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Objectives To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life. Methods A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case–control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease. Results Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5–7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14–0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD. Conclusion The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died.

Resume Objectif Proposer des recommandations pour une utilisation pertinente de l’echographie dans la polyarthrite rhumatoide (PR) en pratique quotidienne, fondees sur les donnees de la litterature et l’opinion d’experts en echographie osteo-articulaire. Methodes A partir d’une analyse systematique de la litterature, un comite scientifique a selectionne des thematiques et questions pertinentes pour elaborer une premiere version des recommandations. Celles-ci ont ete soumises a un groupe d’experts en echographie osteo-articulaire selon une procedure Delphi, permettant l’elaboration d’une version preliminaire des recommandations qui ont ensuite ete reformulees et validees par un groupe d’experts elargi en evaluant leur pertinence, leur comprehensibilite et leur exhaustivite, au cours d’une reunion presentielle. Le degre d’accord des experts et la faisabilite de ces recommandations en pratique ont ete precises. Resultats A l’issue de 2 tours de Delphi, un consensus a ete obtenu sur 3 principes generaux, incluant les definitions des sites articulaires, tendineux et osseux a evaluer, et 10 recommandations. Elles soulignent l’interet de l’echographie pour aider au diagnostic de PR devant des arthralgies inflammatoires ou une oligoarthrite inclassee et pour evaluer l’etendue de l’atteinte inflammatoire et structurale initialement. Elles positionnent cet examen au cours du suivi et une fois la remission clinique obtenue avant d’envisager la decroissance therapeutique. Elles precisent son interet pour aider a la realisation des gestes techniques. Conclusion Ces 10 recommandations consensuelles devraient permettre une homogeneisation ainsi qu’une optimisation des pratiques cliniques, conduisant a ameliorer la prise en charge des patients presentant une PR.

Resume Objectif Proposer une liste de variables a collecter des le diagnostic et tout au long du suivi des patients atteints de spondyloarthrite axiale (SpA axiale) pour optimiser leur prise en charge en routine. Methodes Le processus s’est deroule en plusieurs etapes : (1) estimation de l’interet de 51 variables proposees pour l’evaluation de la SpA axiale via une recherche systematique dans la litterature ; (2) consensus de 78 rhumatologues hospitaliers ou de ville notant chaque variable selon un bareme de 4 points de « Peu utile/Inutile » a « Indispensable » ; (3) consensus sur la frequence minimale d’evaluation des variables selectionnees selon un bareme de 5 points allant de « A chaque consultation » a « Jamais systematiquement ». Resultats La recherche systematique a identifie 14 133 resumes dont 213 ont ete inclus dans la synthese qualitative finale. Les donnees a collecter lors du bilan systematique initial comprenaient cinq questionnaires patient auto-administres, trois variables de l’entretien avec le medecin, deux variables de l’examen physique, deux variables de l’imagerie specifique a la SpA axiale et deux autres examens. La collecte systematique a ete recommandee a chaque visite pour deux variables, deux fois par an pour une variable, une fois par an pour six variables et tous les deux ans pour une variable. Conclusions Cette initiative a utilise des approches fondees sur des preuves et sur un consensus d’experts pour definir un ensemble de base de variables a collecter et a consigner immediatement apres le diagnostic et pendant le suivi de routine des patients atteints de SpA axiale.

Resume Introduction Dans la sclerodermie systemique, peu d’etudes ont montre que l’echographie de la main et du poignet est plus sensible que l’examen clinique pour la detection des synovites et tenosynovites. Encore, moins d’etudes ont evalue l’atteinte echographique du pied et la cheville en echographie. Nos objectifs etaient de decrire la prevalence echographique des synovites et des tenosynovites des mains et des pieds chez des patients atteints de sclerodermie systemique selon les criteres ACR/EULAR 2013 et analyser leurs correlations avec les caracteristiques de la maladie et le handicap de la main. Methodes Des patients consecutifs atteints de sclerodermie systemique selon les criteres ACR/EULAR. 2013 etaient inclus dans une etude transversale monocentrique. Ils beneficiaient d’un examen clinique standardise et d’une echographie musculosquelettique des mains et des pieds. Des donnees cliniques, biologiques et d’imagerie etaient collectees. Resultats Au total, 55 patients ont ete inclus. L’echographie etait plus sensible que l’examen clinique pour detecter au moins une synovite (respectivement 52 % contre 25 %, p = 0,025) et au moins une tenosynovite (respectivement 16 % contre 4 %, p = 0,009). 18 % des patients presentaient une tenosynovite de cheville et 29 % une synovite de cheville ou du pied, principalement localisee aux articulations metatarsophalangiennes (25,5 %). Avoir au moins une synovite des mains en echographie etait associee a un indice fonctionnel de la main de Cochin plus eleve (moyenne 25 ± 3 contre 12 ± 2, p = 0,003) et a la forme cutanee diffuse (p = 0,038). Conclusion Notre etude montre que l’echographie est superieure a l’examen clinique pour detecter les synovites et les tenosynovites dans la sclerodermie systemique. L’atteinte du pied est moins frequente que celle des mains, elle est presente dans un quart des cas, principalement localisee aux metatarsophalangiennes. Enfin avoir une synovite de la main est associee aux formes cutanees diffuses et a un handicap de la main plus eleve.

Background Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular (CV) disease. Adiponectin is involved in the metabolism of glucose and lipids with favourable effects on CV disease, especially its high molecular weight (HMW) isoform. Body composition changes are described in RA with various phenotypes including obesity. The effects of tocilizumab on serum adiponectin and body composition, especially fat mass, in patients with RA are not well determined. Methods Patients with active RA despite previous csDMARDs and/or bDMARDs and who were tocilizumab naïve were enrolled in a multicentre open-label study. They were evaluated at baseline, 1, 3, 6 and 12 months. Clinical assessment included body mass index (BMI) and anthropometric measurements. Lipid and metabolic parameters, serum adiponectin (total and HMW), leptin, resistin and ghrelin were measured at each time point. Body composition (lean mass, fat mass, % fat, fat in the android and gynoid regions) was evaluated at baseline, 6 and 12 months. Results One hundred seven patients were included. Both total and HMW adiponectin significantly increased from baseline to month 3, peaking respectively at month 3 (p = 0.0105) and month 1 (p p = 0.001). BMI and waist circumference significantly increased at month 6 and 12, as well as lean mass at month 6 (p = 0.0097). Fat mass, percentage fat and android fat did not change over the study period. Lipid parameters (total cholesterol and LDL cholesterol) increased while glycaemia, insulin and HOMA-IR remained stable. Serum leptin, resistin and ghrelin did not change during follow-up. Conclusions Tocilizumab treatment in RA patients was associated with a significant increase in total and HMW adiponectin, especially at the onset of the treatment. Tocilizumab also induced a significant gain in lean mass, while fat mass did not change. These variations in adiponectin levels during tocilizumab treatment could have positive effects on the CV risk of RA patients. In addition, tocilizumab may have an anabolic impact on lean mass/skeletal muscle. Trial registration The ADIPRAT study was a phase IV open-label multicentre study retrospectively registered on ClinicalTrials.gov under the number NCT02843789 (date of registration: July 26, 2016).

To evaluate the impact of a nurse-led program of systematic screening for the management (detection/prevention) of comorbidities.Prospective, randomized, controlled, open, 12-month trial (NCT02374749).consecutive patients with axial Spondyloarthritis (axSpA) (according to the rheumatologist) THE PROGRAM: A nurse collected data on comorbidities during a specific outpatient visit. In the event of non-agreement with recommendations, the patient was informed and a specific recommendation was given to the patient (orally and in a with a detailed written report). Patients were seen after one year in a nurse-led visit. TREATMENT ALLOCATION: random allocation (i.e. either this program or an educational program not presented here and considered here as the control group).change after one year of a weighted comorbidity management score (0 to 100 where 0= optimal management).502 patients were included (252 and 250 in the active and control groups, respectively): age: 47±12 years, male gender: 63%, disease duration: 14±11y. After one year, no differences were observed in a weighted comorbidity management score. However, the number of patients in agreement with recommendations was significantly higher in the active group for vaccinations (flu vaccination: 28.6% vs. 9.9%, p0.01; pneumococcal vaccination:40.0% vs. 21.1%,p=0.04), for cancer screening (skin cancer screening: 36.3% vs. 17.2%, p=0.04) and for osteoporosis (bone densitometry performed: 22.6% vs. 8.7%, p0.01; Vitamin D supplementation initiation: 51.9% vs. 9.4%, p0.01).This study suggests the short-term benefit of a single-visit nurse-led program for systematic screening of comorbidities for its management in agreement with recommendations, even in this young population of patients with axSpA.

Resume La calprotectine est une proteine de liaison au calcium exprimee au site inflammatoire par les neutrophiles et les monocytes afin d’activer le systeme immunitaire inne. Grâce a cette caracteristique unique, elle constitue un bon indicateur de l’inflammation locale dans les rhumatismes inflammatoires chroniques. L’ensemble des donnees met en evidence le role cle que joue la calprotectine dans le processus inflammatoire de plusieurs rhumatismes inflammatoires. L’interet des dosages de calprotectine serique ou plasmatique a ete largement etudie ces dernieres annees, en particulier dans la polyarthrite rhumatoide, la spondyloarthrite, l’arthrite juvenile idiopathique et les vascularites associees aux ANCA. La calprotectine a ete identifiee comme un biomarqueur performant qui permet d’evaluer et de suivre l’activite de la maladie mais egalement de predire l’evolution structurale ou la reponse au traitement. La calprotectine a montre son interet dans la prediction de la progression radiologique dans la polyarthrite rhumatoide et la spondylarthrite ankylosante. La calprotectine est egalement un biomarqueur predictif du risque de rechute dans les vascularites associees aux ANCA et de maladie inflammatoire de l’intestin dans les spondyloarthrites. Neanmoins, les etudes rapportent des resultats contradictoires qui necessitent d’etre confirmes dans de plus larges cohortes. L’absence de standardisation du dosage de calprotectine rend difficile la reproduction des resultats et la comparaison entre les differentes etudes. Dans cette revue, nous discutons de l’interet de la calprotectine dans les rhumatismes inflammatoires chroniques en tant que biomarqueur diagnostique, d’activite ou pronostique.

Resume L’echographie en rhumatologie s’est developpee a partir des annees 1990, a la fois pour le diagnostic et le suivi therapeutique, mais aussi dans le developpement de techniques infiltratives echoguidees. Depuis, son utilisation fait partie du quotidien du rhumatologue. Ce chapitre permet de passer en revue les differents aspects des gestes echoguides en rhumatologie : les principales indications, les contre-indications et les effets indesirables a connaitre, ainsi que les modalites pratiques : l’aspect technique et les voies d’abord et le choix du materiel (derives cortisones, aiguilles, sondes).

Resume Les infiltrations rachidiennes lombaires sont de pratique courante mais l’evaluation de leur efficacite est rendue difficile de par l’heterogeneite des etudes. Le radioguidage avec utilisation de produit de contraste reste la reference meme si l’echo-assistance a quelques indications. L’utilisation des produits cortisones a fait l’objet de recommandations de societes savantes au vu de rares accidents graves decrits dans la litterature. Les voies d’abord seront largement decrites avec leurs avantages et leurs inconvenients. Les indications sont majoritairement representees par les contraintes radiculaires discales ou osseuses et les symptomes lies a un dysfonctionnement zygapophysaire. Les rachis operes necessitent des precautions dans les indications et les realisations des gestes mais la encore des recommandations ont ete emises.

Resume L’utilisation des infiltrations repose en rhumatologie et en traumatologie du sportif sur l’utilisation des glucocorticoides (GC) et/ou des acides hyaluroniques (AH). Le niveau de preuve de leur efficacite ainsi que leur place dans la strategie therapeutique dans l’arthrose ou les tendinopathies reste debattu malgre leur large utilisation. Depuis peu de temps, les injections locales de plasma enrichi en plaquettes autologues (PRP) sont utilisees et provoquent les memes interrogations que les autres injections locales. En effet, differents types de PRP peuvent etre obtenus. Ils sont classes selon le taux de concentration plaquettaire, le contenu en leucocytes et la presence d’un activateur plaquettaire externe. La variete de leur composition est susceptible d’entrainer une variation de leurs effets biologiques demontres in vitro ou chez l’animal (anti-inflammatoire, anti-apoptotique…). Plusieurs meta-analyses concernant des essais randomises et controles avec PRP ont ete recemment publiees. Elles ont globalement mis en evidence des effets antalgiques et fonctionnels qui persistaient jusqu’a 12 mois. L’effet taille est leger a modere, mais pertinent cliniquement, surtout dans la gonarthrose et l’epicondylalgie laterale. Ces effets sont au moins equivalents a ceux des GC et des AH avec une tolerance similaire a celui des AH. Ces donnees recentes de la litterature suggerent que les PRP ont un rapport benefice risque favorable et qu’ils pourraient etre utilises lorsqu’une indication d’infiltration est posee, dans la gonarthrose et l’epicondylalgie en particulier. Des etudes ulterieures sont necessaires pour preciser leurs mecanismes antalgiques et leur effet chondroprotecteur a plus long terme dans la gonarthrose.

International audience; ObjectivesRheumatoid arthritis (RA) is a debilitating disease, but patient management and treatment have been revolutionized since the advent of bDMARDs. However, about one third of RA patients do not respond to specific bDMARD treatment without clear identified reasons. Different bDMARDs must be tried until the right drug is found. Here, we sought to identify a predictive protein signature to stratify patient responsiveness to rituximab (RTX) among patients with an insufficient response to a first anti-TNFα treatment.MethodsSerum samples were collected at baseline before RTX initiation. A proteomics study comparing responders and nonresponders was conducted to identify and select potential predictive biomarkers whose concentration was measured by quantitative assays. Logistic regression was performed to determine the best biomarker combination to predict good or nonresponse to RTX (EULAR criteria after 6 months’ treatment).ResultsEleven biomarkers potentially discriminating between responders and nonresponders were selected following discovery proteomics. Quantitative immunoassays and univariate statistical analysis showed that fetuin-A and thyroxine binding globulin (TBG) presented a good capacity to discriminate between patient groups. A logistic regression analysis revealed that the combination of fetuin-A plus TBG could accurately predict a patient’s responsiveness to RTX with an AUC of 0.86, sensitivity of 80%, and a specificity of 79%.ConclusionIn RA patients for whom a first anti-TNFα treatment has failed, the serum abundance of fetuin-A and TBG before initiating RTX treatment is an indicator for their response status at 6 months. ClinicalTrials.gov identifier: NCT01000441.

In 1954, brown trout were introduced to the Kerguelen archipelago (49°S, 70°E), a pristine, sub-Antarctic environment previously devoid of native freshwater fishes. Trout began spreading rapidly via coastal waters to colonize adjacent watersheds, however, recent and unexpectedly the spread has slowed. To better understand the ecology of the brown trout here, and why their expansion has slowed, we documented the marine habitat use, foraging ecology, and environmental conditions experienced over one year by 50 acoustically tagged individuals at the colonization front. Trout mainly utilized the marine habitat proximate to their tagging site, ranging no further than 7 km and not entering any uncolonized watersheds. Nutritional indicators showed that trout were in good condition at the time of tagging. Stomach contents and isotope signatures in muscle of additional trout revealed a diet of amphipods (68%), fish (23%), isopods (6%), and zooplankton (6%). The small migration distances observed, presence of suitable habitat, and rich local foraging opportunities suggest that trout can achieve their resource needs close to their home rivers. This may explain why the expansion of brown trout at Kerguelen has slowed.

Studies on the effects of dual tasking in patients with chronic inflammatory rheumatic diseases are limited. The aim of this study was to assess dual tasking while walking in patients with axial spondyloarthritis (axSpA) in comparison to healthy controls. Thirty patients with axSpA and thirty healthy controls underwent a 10-m walk test at a self-selected comfortable walking speed in single- and dual-task conditions. Foot-worn inertial sensors were used to compute spatiotemporal gait parameters. Analysis of spatiotemporal gait parameters showed that the secondary manual task negatively affected walking performance in terms of significantly decreased mean speed (p p p = 0.008) and increased double support (p = 0.002) and stance time (p = 0.008). No significant interaction of group and condition was observed. Both groups showed lower gait performance in dual task condition by reducing speed, swing time and stride length, and increasing double support and stance time. Patients with axSpA were not more affected by the dual task than matched healthy controls, suggesting that the secondary manual task did not require greater attention in patients with axSpA. Increasing the complexity of the walking and/or secondary task may increase the sensitivity of the dual-task design to axial spondyloarthritis.

Introduction La question de la survenue de maladies inflammatoires chroniques de l’intestin (MICI) de novo (MICI-DN) sous inhibiteurs de l’interleukine 17 (anti-IL 17) a ete soulevee a partir des donnees des essais pivots. Les objectifs principaux de l’etude MISSIL (Maladies Inflammatoires chroniques de l’Intestin SouS anti-IL 17) etaient de decrire les cas de MICI-DN sous anti-IL17 en France, d’identifier d’eventuels facteurs de risque et d’evaluer l’incidence des MICI-DN chez les patients (pts) sous anti-IL 17 en France. Patients et methodes Un registre national collectant les cas de MICI-DN chez les pts sous anti-IL 17 a ete mis en place entre 2016 et 2019 sous l’egide du CRI, du GETAID et de ResoPso. Une etude cas-temoins a ete realisee avec 2 temoins apparies sur l’âge (±8 ans), le sexe et la pathologie. Les comparaisons des cas aux temoins ont ete realisees grâce a des modeles lineaires mixtes generalises. Une regression logistique conditionnelle a ete utilisee en cas d’echec de la convergence des modeles lineaires mixes en incluant les blocs apparies comme effet aleatoire. Les taux d’incidence annuels de MICI-DN (en 100 pts-annees [PA]) ont ete calcules a partir du nombre de cas annuels declares de MICI-DN au numerateur, et le nombre annuel de PA sous anti-IL 17 (chiffres fournis par l’industrie pharmaceutique) au denominateur. Resultats 31 cas de MICI-DN sous secukinumab (SEK) ont ete recueillis entre janvier 2016 et decembre 2019 : 27 pts ayant une spondyloarthrite et 4 ayant un psoriasis. Aucun cas n’a ete declare sous ixekizumab. L’âge moyen etait de 49,2 ± 14,6 ans. 14/31 etaient des femmes, 10/25 avaient une sacro-iliite radiographique (SI-Rx) et 15/25 une sacro-iliite IRM (SI-IRM). Seuls 4 pts etaient naifs de biotherapies. Le delai median de survenue des symptomes de MICI-DN etait de 4,0 (1,5-7,5) mois apres initiation du SEK. Les symptomes principaux etaient la diarrhee et la perte de poids. La CRP mediane a la survenue des symptomes etait de 68,0 (34,0-177,5) mg/L. Les traitements recus apres arret du SEK (chez tous les pts) etaient : une corticotherapie chez 19 pts, un anti-TNFα chez 21 pts, l’ustekinumab chez 7 pts et la colectomie chez 2 pts, 3 pts ayant recu plusieurs biotherapies. L’evolution etait favorable pour 29/31 pts avec une remission (17/31), une amelioration (7/31) ou une stabilisation (5/31), 2 pts etant decedes : un infarctus massif du myocarde dans un contexte de denutrition majeure liee a la MICI-DN et deces des suites de la colectomie. L’incidence des MICI-DN etait calculee a 0,69 % (7/1010) en 2016, de 0,23 % (11/4704) en 2017, 0,11 % (7/6550) en 2018 et 0,08 % (6/7951) en 2019. Dans l’etude cas-temoins, la presence d’une SI-RX (OR = 0,65, IC95 % 0,45-0,94, p = 0,022), un antecedent de traitement par etanercept (ETN) (OR = 0,33, IC95 % 0,14-0,80, p = 0,014) et un nombre eleve de lignes de biotherapies anterieures (OR = 0,57, IC95 % 0,36-0,92, p = 0,021) etaient significativement associes a une moindre survenue de MICI-DN. L’association avec une SI-IRM tendait a la significativite (OR= 0,62, IC95 % 0,38-1,02, p = 0,059). Conclusion Dans cette etude nationale de vraie vie, la survenue d’une MICI-DN sous anti-IL 17 est rare, avec une incidence faible, proche de celle rapportee dans la litterature pour des patients atteints de spondyloarthrite et non traites par anti-IL 17 (0,2 %) [1] . De plus cette incidence annuelle diminue regulierement de 2016 a 2019. Dans l’etude cas-temoins, la presence d’un antecedent de traitement par ETN peut etre un facteur confondant (ETN prescrit souvent chez des pts pour lesquels une MICI associee a ete eliminee).

Resume Le lavage articulaire consiste a evacuer et laver du compartiment intra-articulaire les facteurs pro-inflammatoires et les produits de degradation du cartilage articulaire. Nous decrirons les modalites techniques utilisant une ou deux voies ainsi que les produits utilises. Nous rapporterons les indications principales : la gonarthrose avec hydarthrose recidivante, les arthrites septiques et non septiques chroniques. Il parait bien exister dans certaines conditions une efficacite justifiant la poursuite de sa pratique.

Calprotectin is a calcium binding protein produced by neutrophils and monocytes locally at the site of inflammation in order to trigger the innate immunity receptors. This unique characteristic makes it a good proxy for evaluation of local inflammation in chronic inflammatory rheumatic diseases. Complete data suggest, in inflammatory rheumatic diseases, a relevant role of calprotectin in the inflammatory process. The interest of serum or plasma calprotectin dosage has been studied intensively, in the current years, especially in rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis and ANCA associated vasculitis. Calprotectin seems to be a great candidate as biomarker to assess and monitor disease activity, to predict structural progression or response to the treatment. Calprotectin showed its ability to predict radiological progression in rheumatoid arthritis and ankylosing spondylitis. Serum calprotectin can predict the risk of relapse in ANCA associated vasculitis and the risk of inflammatory bowel disease in spondyloarthritis. Nevertheless, studies report controversial result requiring replication in other large cohort. The lack of assay standardization between studies is a problem to replicate and compare studies. In this review, we discuss on the interest of systemic calprotectin in chronic inflammatory rheumatic disease as a diagnostic, activity or prognostic biomarker.

Resume Les hopitaux de jour de rhumatologie ont principalement developpe leur activite avec l’arrivee des biotherapies administrees par voie intraveineuse. Avec l’apparition d’autres voies d’administrations, ils ont etendu leur activite a diverses typologies de prise en charge. Les textes encadrant la tarification des hopitaux de jour laissent des ambiguites d’interpretation, responsables d’une application heterogene entre etablissements et d’une insecurite financiere. Ceci genere une inadequation entre les besoins des patients et les lieux et modalites de prise en charge. En 2017, de nouveaux vecteurs de facturation ont ete introduits pour accompagner la coordination pluriprofessionnelle autour de la maladie chronique, mais plusieurs freins empechent leur mise en place. Pour contribuer au developpement d’une rhumatologie ambulatoire proposant des prises en charge plus adaptees, le premier enjeu est de se saisir de ces nouveaux vecteurs de tarifications. Pour cela il conviendrait de penser de nouvelles structures de soins adaptees au parcours du patient pour l’accueil de toutes les venues sans nuitees, et de s’aider de reunions tripartites entre medecins rhumatologues, medecins du departement d’information medicale et controle de gestion afin d’organiser les parcours presentant un equilibre medicoeconomique. Ce travail est le point de depart pour une reflexion encore plus poussee dans un environnement qui doit faire face a de nombreux enjeux. Le cadre experimental propose par l’article 51 de la Loi de Financement de la Securite Sociale pour 2018 est ainsi une opportunite de tester de nouveaux modeles de prise en charge, comme une remuneration periodique de suivi des patients.

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease affecting predominantly sacroiliac joints and axial skeleton. axSpA progression being irregular and hardly predictable, identifying functional decline is particularly important in patient with axSpA to allow delivery of timely and targeted interventions. Pain, reduced range of motion or altered posture can have adverse consequences on gait. Although gait has previously been used as a sensitive measure of physical outcomes in elderly and pathological populations, to the best of our knowledge, no study has used gait as a predictor of physical function in patients with axSpA. The objective of our study is hence to determine if gait parameters measured in patients with axSpA could predict the evaluation at 18 months of physical function as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI). This is a prospective and longitudinal study. Sixty patients with axSpA and 30 healthy age- and sex-matched controls will be included. Patients should be aged 18–65 years at time of their first evaluation, followed at Grenoble Alpes University Hospital for axSpA or ankylosing spondylitis, able to walk 180 m without technical help and with stable treatment for at least 12 months. Clinical characteristics, BASFI, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), clinical and laboratory measurements of gait will be assessed during four visits (at baseline and at months 6, 12, and 18). Similar assessments will be performed once for the healthy control group. A linear mixed model at 6, 12 and 18 months will be constructed to answer to the first objective, with the BASFI as dependent variable and gait parameters as explanatory variables. The data collection started in August 2018 and will be completed with the inclusion and follow-up of all the participants. We believe that the combination of clinical and laboratory measurements of gait in patients with axSpA could strengthen the capacity to monitor disease’s evolution and to predict changes in patients’ physical function. Results of the present study could ultimately allow delivering targeted, timely, personalized interventions and treatment in patients with axSpA. Trial registration: The study was approved by local ethic committee (CPP Ile De France 1, RCB: 2017-A03468-45, date of agreement: July 17th, last version: V4.0, 2018, March 5th, 2019) and is retrospectively registered in Clinical trials (NCT03761212).

Objective We aimed to determine whether calprotectin and α-defensins could discriminate septic from other inflammatory arthritides. Methods Synovial fluids with a predominance of neutrophils from patients with septic arthritis, pseudogout and RA were prospectively collected. Neutrophil-related proteins calprotectin and human neutrophil α-defensins levels were assessed in synovial fluids. Demographic parameters and biomarkers with P-value ⩽0.05 for differentiating septic from non-septic arthritis were included in a multivariable model. Multivariable logistic regression with stepwise selection was performed to build the final combined model. Results A total of 74 patients were included: septic arthritis (n = 26), pseudogout (n = 28) and RA (n = 20). Patients with septic arthritis were more likely to be male and young, and to display higher synovial neutrophil count. Calprotectin was significantly increased in patients with septic arthritis. The multivariable model included calprotectin, synovial fluid neutrophil count and gender. Calprotectin was the only biomarker that discriminated septic arthritis from non-septic inflammatory arthritides, with 76% sensitivity, 94% specificity and a positive likelihood ratio = 12.2 at the threshold for calprotectin of 150 mg/l. Conclusion Synovial fluid calprotectin is a relevant biomarker to discriminate septic arthritis from other inflammatory arthritides. This biomarker should be tested in an independent cohort.

Axial Spondyloarthritis (ax-SpA) is associated with increased risk of cardiovascular disease (CVD)-specific deaths. We aimed to assess the prevalence of left ventricular (LV) systolic and diastolic dysfunction and valvular heart disease (VHD) by transthoracic echocardiography (TTE) in ax-SpA patients without history of CVD.A systematic literature review was performed in PUBMED, Embase, Cochrane Library databases published before April 2020. We included all controlled studies assessing myocardial function and heart valve by TTE in ax-SpA without history of CVD. A meta-analysis was performed with random or fixed effects model estimating mean differences (MD) and odds ratio (OR).Literature search selected 189 abstracts and 28 articles were included (1471 ax-SpA and 1115 controls). ax-SpA had a statistically slight alteration of LV ejection fraction (MD=0.64%, 95%CI: 0.14-1.14). ax-SpA had more frequently LV diastolic dysfunction (OR=3.43, 95%CI: 1.78-6.59) and an alteration of E/A ratio (MD=0.15, 95%CI: 0.08-0.21), deceleration time (MD=13.07ms, 95%CI: 7.75-18.40), isovolumetric relaxation time (MD=7.90ms, 95%CI: 4.50-11.30), left-ventricular end diastolic (MD=0.57mm, 95%CI: 0.19-0.95) and systolic (MD=0.77mm, 95%CI: 0.36-1.17) diameters. Three studies (15%) used a combination of TTE parameters to diagnose LV diastolic dysfunction. Prevalence of mitral regurgitation and aortic regurgitation were similar in ax-SpA patients and healthy individuals.ax-SpA have a non-clinically relevant alteration of LV ejection fraction and similar prevalence of VHD compared to healthy individuals. LV diastolic TTE parameters are altered in ax-SpA. However, most studies do not combine set of parameters to recognize diastolic dysfunction. The clinical relevance of diastolic dysfunction observed by TTE remains to be determined in future longitudinal studies.

Objective The Flare Assessment in RA (FLARE-RA) self-administered questionnaire aims to identify patients who had flare in the interval between two consultations. This study aimed to establish a threshold for FLARE-RA score to identify RA flare. Methods The Tocilizumab SubCutAneous study evaluated the efficacy and safety of s.c. tocilizumab (TCZ) to patients with active RA. Disease activity was assessed with the DAS28ESR at baseline and at week 2 (W2), W4, W12 and W24. The FLARE-RA questionnaire was administered at W12 and W24. Patient satisfaction, assessed at baseline and W24 with the Patient Acceptable Symptom State (PASS), was used as a surrogate marker of no flare. A correlation was sought between the FLARE-RA score at W12 and W24 and the area under the receiver operating characteristic (ROC) curve (AUC) for monthly DAS28ESR. The optimal FLARE-RA cut-off below which patient satisfaction reached the PASS was explored with an ROC curve. Results A total of 139 patients were included (mean age 57.3 ± 13.8 years, 74.1% women, mean RA duration 10.8 ± 9.2 years, mean DAS28ESR 5.8 ± 1.1). The correlation between the FLARE-RA score and DAS28ESR AUC was moderate at all times: ρ = 0.41 at W12 (P < 0.0001) and 0.51 at W24 (P < 0.0001). The optimal cut-off for the FLARE-RA score to identify absence of flare (i.e. an acceptable situation based on the PASS) was 2.3 with an AUC of 0.81. Conclusion FLARE-RA and DAS28ESR assessment differ; we propose a FLARE-RA cut-off of 2.3, below which the situation (i.e. without flare) is acceptable for patients.

BACKGROUND Axial spondyloarthritis (axSpA) can lead to spinal mobility restrictions associated with restricted lower limb ranges of motion, thoracic kyphosis, spinopelvic ankylosis, or decrease in muscle strength. It is well known that these factors can have consequences on spatiotemporal gait parameters during walking. However, no study has assessed spatiotemporal gait parameters in patients with axSpA. Divergent results have been obtained in the studies assessing spatiotemporal gait parameters in ankylosing spondylitis, a subgroup of axSpA, which could be partly explained by self-reported pain intensity scores at time of assessment. Inertial measurement units (IMUs) are increasingly popular and may facilitate gait assessment in clinical practice. OBJECTIVE This study compared spatiotemporal gait parameters assessed with foot-worn IMUs in patients with axSpA and matched healthy individuals without and with pain intensity score as a covariate. METHODS A total of 30 patients with axSpA and 30 age- and sex-matched healthy controls performed a 10-m walk test at comfortable speed. Various spatiotemporal gait parameters were computed from foot-worn inertial sensors including gait speed in ms–1 (mean walking velocity), cadence in steps/minute (number of steps in a minute), stride length in m (distance between 2 consecutive footprints of the same foot on the ground), swing time in percentage (portion of the cycle during which the foot is in the air), stance time in percentage (portion of the cycle during which part of the foot touches the ground), and double support time in percentage (portion of the cycle where both feet touch the ground). RESULTS Age, height, and weight were not significantly different between groups. Self-reported pain intensity was significantly higher in patients with axSpA than healthy controls (Pt tests indicated that patients with axSpA presented lower gait speed (PP=.004), shorter stride length (PPPPPP=.001) and swing time (PPPP=.17). CONCLUSIONS Gait was significantly altered in patients with axSpA with reduced speed, cadence, stride length, and swing time and increased double support and stance time. Taken together, these changes in spatiotemporal gait parameters could be interpreted as the adoption of a so-called cautious gait pattern in patients with axSpA. Among factors that may influence gait in patients with axSpA, patient self-reported pain intensity could play a role. Finally, IMUs allowed computation of spatiotemporal gait parameters and are usable to assess gait in patients with axSpA in clinical routine. CLINICALTRIAL ClinicalTrials.gov NCT03761212; https://clinicaltrials.gov/ct2/show/NCT03761212 INTERNATIONAL REGISTERED REPORT RR2-10.1007/s00296-019-04396-4

Water warming induced by human activities can impact fish larvae survival, notably because it influences larval development and prey abundances. Amphidromous gobies of the subfamily Sicydiinae are particularly sensitive to this threat as the newly hatched free embryos are poorly developed and the first feeding opportunity only occurs after they reach the ocean. Here, we studied how water temperature (21, 23, 25, 29 and 31 degrees C) impacts early development stages of Sicyopterus lagocephalus in both freshwater and marine aquaria (salinity 35). We monitored survival time, larval condition and the occurrence of critical developmental events such as mouth opening, yolk sac and oil globule resorption. In freshwater, the survival exceeded 150 hours at 21 degrees C, while it dropped below 50 hours at 31 degrees C. In seawater, the larval development of unfed larvae was significantly affected by temperature, survival time being greatly reduced in warmer waters. Accounting for the observed duration between mouth opening and the resorption of the oil globule, we estimated that larvae need to find suitable prey in seawater within a short time: around 30 hours during the peak of reproduction in summer. Otherwise, their endogenous reserves become depleted and their condition degrades. This study emphasises the sensitivity of free embryos to stream flow alterations, which contributes to the increase in water temperature and to the slowing down of larvae drift to the ocean. We conclude that once in seawater the temperature and feeding conditions experienced by amphidromous larvae are critical for survival.

Objectives Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation. Methods Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18–37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit. Results A gradual decrease in patients’ serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = –0.27, P = 0.003; CRP: r = –0.16, P = 0.06). Conclusion This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled. ClinicalTrials.gov Identifier NCT03666091.

Objective To propose a list of variables to be collected right after the diagnosis has been made and during the follow-up of patients with axial spondyloarthritis (ax-SpA) for an optimal management in daily practice. Methods The process comprised (1) the evaluation of the interest of 51 variables proposed for the assessment of ax-SpA by means of a systematic literature research; (2) a consensus process involving 78 hospital-based or office-based rheumatologists, considering the collection of each variable in a 4 grade scale from “not very useful/useless” to “mandatory”; (3) a consensus on the minimum interval of time for periodic assessment of the selected variables on a 5 grade scale from “at each visit” to “never to be re-collected”. Results The systematic literature research retrieved a total of 14,133 abstracts, of which 213 were included in the final qualitative synthesis. Data to be collected at the initial systematic review comprised 5 patient's self-administered questionnaires, 3 variables of the physician's interview, 2 variables of the physical examination, 2 variables of the specific ax-SpA imaging and 2 other investigations. Two variables were recommended to be systematically collected at each visit, 1 variable twice a year, 6 variables yearly and 1 variable every 2 years. Conclusions Using an evidence-based and an expert consensus approaches, this initiative defined a core set of variables to be collected and reported right after the diagnosis and during follow-up of patients with ax-SpA in daily practice.

Background Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease-modifying antirheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increased use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one third will not respond to the selected drug. In nonresponse cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or nonresponse to these molecules is currently available. Methods The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a substudy will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study. Discussion This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. Trial registration ClincalTrials.gov NCT04147026. Registered on 31 October, 2019.

Resume La loi francaise autorise les osteopathes et les chiropracteurs, ni medecins ni masseurs-kinesitherapeutes, a pratiquer des manipulations vertebrales sous certaines conditions. Compte-tenu du developpement tous azimuts des soins manuels en France, cet article a pour but de presenter une synthese narrative de litterature sur les manipulations vertebrales pratiquees chez l’adulte dans le traitement des lombalgies non specifiques aigues et chroniques. Quatorze revues systematiques dont dix avec meta-analyses ont ete incluses. Les resultats de ces revues sont souvent contradictoires et decevants d’un point de vue pratique. Les manipulations vertebrales lato sensu ont une efficacite faible avec des effets tres principalement a court terme sur la reduction de la douleur ou l’amelioration des indices algo-fonctionnels dans le traitement des lombalgies. L’heterogeneite des definitions des lombalgies et des manipulations vertebrales est la premiere source de discordance entre auteurs. L’attention devrait etre attiree dans le futur, sur une meilleure evaluation interculturelle des pratiques et plus de recherches integrant des methodologies rigoureuses par sous-groupes repondant a des regles de prediction clinique.

Objectives. Central neurological manifestations of rheumatoid arthritis (RA) like rheumatoid meningitis (RM) are rare, little known and have a high rate of morbi-mortality. METHODS. We described six cases of RM that were directly related to RA activity after exhaustive assessment. RESULTS. They were mainly women, aged of 50 to 69. All were positive for anti-cyclic citrullinated peptide antibodies and half for rheumatoid factors. RA activity, duration, and treatments were heterogeneous including oral steroids, conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs. Symptoms were various, with acute or progressive beginning, main were: generalized or focal seizure (4/6), fever (3/6), headaches (3/6), and frontal syndrome (2/6). Imaging lesions were four leptomeningitis, one pachymeningitis, and one association of both. MRI usually showed hypersignal in various territories in T2-FLAIR (fluid attenuated inversion recovery) mode, and enhancement in T1-weighted mode after gadolinium injection. All patients had lumbar puncture that found sterile cerebrospinal fluid, no neoplasic cell, elevated cell count in 5/6 cases and elevated proteins concentration in 3/6 cases. Cerebral biopsy was possible for three patients, and definitively confirmed the diagnosis of aseptic lepto- or pachymenintis, excluding vasculitis and lymphoma. Different treatments were used like intravenous high dose steroids, immunoglobulins or biologic DMARDs, with variable clinical and imaging outcome: one death, one complete recovery, and four recoveries with sequelae. Conclusions. Clinical symptoms, imaging, lumbar puncture, and serological studies are often nonspecific, only histologic examination can confirm the diagnosis of RM. Any central neurological manifestation in RA patients, even in quiescent and ancient RA, should warn the physician.

ZAP-70SKG, Il17a-deficient SKG, and BALB/c female mice were infected with C muridarum or C muridarum luciferase in the genitals. C muridarum dissemination was assessed by in vivo imaging or genomic DNA amplification. Macrophages were depleted using clodronate liposomes. Anti-tumor necrosis factor (anti-TNF) and anti-interleukin-23p19 (anti-IL-23p19) were administered after infection or arthritis onset. Gene expression of Hspa5, Tgtp1, Il23a, Il17a, Il12b, and Tnf was compared in SKG mice and BALB/c mice.One week following infection with C muridarum, macrophages and neutrophils were observed to have infiltrated the uteri of mice and were also shown to have carried C muridarum DNA to the spleen. C muridarum load was higher in SKG mice than in BALB/c mice. Macrophage depletion was shown to reduce C muridarum load and prevent development of arthritis. Compared with BALB/c mice, expression of Il23a and Il17a was increased in the uterine and splenic neutrophils of SKG mice. The presence of anti-IL-23p19 during infection or Il17a deficiency suppressed arthritis. Tnf was overexpressed in the joints of SKG mice within 1 week postinfection, and persisted beyond the first week. TNF inhibition during infection or at arthritis onset suppressed the development of arthritis. Levels of endoplasmic reticulum stress were constitutively increased in the joints of SKG mice but were induced, in conjunction with immunity-related GTPase, by C muridarum infection in the uterus.C muridarum load is higher in SKG mice than in BALB/c mice. Whereas proinflammatory IL-23 produced by neutrophils contributes to the initiation of C muridarum-mediated ReA, macrophage depletion reduces C muridarum dissemination to other tissues, tissue burden, and the development of arthritis. TNF inhibition was also shown to suppress arthritis development. Our data suggest that enhanced bacterial dissemination in macrophages of SKG mice drives the TNF production needed for persistent arthritis.

Objective To evaluate the impact of a nurse-led program of self-management and self-assessment of disease activity in axial spondyloarthritis. Methods Prospective, randomized, controlled, open, 12-month trial (NCT02374749). Participants were consecutive axial spondyloarthritis patients (according to the rheumatologist) and nurses having participated in a 1-day training meeting. The program included self-management: educational video and specific video of graduated, home-based exercises for patients; and self-assessment: video presenting the rationale of tight monitoring of disease activity with composite scores (Ankylosing Spondylitis Disease activity Score, ASDAS/Bath Ankyslosing Spondylitis Disease Activity Index, BASDAI). The nurse trained patients to collect, calculate and report (monthly) ASDAS/BASDAI. Treatment allocation was by random allocation to this program or a comorbidities assessment (not presented here and considered here as the control group). Results A total of 502 patients (250 and 252 in the active and control groups, respectively) were enrolled (age: 46.7 (12.2) years, male gender: 62.7%, disease duration: 13.7 (11.0) years). After the one-year follow-up period, the adherence to the self-assessment program was considered good (i.e. 79% reported scores >6 times). Despite a lack of statistical significance in the primary outcome (e.g. coping) there was a statistically significant difference in favor of this program for the following variables: change in BASDAI, number and duration of the home exercises in the active group, and physical activity (international physical activity score, IPAQ). Conclusion This study suggests a short-term benefit of a nurse-led program on self-management and self-assessment for disease activity in a young axial spondyloarthritis population in terms of disease activity, exercises and physical activity.

Background: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease modifying anti-rheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increases use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one-third will not respond to the selected drug. In non-response cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or non-response to these molecules is currently available.Methods : The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: Prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: Prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a sub study will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study.Discussion : This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. Trial registration : The study was registered at clincaltrials.gov (NCT04147026). Registered on 31 October, 2019.