually between 40 and 60 years of age, with severe systemic complications in 15% of cases. We sought to determine whether early-onset disease is related to a specific phenotype and if it is predictive of a poor outcome. METHODS Biological and clinical data from 393 patients recruited in the ASSESS cohort, a French multicentre prospective cohort, were compared according to age at diagnosis. RESULTS Fifty-five patients had early-onset disease, defined as age ⩽35 years at diagnosis, and presented a significantly higher frequency of salivary gland enlargement (47.2% vs 33.3%, P = 0.045), adenopathy (25.5% vs 11.8%, P = 0.006), purpura (23.6% vs 9.2%, P = 0.002) and renal involvement (16.4% vs 4.4%, P = 0.003). They had a higher frequency of hypergammaglobulinaemia (60.8% vs 26.6%, P < 0.001), RF positivity (41.5% vs 20.2%, P < 0.001), low C3 level (18.9% vs 9.1%, P = 0.032), low C4 level (54.7% vs 40.2%, P = 0.048) and autoantibodies [84.6% with anti-SSA vs 54.4% (P < 0.001) and 57.7% with anti-SSB vs 29.7% (P < 0.001)]. The change in ESSDAI scores between baseline and the 5-year follow-up was significantly different (P = 0.005) with a trend for worsening in the early-onset group (0.72, P = 0.27) and a significant improvement in the later onset group (-1.27, P < 0.0001). CONCLUSION Early-onset primary SS is associated with a specific phenotype defined by clinical and biological features known to be predictive factors of severe systemic disease. Interestingly, we showed a different evolution of the ESSDAI score depending on the age at disease onset, patients with early-onset disease tending to worsen over time.

Calcium pyrophosphate (CPP) deposition is a frequent joint disease with increased prevalence in older people in whom treatment of acute CPP arthritis with conventional therapies such as colchicine or non-steroidal anti-inflammatory drugs could be contraindicated or not used at an optimal dose. As recommended in gout, anakinra might represent an alternative treatment for arthritis. We aimed to analyze the efficacy and safety of anakinra in acute CPP arthritis in a large reported series. We retrospectively included all patients receiving anakinra for acute CPP arthritis between January 2011 and 2017. The following data were collected before and 4 days after the first anakinra injection: swollen joint count (SJC), tender joint count (TJC), pain score on a visual analog scale (VAS, 0–100 mm), and C-reactive protein (CRP) level. A good response was defined according the evaluation of the physician. We included 33 patients (24 women; mean age 79.2 ± 12.8 years). The number of good responders was 27 (81.8%). At day 4, patients showed decreased mean VAS pain score (from 64.8 ± 26.5 to 21.2 ± 19.7 mm, p

Body mass index (BMI) might affect rheumatoid arthritis (RA) outcomes. Clinical assessment of swollen joint count (SJC) might also be affected by obesity in terms of obesity-related excess adipose tissue. In this study, we compared ultrasonography (US) and clinical examination in assessing the effect of BMI on RA disease activity assessment.This was a single-centre study including RA (ACR/EULAR criteria) patients. US assessment was performed by one trained rheumatologist blinded to clinical data. US synovitis was defined as grey-scale score ≥2 and/or power Doppler score ≥1. The primary outcome measure was difference in SJC (ΔSJC) between clinical and US assessment (US-clinical examination). The secondary outcome was to evaluate the difference between clinical and US assessment of the Disease Activity Score in 28 joints (ΔDAS28) in the 3 BMI subgroups according to the WHO classification.We included 76 RA patients (mean age 53.8 ± 11.8 years; 67% female). Overall, 28 (36.8%), 33 (43.4%) and 15 (19.7%) were normal weight, overweight and obese, respectively. Baseline characteristics did not differ between the 3 BMI subgroups. US-determined SJC was significantly higher than clinical-determined SJC for overweight and obese RA patients: p=0.001 and p=0.049, respectively. The DAS28 was higher with US than clinical examination within the overweight group only (p=0.002). One-way analysis of variance (ANOVA) revealed a significant difference between ΔDAS28 among the 3 BMI subgroups (p=0.046).In high BMI RA patients both SJC and DAS28 seem to be undervalued by clinical assessment when compared to US.

Tumour necrosis factor alpha (TNFα) is a key cytokine in inflammatory rheumatic diseases but is also implicated in multiple sclerosis (MS) where TNFα is elevated in demyelinating plaques. However, TNFα inhibitors (TNFi) have opposite effects: they have revolutionised the treatment of chronic rheumatic diseases but may cause flares of MS.1 Several studies have suggested an association between TNFi use and occurrence of demyelinating disorders.2 3 Their incidence is estimated up to 4% after 18 months of treatment in a recent prospective study with systematic neurological examination before and after treatment initiation.4 In addition, two TNF receptor superfamily 1 ( TNFRSF1A ) single nucleotide polymorphisms, (SNPs) rs1800693 and rs4149584 (TNFRSF1A R92Q), have been shown to increase the risk of developing MS.5 The rs1800693*G allele leads to a dysfunctional TNFα soluble receptor that inhibits TNFα signalling.6 Rare variants of TNFRSF1A locus have also been implicated …

International audience; BACKGROUND: Given the phenotypic similarities between rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) (hereafter, RA-ILD) and idiopathic pulmonary fibrosis, we hypothesized that the strongest risk factor for the development of idiopathic pulmonary fibrosis, the gain-of-function MUC5B promoter variant rs35705950, would also contribute to the risk of ILD among patients with RA. METHODS: Using a discovery population and multiple validation populations, we tested the association of the MUC5B promoter variant rs35705950 in 620 patients with RA-ILD, 614 patients with RA without ILD, and 5448 unaffected controls. RESULTS: Analysis of the discovery population revealed an association of the minor allele of the MUC5B promoter variant with RA-ILD when patients with RA-ILD were compared with unaffected controls (adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.8 to 5.2; P=9.7x10(-17)). The MUC5B promoter variant was also significantly overrepresented among patients with RA-ILD, as compared with unaffected controls, in an analysis of the multiethnic case series (adjusted odds ratio, 5.5; 95% CI, 4.2 to 7.3; P=4.7x10(-35)) and in a combined analysis of the discovery population and the multiethnic case series (adjusted odds ratio, 4.7; 95% CI, 3.9 to 5.8; P=1.3x10(-49)). In addition, the MUC5B promoter variant was associated with an increased risk of ILD among patients with RA (adjusted odds ratio in combined analysis, 3.1; 95% CI, 1.8 to 5.4; P=7.4x10(-5)), particularly among those with evidence of usual interstitial pneumonia on high-resolution computed tomography (adjusted odds ratio in combined analysis, 6.1; 95% CI, 2.9 to 13.1; P=2.5x10(-6)). However, no significant association with the MUC5B promoter variant was observed for the diagnosis of RA alone. CONCLUSIONS: We found that the MUC5B promoter variant was associated with RA-ILD and more specifically associated with evidence of usual interstitial pneumonia on imaging. (Funded by Societe Francaise de Rhumatologie and others.).

Resume Objectifs Des etudes anterieures ont montre que la positivite des anticorps anti-CCP etait predictive d’une bonne reponse au rituximab (RTX) au cours de la polyarthrite rhumatoide (PR). Une approche quantitative de cette hypothese pourrait constituer une methode de choix pour definir un sous-groupe de patients ayant le plus de chance de repondre au RTX. Nous avons donc etudie si le taux serique des anticorps anti-CCP etait predictif de la reponse au MTX chez les patients atteints de PR. Methodes Il s’agissait d’une etude retrospective incluant les patients atteints de PR traites par RTX. Le critere d’evaluation principal etait une baisse du DAS28 superieure a 1,2 a 6 mois (M6). Les criteres secondaires de jugement etaient une bonne reponse et une remission selon les criteres de l’EULAR. Les facteurs predictifs de reponse ont ete testes par une analyse de regression logistique multivariee. Resultats Dans notre etude, ont ete inclus 114 patients atteints de PR (81,6 % de femmes ; mediane d’âge 53,5 ans [IQR 45,7–61,2] ; mediane de l’anciennete de la PR 8,5 ans [4,0–16,0]). Les anticorps anti-CCP etaient positifs chez 93 patients (81,6 %) et la mediane du titre serique des anticorps anti-CCP etait de 583 U/mL [195–1509]. Au total, une baisse du score DAS28 superieure a 1,2 a M6 a ete observee chez 44 patients (38,6 %). En analyse univariee, un titre eleve d’anticorps anti-CCP etait associe a la reponse au RTX plutot qu’a l’absence de reponse a M6 (mediane 1122 [355–1755] vs 386 [149–800] U/mL ; p = 0,0191). En analyse de regression multivariee, en choisissant une valeur seuil de 1000 U/mL, un titre d’anticorps anti-CCP superieur ou egal a 1000 etait associe avec la baisse du DAS28 > 1,2 (OR = 5,10 [1,97–13,2] ; p = 0,0002), avec une bonne reponse EULAR (OR = 4,26 [1,52–11,95] ; p = 0,0059), et avec une tendance a la remission EULAR (OR = 2,52 [0,78–8,12] ; p = 0,1207). Conclusions Un titre eleve d’anticorps anti-CCP est predictif de la reponse au RTX au cours de la PR. Ce facteur, facilement accessible en pratique clinique, peut aider a la realisation d’une medecine personnalisee en selectionnant les meilleurs candidats au traitement par le RTX.

OBJECTIVE The aim of this study was to compare the prevalence of lumbar spondylolisthesis (SPL) in patients suffering from low back pain (LBP) with or without rheumatoid arthritis (RA) and to identify potential factors associated with SPL in patients with RA. METHODS We performed a case-control study. Cases and control patients had chronic LBP (more than 4 weeks). Patient with RA fulfilled the 2010 ACR/EULAR criteria. The main outcome was the presence of lumbar SPL on lumbar X-ray. The prevalence of SPL between RA and control patients was compared using chi-squared test. Potential factors associated with SPL in patients with RA were investigated by univariate and multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS A total of 67 cases and 83 controls were included. Median [interquartile range] age of patients with RA was 60.0 years [51.0-72.0]; 80.6% were females; and 92.5% and 83.6% were positive for anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor, respectively. Mean RA disease duration was 11.2 ± 8.7 years. SPL was more frequent in patients with RA than controls (41.8% versus 18.1%, P = 0.001). Adjusted to gender, RA was associated with increased prevalence of SPL (OR 3.15 [95% CI 1.48-6.70], P = 0.003). Among patients with RA, SPL was mainly Grade 1 (85.7%). Multivariate analysis revealed SPL is associated with increased age in patients with RA (OR 1.06 [1.02-1.11], P = 0.004). CONCLUSION In a population of patients with chronic LBP, the prevalence of lumbar SPL was higher with than without RA. SPL might be explained by synovitis of lumbar facet joints.

International audience; Objectives - The allopurinol dose is limited in chronic kidney disease, particularly stage 4/5 chronic kidney disease. Febuxostat has a hepatic metabolism and has been approved without dose adaptation in gouty patients with stage 1-3 chronic kidney disease. We aimed to study the safety and efficacy of febuxostat for stage 4/5 chronic kidney disease. Methods - In this retrospective study, we included patients with (1) a diagnosis of gout, (2) febuxostat treatment, (3) estimated glomerular filtration rate≤30mL/min/1.73m (Modification of Diet in Renal Disease formula) at febuxostat initiation and (4) follow-up for at least 3 months after febuxostat initiation. Efficacy, safety and variation in estimated glomerular filtration rate were analyzed. Results - We included 73 patients (mean age 70.2±11.8, 61 men, 31 with vascular chronic kidney disease and 18 renal transplantation) with gout (baseline serum uric acid level=9.86±2.85mg/dL, mean gout duration 6.2±7.0 years) from 10 academic centers. Comorbidities included cardiac failure (17.8%), hypertension (98.6%), diabetes mellitus (30.1%), dyslipidemia (64.8%) and history of cardiovascular events (38.4%). At the last visit (mean follow-up 68.5±64.8 weeks), the daily dose of febuxostat was 40mg for 7 patients (10.5%), 80mg for 50 (74.6%) and 120mg for 10 (14.9%). Serum uric acid level was

We aimed to compare the prevalence of enthesopathy seen on ultrasonography (US) in spondyloarthritis (SpA) and rheumatoid arthritis (RA) and compared it to healthy controls.All included patients with RA (2010 ACR/EULAR criteria) and SpA (ASAS criteria) and healthy controls underwent clinical and US evaluation of enthesis at seven sites (quadriceps, proximal and distal patellar, Achilles and triceps tendons, plantar aponeurosis and lateral epicondyle enthesis). The Glasgow Ultrasound Enthesitis Scoring System (GUESS) and the Madrid Sonographic Enthesitis Index (MASEI) scores were determined by two sonographers blinded to clinical data.We included 30 patients with RA (mean age: 55.7±14.8 years, mean disease duration 10.5±7.9years); 41 with SpA (mean age: 45.3±15.4 years, mean disease duration 9.2±8.7years) and 26 healthy controls (HC) (mean age: 50.4±17.3years). Patients with SpA and RA had similar prevalence of painful enthesis of examined sites (17% vs. 14%, non-significant [ns]), but more than among in healthy controls (3%, P0.05 for RA and SpA comparison). Comparison between SpA and RA patients revealed that at least one US enthesis abnormality was found with similar frequency (46% and 48% sites [ns]) but both rheumatic diseases had higher frequency of US enthesis abnormality than HC (31%, P0.05 for RA and SpA comparison). The mean MASEI score was 8.5±7.3 for RA patients, 7.8±6.5 for SpA patients (ns) and 3.4±2.8 for healthy controls (P0.05 for RA and SpA comparison). Overall, 6 RA (20%) and 4 SpA (10%) patients had a MASEI score≥18 (ns). None of the healthy controls had a MASEI score≥18 (P0.05 for RA and SpA comparison). The mean GUESS score was 5.8±3.1 and 6.3±3.9 for RA and SpA patients (ns), and 4.0±3.1 for healthy controls (P0.01 vs. SpA and0.05 vs. RA).RA and SpA patients did not differ in entheseal abnormalities seen on US. Such US features may have low specificity in inflammatory conditions affecting joints and enthesis such as SpA and RA.

Arthritis secondary to invasive meningococcemia is rare and has been described as a direct result of bacteremia or as immunoallergic-type arthritis, related to the immune complex. Only a few case series have been reported. This multicenter study aimed to describe the clinical characteristics and therapeutic outcomes of arthritis secondary to meningococcal infection. We performed a 5-year retrospective study. We included all patients with inflammatory joint symptoms and proven meningococcal disease defined by the identification of Neisseria meningitidis in blood, cerebrospinal fluid, or synovial fluid. Septic arthritis was defined by the identification of N meningitidis in joint fluid. Immune-mediated arthritis was considered to be arthritis occurring after at least 1 day of invasive meningococcal disease without positive joint fluid culture. A total of 7 patients (5 males) with joint symptoms and meningococcal disease were identified. The clinical presentation was mainly oligoarticular and the knee was the most frequent joint site. Five patients had septic arthritis and 4 had immune-mediated arthritis; 2 had septic arthritis followed by immune-mediated arthritis. Immune-mediated arthritis occurred 3 to 7 days after meningococcal meningitis, and treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) led to improvement without complications. Physicians must be vigilant to the different clinical presentations in patients with arthritis associated with invasive meningococcal disease. If immune-mediated arthritis is suspected, NSAIDs are usually efficient.

Background An interferon (IFN) signature is involved in the pathogenesis of primary Sjogren9s syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. Objectives To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies. Methods The genetic study involved 673 patients with pSS from 2 French pSS cohorts and 585 healthy French controls. Functional studies were performed on sorted monocytes, stimulated or not. IL-12A mRNA and IL-12 and IL-35 protein levels were assessed by qRT-PCR and by ELISA and a multiplex kit for IL-35 and IL-12, respectively. Results We confirmed the association of the IL-12A rs485497 polymorphism and pSS and found an increased serum protein level of IL-12p70 in pSS patients carrying the risk allele (p=0.016). Serum level of IL-12p70 was greater in patients than controls (p=0.0001), especially patients with more active disease (p=0.05); conversely IL-35 level was decreased in patients (p=0.0001) especially in patients with a more active disease (p=0.05). Conclusions Our findings emphasize the involvement of the IL-12/IL-35 balance in the pathogenesis of pSS. Serum IL-35 level was associated with low disease activity, in contrast to serum IL-12p70 level, which was rather associated with a more active disease. Acknowledgements We thank Dr Odile Devergne (Universite Paris Descartes, AP-HP, Hopital Necker, Paris) for her expertise on the IL-35 ELISA kit to ensure the quality and reproducibility of this test. The authors thank the following investigators of the ASSESS cohort prospective cohort of patients with Sjogren9s syndrome (all in France) who recruited the patients and conducted follow-up: A. L. Fauchais (Limoges), S. Rist (Orleans), V. Le Guern (Paris), G. Hayem (Paris), J. Sibilia (Strasbourg), J. Morel (Montpellier), A. Saraux (Brest), A. Perdriger (Rennes), X. Puechal (Le Mans), E Hachulla (Lille) and V. Goeb (Rouen). The authors thank Dr J. Benessiano, S Tubiana and all staff members of the Bichat Hospital Biological Resource Center (Paris) for their help in centralizing and managing biologic data collection from the French ASSESS, Disclosure of Interest None declared

Background Despite its high prevalence and mortality, little is known about the pathogenesis of RA–associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA–ILD frequently share the usual interstitial pneumonia pattern and common environmental risk factors, we hypothesized that the two diseases may share additional risk factors including FPF-linked genes. Objectives Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD. Methods We used whole-exome sequencing (WES) followed by restricted analysis of a discrete number of FPF-linked genes and performed a Burden test to assess the excess number of mutations in RA–ILD patients compared to controls. Results Among the 101 RA–ILD patients included, 12 (11.9%) had 13 WESidentified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA–ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations for RA–ILD patients (p=9.45’10-4, odds ratio [OR] 3.17 95% CI 1.53 – 6.12). Telomeres were shorter for RA-ILD patients with a TERT, RTEL1 or PARN mutation than controls (p=2.87x10-2). Conclusions Our results support the contribution of FPF-linked genes to RA–ILD susceptibility. Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and composed of two subtypes, limited and diffuse cutaneous forms. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Objectives To expand the list of susceptibility genes and deepen biological insights for SSc. Methods We performed trans-ethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4,436 cases and 14,751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighboring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. Results We identified two significant SNP in two loci, GSDMA and PRDM1 , both of which are related with immune functions and associated with other autoimmune diseases (p=1.4x10 -10 and 6.6x10 -10 , respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3 . PRDM1 encodes BLIMP1, a transcription factor regulating T cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighboring genes, and this could explain the association in this locus. We found different HLA association patterns between the two populations or two subtypes. Enrichment analysis suggested the importance of CD4 naive primary T cell. Conclusions GSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc. Disclosure of Interest None declared

Background The gold standard for diagnosis of calcium pyrophosphate (CPP) deposition (CPPD) is the identification of CPP crystals in synovial fluid. However, aspiration of synovial fluid can be challenging in small joints such as the wrist, a usual location of arthritis in CPPD. Despite its low sensitivity, the most widely used imaging modality is conventional radiography but ultrasound (US) seems a useful tool for diagnosis of CPPD. Objectives We aimed to compare the performance of US and conventional radiography of the wrist for diagnosis of CPPD. Methods Patients with joint effusion (knee, hip, shoulder, ankle or wrist) were consecutively included. CPPD was diagnosed by CPP crystals identified in synovial fluid. Patients without CPP crystals in synovial fluid were controls. As recommended, we used the term chondrocalcinosis (CC) to assess imaging features suggesting CPPD. Two blinded operators assessed CC in all patients by US and conventional radiography of the wrist. The presence of CC in triangular fibrocartilage (TFC) and wrist hyaline cartilage in US and TFC and radiocarpal (RC) joint in radiography was noted. A patient was considered to have CC if at least one wrist had imaging features of CC. Results We included 58 patients with joint effusion (32 with CPPD). The remaining 26 patients, controls, had rheumatoid arthritis (n=13), spondyloarthritis (n=6), gout (n=6), and osteoarthritis (n=1). The mean age was 67.1±16.3 years. Location of joint effusion was as follows: 34 knees, 15 wrists, 3 shoulders, 2 ankles, 3 hips and 1 elbow. Among CPPD patients, US revealed CC in 30 (93.7%) and radiography in 17 (53.1%) (p Conclusions Our study suggests that wrist US should be considered a relevant tool for the diagnosis of CPPD, with higher sensitivity than radiography. Disclosure of Interest None declared

Background Introduction of the biologic therapies has dramatically improved the outcome of severe rheumatoid arthritis (RA). Biologic therapies play a central role in the control of synovial inflammation. However they also decrease host defenses leading to an increased rate of infection. Because of their adverse effects, a careful assessment is needed before their initiation. A systematic assessment of dental or sinus infection before a biologic therapy is not required. Objectives The aim of our study was to assess the prevalence and the usefulness of a systematic screening of oral (dental and/or sinus) infection of RA patients before biologic therapy initiation. Methods This was a monocentric retrospective study. We included RA (ACR/EULAR 2010 criteria) patients with active disease despite disease-modifying anti-rheumatic drugs (DMARDs) and requiring biologic therapy initiation between 2010 and 2016. The following parameters were collected: demographic and disease characteristics, disease activity (C-reactive protein, disease activity score (DAS) 28), currents therapies (DMARDS, corticosteroids). Dental infection was assessed by stomatologist after clinical and panoramic dental X- ray evaluation. Sinusitis was defined on sinus computed tomography as partial or complete opacification of one or more sinus cavities. Factors associated with oral infections were analyzed in uni- and multivariate models. Results We included 223 RA patients (79.4% of female, mean ± SD disease duration of 8.9±8.6 years). The mean age was 54±10.9 years, 70.8% rheumatoid factor (RF) positive, 84.4% anti–citrullinated protein antibody (ACPA) positive and 68.1% had radiographic damages. The mean DAS 28 was 5.5±2.6; 71% of patients received corticosteroids (mean 7mg per day of equivalent prednisone) and 63% methotrexate (mean 17.8mg per week). No patient had pain or other sinus or dental symptoms. Before biologic agent initiation, systematic dental and sinus screening revealed an oral infection in 31.5% of patients (dental: 20.2% and sinus: 14.8%). In univariate analysis, active smoking was associated with a higher risk of oral infection (OR=2.16 [1.02–4.57], p=0.038) and methotrexate with a lower rate (OR=0.43 [0.23–0.81], p=0.006). Corticosteroid, disease duration, DAS 28, RF, ACPA and structural damages were not associated with oral infection. No significant association was confirmed with oral infection using multivariate analysis. Conclusions In our study, one third of RA patients requiring biologic agents had asymptomatic oral infection. The high prevalence of oral infection in RA patients suggests the usefulness of systematic dental and sinus screening before biologic therapy initiation. Disclosure of Interest None declared

Background Ultrasonography (US) has demonstrated its ability to detect urate deposition in gouty patients. Some US features have been suggested to be specific such as tophus and the double contour (DC) sign. In contrast to the usefulness of US for diagnosis, data are lacking on its role in follow-up of gout deposition after initiation of urate-lowering therapy (ULT). Objectives We aimed to determine the ability of US to show disappearance of urate deposits in gouty patients requiring ULT. Methods We performed a 6-month multicentre prospective study. To be included in the study, patients needed to have: i) a proven gout (identification of monosodic urate crystal in synovial fluid analysis or tophus aspiration), ii) presence of US features of gout (tophus and/or DC sign) at knee and/or first metatarsophalangeal joints (MTP1s). Serum uric-acid (SUA) level was assessed at baseline, M3 and M6. US evaluations were performed at baseline, M3 and M6 after starting ULT, by one local rheumatologist, blinded to SUA levels and clinical data. The primary outcome was the decrease (absolute value and percentage of decrease) of US tophus after 6 months of ULT, according to the final SUA levels. The secondary outcome was the mean percentage of joint sites with DC sign disappearance. Three stages of SUA levels were defined (high SUA levels: >360 μmol/l, low SUA: 300 -360 μmol/l, very low SUA: Results A total of 79 gouty patients (mean ± SD age 61.8±14 years, 91% of males) were included. The mean disease duration was 6.3±6.1 years. Tophi were found at clinical exam in 29% of patients. Baseline SUA levels were 530±97 μmol/l. At least one US tophus and DC sign were found in 74 (93.7%) and 68 (86.1%) of patients, respectively. Allopurinol and febuxostat was started in 26 (33%) and 53 (67%) patients, respectively. A total of 67 patients were completers at 6 months. Among those M6 completers, 39 and 18 patients achieved a very low and low SUA levels, respectively. The 10 remaining patients maintained high SUA levels. Comparison of US features of gout modifications between the 3 groups of final SUA levels revealed a higher decrease of US tophus size and higher proportion of DC sign dissolution among patients with lowest SUA levels (Table 1). Additionally, final M6 SUA levels was associated with: decrease size of tophus (r=0.5093 [0.3012; 0.6711], P Conclusions US is able to detect decrease or disappearance of US urate deposits after ULT. Additionally, the decrease of US deposits is strongly correlated with lowest SUA levels. These data suggest that US could be useful for ULT management in gouty patients. Disclosure of Interest None declared

Objective To determine risk factors for primary Sjogren's syndrome (SS)-associated lymphoma in a multicenter cohort of patients, with analysis of the predictive power of previously reported risk factors, including the presence of ectopic germinal center (GC)-like structures in minor salivary gland (MSG) biopsy tissue. Methods One hundred fifteen patients with primary SS were included, and MSG biopsy tissue from these patients was retrospectively examined, focusing on the presence of ectopic GC-like structures. Epidemiologic, clinical, biologic, immunologic, and histologic data were collected at the time of diagnosis of primary SS. Patients with non-Hodgkin's lymphoma (NHL) were compared with those without NHL during the follow-up period, using a Cox proportional hazards multiple regression model. Results NHL was diagnosed in 8 patients (6.96%), and ectopic GC-like structures in 19 patients (16.5%). The presence of ectopic GC-like structures was associated with a 7.8-fold increased risk of lymphoma occurrence (95% confidence interval [95% CI] 1.73-34.86 [P = 0.0075]). Other independent predictors included a positive cryoglobulin test result (hazard ratio [HR] 7.10, 95% CI 1.74-28.92 [P = 0.006]), male sex (HR 28.73, 95% CI 4.46-144.87 [P = 0.0004]), sensorimotor neuropathy (HR 35.48, 95% CI 5.79-217.39 [P = 0.0001]), and splenomegaly (HR 19.9, 95% CI 4.4-90 [P = 0.0001]). Conclusion The presence of ectopic GC-like structures in MSG biopsy tissue is associated with the risk of lymphoma in patients with primary SS. These data reinforce the major role of MSG biopsy tissue in primary SS, for the identification a priori of a subgroup of patients with the highest risk of lymphoma.

Ultrasound (US) seems a useful tool for diagnosis of calcium pyrophosphate (CPP) deposition (CPPD). We aimed to compare the performance of US and conventional radiography of the wrist for diagnosis of CPPD.Patients with CPP crystals identified in synovial fluid (SF) (knee, hip, shoulder, ankle or wrist) were consecutively included and compared to patients without CPP crystals in synovial fluid considered as controls. As recommended, we used the term chondrocalcinosis (CC) to assess imaging features suggesting CPPD. In all patients, US and radiographic assessment of CC of the wrists was performed by two distinct operators blinded each other (one operator by imaging modality). The two operators were blinded to clinical data, SF analysis and US or radiography findings.We included 32 CPPD patients and 26 controls. Among CPPD patients, US revealed CC in 30 (93.7%) and radiography in 17 (53.1%) (P0.001). The sensitivity and specificity of US for the diagnosis of CPPD were 94% and 85%, respectively; the positive likelihood ratio (LR+) was 6.1. The sensitivity and specificity of radiography were 53.1% and 100%, respectively. At joints level independently of SF analysis, US revealed CC in 35 joints without radiographic CC whereas X-rays showed CC in 3 joints without US CC. The κ coefficient between US and radiography for CC was moderate: 0.33 (0.171-0.408).Our study suggests that wrist US should be considered as a relevant tool for the diagnosis of CPPD, with higher sensitivity than radiography for detecting CPP deposits.

ObjectivesSystemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases.MethodsWe performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighbouring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes.ResultsWe identified two significant SNP in two loci, GSDMA and PRDM1, both of which are related to immune functions and associated with other autoimmune diseases (p=1.4×10−10 and 6.6×10−10, respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3. PRDM1 encodes BLIMP1, a transcription factor regulating T-cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighbouring genes, and this could explain the association in this locus. We found different human leukocyte antigen (HLA) association patterns between the two populations. Enrichment analysis suggested the importance of CD4-naïve primary T cell.ConclusionsGSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc.

Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53–6.12; p=9.45×10−4). Telomeres were shorter in RA-ILD patients with a TERT, RTEL1 or PARN mutation than in controls (p=2.87×10−2).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility.

International audience

Resume Objectif Le but de cette etude etait de determiner la capacite de l’echographie a mettre en evidence la diminution ou la disparition des depots d’urates chez les patients goutteux recevant un traitement hypouricemiant. Methodes Afin d’etre inclus dans cette etude prospective monocentrique, les patients devaient (1) avoir une goutte prouvee sur la base de la presence de cristaux d’urates monosodiques (UMS) dans le liquide synovial et (2) avoir des depots echographiques d’urates (signe du double contour et/ou tophus) avant l’introduction d’un traitement hypouricemiant (allopurinol [ n = 4], febuxostat [ n = 12]). A l’inclusion et 6 mois plus tard, un echographiste entraine avait evalue les genoux et les premieres metatarsophalangiennes (MTP1). L’uricemie etait evaluee a l’inclusion, a 3 mois et a 6 mois de l’introduction du traitement. La correlation entre les donnees echographiques et l’obtention de l’objectif en termes de baisse de l’uricemie ( Resultats Nous avons etudie 16 patients (tous de sexe masculin, âge moyen 61,0 ± 18,3 ans). La duree moyenne d’evolution de la maladie etait de 7,1 ± 6,2 ans. Les tophus etaient retrouves a l’examen clinique chez 56 % des patients. L’uricemie de base etait de 688 ± 153 μmol/L. A l’inclusion, l’echographie avait retrouve des tophus ou un double contour chez 62,5 % et 75 % des patients pour les genoux et 87,5 % pour les MTP1. A 6 mois du traitement hypouricemiant, aucun des 4 patients n’ayant pas atteint l’objectif de baisse de l’uricemie n’avait une disparition des signes echographiques. Parmi les 12 patients restants, les caracteristiques echographiques (tophus ou double contour) avaient disparu ou avaient diminue chez tous les patients sauf un qui avait un double contour au niveau de l’une des MTP1. La correlation entre l’aspect echographique global et l’uricemie etait excellente (κ = 0,875). Conclusions L’echographie doit montrer la disparition des depots d’urates apres un traitement hypouricemiant et semble bien correlee a l’efficacite des traitements.

Objective Previous studies reported that anti-CCP antibody positivity predicts good response to rituximab (RTX) in rheumatoid arthritis (RA). A quantitative approach to such possibility could be a good way to detect the subset of patients most likely to respond. We investigated whether serum anti-CCP antibody titres could predict response to RTX in RA patients. Methods We retrospectively investigated RA patients who received RTX. The primary criterion was decrease in DAS28 > 1.2 at 6 months (M6). Secondary efficacy criteria included a good response and remission according to EULAR. Predictors of response were investigated by multivariate logistic regression analysis. Results We included 114 RA patients (81.6% female, median age 53.5 [IQR 45.7–61.2] years, median disease duration 8.5 [4.0–16.0] years). Anti-CCP antibodies were present in 93 patients (81.6%), with median anti-CCP antibody titres 583 [195–1509] U/mL. In all, 44 patients (38.6%) showed decreased DAS28 > 1.2 at M6. On univariate analysis, high anti-CCP titres were associated with response rather than non-response to RTX (median 1122 [355–1755] vs. 386 [149–800] U/mL, P = 0.0191) at M6. On multivariate regression analysis, with a cut-off of 1000 U/mL, anti-CCP antibody titres ≥ 1000 was associated with a decrease in DAS28 > 1.2 (OR 5.10 [1.97–13.2], P = 0.0002); a EULAR good response (4.26 [1.52–11.95], P = 0.0059); and a trend for EULAR remission (2.52 [0.78–8.12], P = 0.1207). Conclusion High anti-CCP antibody titres predict response to RTX in RA. This factor, easily assessed in clinical practice, can help with personalized medicine and selecting the best candidates for RTX treatment.

Resume Objectifs Determiner l’impact des polymorphismes nucleotidiques simples (SNP) dans les genes IL-2RA (rs2104286) et IL-2RB (rs743777 et rs3218253) sur les risques d’erosion chez les patients atteints de polyarthrite rhumatoide (PR). Methodes Ce travail derive de deux cohortes prospectives de PR precoce : les cohortes ESPOIR (n = 439) et RMP (n = 180). Les proportions de patients avec erosion au depart et a un an en fonction des genotypes de l’IL-2RA (rs2104286) ou des haplotypes generes par les deux SNP de l’IL-2RB ont ete comparees dans la population totale et chez les patients positifs pour les ACPA. Une meta-analyse determinant le risque erosif en fonction des haplotypes des deux SNP de l’IL-2RB a ete realisee en utilisant la methode de Mantel-Haenszel. Un modele multivarie a ete utilise afin de determiner l’effet independant des haplotypes d’IL-2RB sur le risque erosif. Resultats L’haplotype AC d’IL-2RB etait associe de maniere significative avec les taux d’erosion chez les patients positifs pour les ACPA dans la cohorte ESPOIR (taux d’erosion : AC/AC : 78 % contre GC ou GT/GC ou GT : 44 %, p = 0,001). Une meta-analyse des cohortes ESPOIR et RMP a confirme que le fait de porter l’haplotype AC etait significativement associe au taux d’erosion a un an dans la population totale (OR [IC95 %] = 1,92 [1,14–3,22], p = 0,01) et chez les patients ACPA-positifs (OR [IC95 %] = 3,34 [1,68–6,67], p = 0,0006). Un modele multivarie dans la cohorte ESPOIR a demontre l’effet independant de l’haplotype AC (6,03 [1,94–18,69], p = 0,002) sur le risque erosif chez les patients ACPA-positifs. Conclusion Un haplotype forme par deux SNP localises dans le gene IL-2RB etait associe a l’etat erosif dans la PR precoce.

Resume Introduction Les epaules sont souvent atteintes dans la spondyloarthrite (SpA) et dans la polyarthrite rhumatoide (PR). Le diagnostic de spondyloarthrite peripherique et le diagnostic differentiel avec une polyarthrite rhumatoide sont parfois difficiles. Une etude recente a demontre que l’echographie des mains pouvait differencier le rhumatisme psoriasique de la polyarthrite rhumatoide. Le but de cette etude etait de comparer les caracteristiques echographiques entre la SpA, la PR et les sujets sains. Methodes Un total de 38 patients avec SpA et 43 PR avec une atteinte clinique des epaules ont ete inclus et compares a 33 sujets sains. Un rhumatologue avait effectue un examen echographique, en aveugle des renseignements cliniques. Les parametres suivants ont ete evalues : epanchement gleno-humeral, tenosynovite du long biceps, bursite sous-acromio-deltoidienne, synovite acromio-claviculaire (AC) et erosion osseuse humerale. Resultats Trente-huit SpA (âge moyen : 49,9 ± 15,4 ans, 58 % d’hommes), 43 PR (52,9 ± 16,6 ans, 26 % d’hommes) et 33 temoins (55,2 ± 16,9 ans, 42 % d’hommes) ont ete evalues. En comparaison avec la PR, les patients atteints de SpA etaient plus frequemment atteints de synovite AC (66 % versus 5 %, p Conclusion Nos resultats suggerent que l’atteinte des AC est hautement evocatrice de SpA chez les patients se plaignant de douleurs inflammatoires des epaules. L’echographie permet d’aider au diagnostic positif de SpA et au diagnostic differentiel avec une PR.